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The present study aims to parameterize the numerical models of flat slabs based on five experimental prototypes developed previously. The analyzed slabs had dimensions of 1800 mm × 1800 mm and a thickness of 130 mm. Two slabs did not have openings, and three slabs had stud‐type shear reinforcement. Subsequently, five new slab models were selected with position variations and several openings, with a fixed diameter of 75 mm and without shear reinforcement. After calibration of the models, the following results were obtained: the numerical rupture load approached at least 90% of the experimental rupture load, and the rupture modes and cracking patterns were similar to those observed in the experimental models. When it is impossible to move the column openings vertically, it is more beneficial to position them at the corners of the column rather than close to the same face of the column. Thus, it was possible to numerically analyze the effects of the position and number of openings in flat slabs. [ABSTRACT FROM AUTHOR]

Learning and resolving uncertainty should be important components of management decisions, but not every type of uncertainty is equally important to resolve. For rare, threatened, and endangered species, information may be limited and there is often great urgency to halt potential population declines. Therefore, the most important uncertainties are those that would lead to different decisions intended to improve outcomes for species of interest. The New England cottontail (Sylvilagus transitionalis) is an endemic species to the northeastern United States and is listed as a species of special concern, threatened, or endangered in all states in its current range. States within the historical New England cottontail range have made substantial investments in habitat management, captive breeding, and research, but considerable demographic, management, and monitoring uncertainties remain. Connecticut is the geographic core of the current range of the species and therefore has been the focus of many management efforts, including improving habitat, creating new habitat patches, removing eastern cottontails (Sylvilagus floridanus), and releasing captive‐bred New England cottontails. We used a value of information analysis to identify the optimal management decision given current uncertainty and to evaluate how sources of uncertainty might lead to changes in management decisions. Given the current understanding of the New England cottontail in Connecticut, we identified the optimal management decision as improving existing habitat patches without monitoring for the species and managers could expect a 3.4% increase in populations if decision‐making uncertainty could be fully resolved. Multiple sources of uncertainty influenced results, but variation in New England cottontail density and the response of the species to the removal of eastern cottontails were most likely to result in changes to management decisions. At lower New England cottontail densities, releasing captive‐bred individuals competed with improving habitat as the optimal management action. Accounting for the value of information benefits New England cottontail management by guiding research efforts toward information that is most beneficial for decision‐makers and providing insights into parameter thresholds that would lead to changes in management decisions. [ABSTRACT FROM AUTHOR]

Summary: Peripheral T‐cell lymphomas (PTCLs) are a heterogeneous group of haematological cancers with generally poor clinical outcomes. However, a subset of patients experience durable disease control, and little is known regarding long‐term outcomes. The International T‐cell Lymphoma Project (ITCLP) is the largest prospectively collected cohort of patients with PTCLs, providing insight into clinical outcomes at academic medical centres globally. We performed a long‐term outcome analysis on patients from the ITCLP with available 10‐year follow‐up data (n = 735). The overall response rate to first‐line therapy was 68%, while 5‐ and 10‐year overall survival estimates were 49% and 40% respectively. Most deaths occurred prior to 5 years, and for patients alive at 5 years, the chance of surviving to 10 years was 84%. However, lymphoma remained the leading cause of death in the 5‐ to 10‐year period (67%). Low‐risk International Prognostic Index and Prognostic Index for T‐cell lymphoma scores both identified patients with improved survival, while in multivariate analysis, age >60 years and Eastern Cooperative Oncology Group performance status 2–4 were associated with inferior outcomes. The favourable survival seen in patients achieving durable initial disease control emphasizes the unmet need for optimal front‐line therapeutic approaches in PTCLs. [ABSTRACT FROM AUTHOR]

Reinforced concrete flat slab projects usually require openings close to the columns for electrical and hydraulic installations. Since such openings reduce the punching shear of slabs, a comprehensive study is needed. In this paper, numerical models of slabs tested in literature were elaborated upon, using the commercial software in finite elements DIANA. The physical nonlinearity of the materials was considered. After the calibration and validation of the numerical parameters related to concrete and reinforcement, 62 numerical models were created for performing a parametric analysis. The numerical analysis aimed to study the effect of openings close to the columns and verify the punching resistance reduction. In this parametric study, the main variables were the compressive strength of the concrete, the bending reinforcement ratio, the number of openings, and the distance from the openings to the column's face. Finally, the numerical results obtained were compared with the punching strength values provided by the main structural design codes, viz., NBR 6118 (2014), Eurocode 2 (2004), ACI 318 (2019), fib Model Code (2010), and the next generation of Eurocode 2, which are constantly questioned in academic papers regarding their safety. [ABSTRACT FROM AUTHOR]

Aim: Children have largely been unaffected by severe COVID‐19 compared to adults, but data suggest that they may have experienced new conditions after developing the disease. We compared outcomes in children who had experienced COVID‐19 and healthy controls. Methods: A retrospective nested cohort study assessed the incidence rate of new‐onset conditions after COVID‐19 in children aged 0–14 years. Data were retrieved from an Italian paediatric primary care database linked to Veneto Region registries. Exposed children with a positive nasopharyngeal swab were matched 1:1 with unexposed children who had tested negative. Conditional Cox regression was fitted to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the exposure and outcome associations after adjusting for covariates. Results: We compared 1656 exposed and 1656 unexposed children from 1 February 2020 to 30 November 2021. The overall excess risk for new‐onset conditions after COVID‐19 was 78% higher in the exposed than unexposed children. We found significantly higher risks for some new conditions in exposed children, including mental health issues (aHR 1.8, 95% CI 1.1–3.0) and neurological problems (aHR 2.4, 95% CI 1.4–4.1). Conclusion: Exposed children had a 78% higher risk of developing new conditions of interest after COVID‐19 than unexposed children. [ABSTRACT FROM AUTHOR]

Academic research and the financial industry have recently shown great interest in Machine Learning algorithms capable of solving complex learning tasks, although in the field of firms' default prediction the lack of interpretability has prevented an extensive adoption of the black‐box type of models. In order to overcome this drawback and maintain the high performances of black‐boxes, this paper has chosen a model‐agnostic approach. Accumulated Local Effects and Shapley values are used to shape the predictors' impact on the likelihood of default and rank them according to their contribution to the model outcome. Prediction is achieved by two Machine Learning algorithms (eXtreme Gradient Boosting and FeedForward Neural Networks) compared with three standard discriminant models. Results show that our analysis of the Italian Small and Medium Enterprises manufacturing industry benefits from the overall highest classification power by the eXtreme Gradient Boosting algorithm still maintaining a rich interpretation framework to support decisions. [ABSTRACT FROM AUTHOR]

Much has been published about the harmful effects to humans when they are exposed to mercury (Hg) in environmental media including their diet. Numerous health advisories around the world, including for the South River, Virginia, USA, warn against consumption of Hg‐contaminated fish species. Fewer studies have focused on other dietary sources of Hg and how to advise humans potentially exposed by this route. In undertaking a human health risk assessment for the former DuPont facility in Waynesboro, Virginia, USA, and the nearby South River and surrounding watershed, the available published information on Hg exposure through dietary consumption of nonfish items proved unsuitable for extrapolation purposes. In response, an evaluation of potential Hg exposure to residents who might consume livestock, poultry, and wildlife raised or collected in the South River watershed was conducted to inform the risk‐assessment process. The newly collected data on Hg in these dietary items filled an important data gap, suggesting that there was little concern about limiting dietary consumption for most items. These results were communicated to the public through print and electronic platforms, in the form of "fact sheets." We describe the studies and actions taken to better explain the potential for human exposures to Hg in nonfish dietary items from a portion of the watershed of the South River. Environ Toxicol Chem 2023;42:2237–2252. © 2023 SETAC [ABSTRACT FROM AUTHOR]

This paper proposes a novel method to analyze multidimensional poverty by using a large set of feasible weights to summarize the information about the poor, which enables remaining agnostic about the relative importance given to different poverty dimensions. This method allows for the calculation of the individual probability of being poor in a multidimensional perspective. The distribution of individual probabilities can then be combined with Generalized Lorenz dominance techniques to derive unanimous consent for a wide class of social welfare functions with a minimum load of value judgments. The innovations proposed here allow to move from a dual definition of poverty, where poor and non‐poor individuals are classified in a mutually exclusive context, to a continuous measure of deprivation capturing both the extensive and intensive margin of multidimensional poverty. The empirical application of the method consists of measuring multidimensional poverty in ten selected countries using four waves of EU‐SILC data (2008–2014). [ABSTRACT FROM AUTHOR]

Objectives: To objectively assess the quality of the published clinical practice guidelines (CPGs) on the management of pregnancies complicated by placenta accreta spectrum (PAS)disorders. Methods: MEDLINE, Embase, Scopus, and ISI Web of Science databases were searched. The following aspects related to the management of pregnancies with suspected PAS disorders were evaluated: risk factors for PAS, prenatal diagnosis, role of interventional radiology and ureteral stenting, and optimal surgical management. The assessment of risk of bias and quality assessment of the CPGs were performed using the (AGREE II) tool (Brouwers et al., 2010). To define a CPG as of good quality we adopted a cut‐off score >60%. Results: Nine CPGs were included. Specific risk factors for referral were assessed by 44.4% (4/9) of CPGs, mainly consisting in the presence of placenta previa and a prior cesarean delivery or uterine surgery. About 55.6% of CPGs (5/9) suggested ultrasound assessment of women with risk factors for PAS in the second and third trimester of pregnancy and 33.3% (3/9) recommended magnetic resonance imaging (MRI); 88.9% (8/9) of CPGs recommended cesarean delivery at 34–37 weeks of gestation. There was not generally consensus on the use of interventional radiology and ureteral stenting before surgery for PAS. Finally, hysterectomy was the recommend surgical approach by 77.8% (7/9) of the included CPGs. Conclusion: Most of the published CPGs on PAS are generally of good quality. There was general agreement among the different CPGs on PAS as a regard as risk stratification, timing at diagnosis and delivery but not on the indication for MRI, use of interventional radiology and ureteral stenting. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of fetal brain magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses with congenital cytomegalovirus (CMV) infection and normal neurosonography. Methods: This was a multicenter, retrospective cohort study of patients examined between 2012 and 2021 in 11 referral fetal medicine centers in Italy. Inclusion criteria were fetuses with congenital CMV infection diagnosed by polymerase chain reaction analysis of amniotic fluid, pregnancies that underwent detailed multiplanar ultrasound assessment of the fetal brain as recommended by the International Society of Ultrasound in Obstetrics and Gynecology, maternal age ≥ 18 years, normal fetal karyotype and MRI performed within 3 weeks after the last ultrasound examination. The primary outcome was the rate of central nervous system (CNS) anomalies detected exclusively on MRI and confirmed after birth or autopsy in fetuses with a prenatal diagnosis of congenital CMV infection and normal neurosonography at diagnosis. Additional CNS anomalies were classified into anomalies of the ventricular and the periventricular zone, intracranial calcifications in the basal ganglia or germinal matrix, destructive encephalopathy in the white matter, malformations of cortical development, midline anomalies, posterior fossa anomalies and complex brain anomalies. We evaluated the relationship between the incidence of structural CNS malformations diagnosed exclusively on fetal MRI and a number of maternal and gestational characteristics. Univariate and multivariate logistic regression analyses were used to identify and adjust for potential independent predictors of the MRI diagnosis of fetal anomalies. Results: The analysis included 95 fetuses with a prenatal diagnosis of congenital CMV infection and normal neurosonography referred for prenatal MRI. The rate of structural anomalies detected exclusively at fetal MRI was 10.5% (10/95). When considering the type of anomaly, malformations of cortical development were detected on MRI in 40.0% (4/10) of fetuses, destructive encephalopathy in 20.0% (2/10), intracranial calcifications in the germinal matrix in 10.0% (1/10) and complex CNS anomalies in 30.0% (3/10). On multivariate logistic regression analysis, only CMV viral load in the amniotic fluid, expressed as a continuous variable (odds ratio (OR), 1.16 (95% CI, 1.02–1.21); P = 0.02) or categorical variable (> 100 000 copies/mL) (OR, 12.0 (95% CI, 1.2–124.7); P = 0.04), was independently associated with the likelihood of detecting fetal anomalies on MRI. Associated anomalies were detected exclusively at birth and missed by both prenatal neurosonography and fetal MRI in 3.8% (3/80) of fetuses with congenital CMV infection. Conclusions: Fetal brain MRI can detect additional anomalies in a significant proportion of fetuses with congenital CMV infection and negative neurosonography. Viral load in the amniotic fluid was an independent predictor of the risk of associated anomalies in these fetuses. The findings of this study support a longitudinal evaluation using fetal MRI in congenital CMV infection, even in cases with negative neurosonography at diagnosis. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Copyright of Functional Ecology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

B Methods: b This open-label, phase 3 trial, with blinded centralized PET assessment, accrued untreated pts aged 18-60 with advanced-stage HL (IIB extranodal and/or bulky, III, IV) at 46 FIL Centers. B Introduction: b PET-adapted ABVD with deferred intensification is the favored therapy for most patients with advanced Hodgkin Lymphoma (HL), while upfront intensification ("first hit") with escBEACOPP remains an option in the high-risk disease. FRONTLINE INTENSIFIED ABVD DEMONSTRATES SUPERIOR EFFICACY THAN PET-ADAPTED ABVD IN ADVANCED HODGKIN LYMPHOMA: THE FIL-ROUGE PHASE 3 TRIAL BY THE FONDAZIONE ITALIANA LINFOMI. [Extracted from the article]

Encore Abstract - previously submitted to AACR 2023 The research was funded by: MorphoSys AG Keyword: Aggressive B-cell non-Hodgkin lymphoma B Conflicts of interests pertinent to the abstract. b B J. Duell b Research funding: MorphoSys AG, Regeneron B P. Abrisqueta b Consultant or advisory role: Janssen, Celgene, AbbVie, AstraZeneca Honoraria: Janssen, Celgene, AbbVie, AstraZeneca, Gilead Other remuneration: Speakers' bureau: Janssen, Celgene, AbbVie, AstraZeneca, Gilead B M. Andre b Research funding: Roche, Johnson & Johnson, Takeda Educational grants: Roche, Bristol-Myers-Squib, Celgene, Gilead, AbbVie, AstraZeneca Other remuneration: Advisory board: Takeda, Bristol-Myers-Squibb, Karyopharm, Gilead, Incyte. B Introduction: b Tafasitamab, an anti-CD19 immunotherapy that enhances antibody-dependent cellular cytotoxicity and phagocytosis, received accelerated approval in the USA and conditional authorization in Europe in combination with lenalidomide (LEN) for patients (pts) with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem cell transplant (ASCT) based on the results of the open-label, multicenter, single-arm, Phase II L-MIND study (NCT02399085; Salles G., et al. [Extracted from the article]

B Introduction: b ZANU (BGB-3111), a potent next-generation Bruton tyrosine kinase inhibitor, is approved in various countries for R/R MZL based on the MAGNOLIA study (NCT03846427) primary analysis. Efficacy was assessed by positron emission tomography (PET)-based Lugano criteria for pts with IRC-confirmed fluorodeoxyglucose (FDG)-avid disease at baseline; non-avid pts were assessed by computed tomography (CT)-based criteria. [Extracted from the article]

Conservation programs have been slow to integrate socio‐economic indicators into decision making despite growing recognition that addressing social‐ecological systems improves outcomes for nature and people. Our goal was to identify small, comprehensive sets of socio‐economic indicators for conservation programs designed to (1) improve agricultural soil health and reduce sediment and nutrient loading to freshwater systems, (2) restore Great Lakes coastal wetlands, and (3) implement green stormwater infrastructure in cities. We piloted a structured decision‐making process to select indicators more objectively and transparently. Important elements of our process were (a) using a human quality‐of‐life framework to identify potential indicators and (b) evaluating indicators' relevance to conservation, resonance with communities, and data‐availability. The programs identified 278 potential indicators across seven quality‐of‐life domains, of which 78 were evaluated against six selection criteria. For each program, we developed intended use scenarios, assigned relative weights to selection criteria, and used these weights to calculate a weighted sum of the indicator's criteria scores and rank indicators. Across programs and intended uses, 21 indicators achieved top‐five rankings; indicators for flood risk and damage were common across all three programs. Our collaborative approach provided opportunities to evaluate indicator selections across quality‐of‐life domain, conservation program, and intended uses. [ABSTRACT FROM AUTHOR]

Objectives: To report the rate of visualization of the pericallosal artery (PCA) in the first trimester of pregnancy (11–14 weeks). Methods: Prospective observational study of consecutive fetuses undergoing first trimester risk assessment for chromosomal anomalies. The presence of PCA was assessed in a midsagittal view of fetal brain using high‐definition power Color Doppler. A normal course of the PCA was defined as the visualization of an artery emerging from the anterior cerebral artery running parallel the corpus callosum (CC). The reference standard was the visualization of CC and PCA between the 20 and 22 weeks of gestation. We also performed a systematic review and meta‐analysis of the published literature. Multivariate logistic regression and random‐effect meta‐analyses of proportion were used to analyze the data. Results: Cohort study: Five‐hundred women were included. PCA was identified trans‐abdominally or transvaginally at 11–14 weeks of gestation in 98.8% (95% CI 97.4–99.6: 494/500); of the four cases of PCA not identified one had a diagnosis of complete agenesis of the corpus callosum during the anomaly scan which was confirmed at birth. Systematic review of the published literature: Six studies (1093 fetuses, including the present series) were included. The PCA was detected at the 11–14 weeks scan and confirmed to co‐exist with a normal CC at time of the anomaly scan in 96.9% (95% CI 93.8–99.0); 20.6% (95% CI 5.7–41.7) of fetuses with no clear identification of the PCA at the 11–14 weeks scan had a normal appearance of the CC at the time of anomaly scan. Conclusion: Prenatal ultrasonography has a high diagnostic accuracy in detecting PCA in the first trimester. Visualization of the PCA at the time of 11–14 scan is highly specific for the presence of a normal CC later in pregnancy. [ABSTRACT FROM AUTHOR]

De novo thymidylate synthesis is a crucial pathway for normal and cancer cells. Deoxythymidine monophosphate (dTMP) is synthesized by the combined action of three enzymes: serine hydroxymethyltransferase (SHMT1), dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS), with the latter two being targets of widely used chemotherapeutics such as antifolates and 5‐fluorouracil. These proteins translocate to the nucleus after SUMOylation and are suggested to assemble in this compartment into the thymidylate synthesis complex. We report the intracellular dynamics of the complex in cancer cells by an in situ proximity ligation assay, showing that it is also detected in the cytoplasm. This result indicates that the role of the thymidylate synthesis complex assembly may go beyond dTMP synthesis. We have successfully assembled the dTMP synthesis complex in vitro, employing tetrameric SHMT1 and a bifunctional chimeric enzyme comprising human thymidylate synthase and dihydrofolate reductase. We show that the SHMT1 tetrameric state is required for efficient complex assembly, indicating that this aggregation state is evolutionarily selected in eukaryotes to optimize protein–protein interactions. Lastly, our results regarding the activity of the complete thymidylate cycle in vitro may provide a useful tool with respect to developing drugs targeting the entire complex instead of the individual components. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the methodology of studies reporting reference ranges for fetal brain structures on magnetic resonance imaging (MRI). Methods: MEDLINE, EMBASE, CINAHL and the Web of Science databases were searched electronically up to 31 December 2020 to identify studies investigating biometry and growth of the fetal brain and reporting reference ranges for brain structures using MRI. The primary aim was to evaluate the methodology of these studies. A list of 26 quality criteria divided into three domains, including 'study design', 'statistical and reporting methods' and 'specific aspects relevant to MRI', was developed and applied to evaluate the methodological appropriateness of each of the included studies. The overall quality score of a study, ranging between 0 and 26, was defined as the sum of scores awarded for each quality criterion and expressed as a percentage (the lower the percentage, the higher the risk of bias). Results: Fifteen studies were included in this systematic review. The overall mean quality score of the studies evaluated was 48.7%. When focusing on each domain, the mean quality score was 42.0% for 'study design', 59.4% for 'statistical and reporting methods' and 33.3% for 'specific aspects relevant to MRI'. For the 'study design' domain, sample size calculation and consecutive enrolment of women were the items found to be at the highest risk of bias. For the 'statistical and reporting methods' domain, the presence of regression equations for mean and SD for each measurement, the number of measurements taken for each variable and the presence of postnatal assessment information were the items found to be at the highest risk of bias. For the 'specific aspects relevant to MRI' domain, whole fetal brain assessment was not performed in any of the included studies and was therefore considered to be the item at the highest risk of bias. Conclusions: Most of the previously published studies reporting fetal brain reference ranges on MRI are highly heterogeneous and have low‐to‐moderate quality in terms of methodology, which is similar to the findings reported for ultrasound studies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the efficacy and safety of pomalidomide, bortezomib, and dexamethasone (PVd) vs bortezomib and dexamethasone (Vd) by age, renal function, and high‐risk cytogenetic abnormalities in lenalidomide‐pretreated patients with multiple myeloma at first relapse. Methods: OPTIMISMM was a phase 3, multicenter, open‐label, randomized study (NCT01734928; N = 559). The primary endpoint was progression‐free survival (PFS). Results: Overall, 226 patients had received one prior line of therapy. PVd significantly prolonged PFS vs Vd in patients aged ≤65 years (median, 22.0 vs 13.1 months; P =.0258) and >65 years (median, 17.6 vs 9.9 months; P =.0369). Median PFS in patients with renal impairment (RI; creatinine clearance <60 mL/min) was 15.1 months with PVd vs 9.5 months with Vd (hazard ratio [HR], 0.67 [95% CI, 0.34‐1.34]). In patients without RI, median PFS was 22.0 vs 13.1 months (HR, 0.45 [95% CI, 0.27‐0.76]). In patients with high‐risk cytogenetics, median PFS was 14.7 vs 9.9 months (HR, 0.39 [95% CI, 0.13‐1.17]). PVd significantly improved overall response rate vs Vd in all subgroups. The safety profile of PVd was consistent with previous reports. Conclusions: These findings confirmed the benefits of PVd at first relapse, including in patients with poor prognostic factors. [ABSTRACT FROM AUTHOR]

Net ecosystem CO2 exchange is the result of net carbon uptake by plant photosynthesis and carbon loss by soil and plant respiration. Temperature increases due to climate change can modify the equilibrium between these fluxes and trigger ecosystem‐climate feedbacks that can accelerate climate warming. As these dynamics have not been well studied in dry shrublands, we subjected a Mediterranean shrubland to a 10‐year night‐time temperature manipulation experiment that analyzed ecosystem carbon fluxes associated with dominant shrub species, together with several plant parameters related to leaf photosynthesis, leaf morphology, and canopy structure. Under moderate night‐time warming (+0.9°C minimum daily temperature, no significant reduction in soil moisture), Cistus monspeliensis formed shoots with more leaves that were relatively larger and denser canopies that supported higher plant‐level photosynthesis rates. Given that ecosystem respiration was not affected, this change in canopy morphology led to a significant enhancement in net ecosystem exchange (+47% at midday). The observed changes in shoot and canopy morphology were attributed to the improved nutritional state of the warmed plants, primarily due to changes in nitrogen cycling and higher nitrogen resorption efficiency in senescent leaves. Our results show that modifications in plant morphology triggered by moderate warming affected ecosystem CO2 fluxes, providing the first evidence for enhanced daytime carbon uptake in a dry shrubland ecosystem under experimental warming. [ABSTRACT FROM AUTHOR]

Following the debate on the relationship between business and financial cycle rekindled in the last decade since the global financial crisis, we assess the ability of some financial indicators to track the Italian business cycle. We mostly use credit variables to detect the turning points and to estimate the probability of recession in real time. A dynamic factor model with Markov‐switching regimes is used to handle a large data set and to cope with the nonlinear evolution of the business cycle. The in‐sample results strongly support the capacity of credit variables to estimate the probability of recessions and the implied coincident indicator proves their ability to fit the business cycle. Also in real time the contribution of credit is not negligible compared to that of the industrial production, currently used for the conjunctural analysis. [ABSTRACT FROM AUTHOR]

Background: Sub‐optimal classification, interpretation and response to intrapartum electronic fetal monitoring using cardiotocography are known problems. Training is often recommended as a solution, but there is lack of clarity about the effects of training and which type of training works best. Objectives: Systematic review of the effects of training healthcare professionals in intrapartum cardiotocography (PROSPERO protocol: CRD42017064525). Search strategy: CENTRAL, Cochrane Library, MEDLINE, EMBASE, PsycINFO, British Nursing Database, CINAHL, ERIC, Scopus, Web of Science, ProQuest, grey literature and ongoing clinical trials were searched. Selection criteria: Primary studies that reported impact of training healthcare professionals in intrapartum cardiotocography. Title/abstract, full‐text screening and quality assessment were conducted in duplicate. Data collection and analysis: Data were synthesised both narratively and using meta‐analysis. Risk of bias and overall quality were assessed with the Mixed Methods Appraisal Tool and GRADE. Main results: Sixty‐four studies were included. Overall, training and reporting were heterogeneous, the outcomes evaluated varied widely and study quality was low. Five randomised controlled trials reported that training improved knowledge of maternity professionals compared with no training, but evidence was of low quality. Evidence for the impact of cardiotocography training on neonatal and maternal outcomes was limited, showed inconsistent effects, and was of low overall quality. Evidence for the optimal content and method of delivery of training was very limited. Conclusions: Given the scale of harm and litigation claims associated with electronic fetal monitoring, the evidence‐base for training requires improvement. It should address intervention design, evaluation of clinical outcomes and system‐wide contexts of sub‐optimal practice. Training in fetal monitoring: systematic review finds little evidence of impact on neonatal outcomes. Training in fetal monitoring: systematic review finds little evidence of impact on neonatal outcomes. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the risk factors, histopathological correlations and diagnostic accuracy of prenatal imaging in pregnancies complicated by posterior placenta accreta spectrum (PAS) disorders.Methods: MEDLINE, EMBASE and CINAHL were searched for studies reporting on women with posterior PAS. Inclusion criteria were women with posterior PAS confirmed either at surgery or on histopathological analysis. The outcomes explored were risk factors for posterior PAS, histopathological correlation and the diagnostic accuracy of ultrasound and magnetic resonance imaging (MRI) in detecting posterior PAS. Random-effects meta-analysis of proportions was used to analyze the data.Results: Twenty studies were included. Placenta previa was present in 92.8% (107/114; 17 studies) of pregnancies complicated by posterior PAS, while 76.1% (53/88; 11 studies) of women had had prior uterine surgery, mainly a Cesarean section (CS) or curettage and 82.5% (66/77; 10 studies) were multiparous. When considering histopathological analysis in women affected by posterior PAS, 77.5% (34/44; 11 studies) had placenta accreta, 19.5% (8/44; 11 studies) had placenta increta and 9.3% (2/44; 11 studies) had placenta percreta. Of the cases of posterior PAS disorder, 52.4% (31/63; 12 studies) were detected prenatally on ultrasound, while 46.7% (32/63; 12 studies) were diagnosed only at birth. When exploring the distribution of the classic ultrasound signs of PAS, placental lacunae were present in 39.0% (12/30; seven studies), loss of the clear zone in 41.1% (13/30; seven studies) and bladder-wall interruption in 16.6% (4/30; seven studies) of women, while none of the included cases showed hypervascularization at the bladder-wall interface. When assessing the role of MRI in detecting posterior PAS, 73.5% (26/32; 11 studies) of cases were detected on prenatal MRI, while 26.5% (6/32; 11 studies) were discovered only at the time of CS.Conclusions: Placenta previa, prior uterine surgery and multiparity represent the most commonly reported risk factors for posterior PAS. Ultrasound had a very low diagnostic accuracy in detecting these disorders prenatally. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [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]

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoonotic coronavirus that crossed species to infect humans, causing coronavirus disease 2019 (COVID-19). Despite a potentially higher risk of pregnant women acquiring SARS-CoV-2 infection compared with the non-pregnant population (particularly in some ethnic minorities), no additional specific recommendations to avoid exposure are needed in pregnancy. The most common clinical symptoms and laboratory signs of SARS-CoV-2 infection in pregnancy are fever, cough, lymphopenia and elevated C-reactive protein levels. Pregnancy is associated with a higher risk of severe SARS-CoV-2 infection compared with the non-pregnant population, including pneumonia, admission to the intensive care unit and death, even after adjusting for potential risk factors for severe outcomes. The risk of miscarriage does not appear to be increased in women with SARS-CoV-2 infection. Evidence with regards to preterm birth and perinatal mortality is conflicting, but these risks are generally higher only in symptomatic, hospitalized women. The risk of vertical transmission, defined as the transmission of SARS-CoV-2 from the mother to the fetus or the newborn, is generally low. Fetal invasive procedures are considered to be generally safe in pregnant women with SARS-CoV-2 infection, although the evidence is still limited. In pregnant women with COVID-19, use of steroids should not be avoided if clinically indicated; the preferred regimen is a 2-day course of dexamethasone followed by an 8-day course of methylprednisolone. Non-steroidal anti-inflammatory drugs may be used if there are no contraindications. Hospitalized pregnant women with severe COVID-19 should undergo thromboprophylaxis throughout the duration of hospitalization and at least until discharge, preferably with low molecular weight heparin. Hospitalized women who have recovered from a period of serious or critical illness with COVID-19 should be offered a fetal growth scan about 14 days after recovery from their illness. In asymptomatic or mildly symptomatic women who have tested positive for SARS-CoV-2 infection at full term (i.e. ≥ 39 weeks of gestation), induction of labor might be reasonable. To date, there is no clear consensus on the optimal timing of delivery for critically ill women. In women with no or few symptoms, management of labor should follow routine evidence-based guidelines. Regardless of COVID-19 status, mothers and their infants should remain together and breastfeeding, skin-to-skin contact, kangaroo mother care and rooming-in throughout the day and night should be practiced, while applying necessary infection prevention and control measures. Many pregnant women have already undergone vaccination, mostly in the USA where the first reports show no significant difference in pregnancy outcomes in pregnant women receiving SARS-CoV-2 vaccination during pregnancy compared with the background risk. Vaccine-generated antibodies were present in the umbilical cord blood and breast milk samples of pregnant and lactating women who received the mRNA COVID-19 vaccine. Based on the available limited data on the safety of the COVID-19 vaccine in pregnancy, it seems reasonable to offer the option of vaccination to pregnant women after accurate counseling on the potential risk of a severe course of the disease and the unknown risk of fetal exposure to the vaccine. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To elucidate whether pre-eclampsia (PE) and the gestational age at onset of the disease (early- vs late-onset PE) have an impact on the risk of long-term maternal cardiovascular complications.Methods: MEDLINE, EMBASE and Scopus databases were searched until 15 April 2020 for studies evaluating the incidence of cardiovascular events in women with a history of PE, utilizing combinations of the relevant MeSH terms, keywords and word variants for 'pre-eclampsia', 'cardiovascular disease' and 'outcome'. Inclusion criteria were cohort or case-control design, inclusion of women with a diagnosis of PE at the time of the first pregnancy, and sufficient data to compare each outcome in women with a history of PE vs women with previous normal pregnancy and/or in women with a history of early- vs late-onset PE. The primary outcome was a composite score of maternal cardiovascular morbidity and mortality, including cardiovascular death, major cardiovascular and cerebrovascular events, hypertension, need for antihypertensive therapy, Type-2 diabetes mellitus, dyslipidemia and metabolic syndrome. Secondary outcomes were the individual components of the primary outcome analyzed separately. Data were combined using a random-effects generic inverse variance approach. MOOSE guidelines and the PRISMA statement were followed.Results: Seventy-three studies were included. Women with a history of PE, compared to those with previous normotensive pregnancy, had a higher risk of composite adverse cardiovascular outcome (odds ratio (OR), 2.05 (95% CI, 1.9-2.3)), cardiovascular death (OR, 2.18 (95% CI, 1.8-2.7)), major cardiovascular events (OR, 1.80 (95% CI, 1.6-2.0)), hypertension (OR, 3.93 (95% CI, 3.1-5.0)), need for antihypertensive medication (OR, 4.44 (95% CI, 2.4-8.2)), dyslipidemia (OR, 1.32 (95% CI, 1.3-1.4)), Type-2 diabetes (OR, 2.14 (95% CI, 1.5-3.0)), abnormal renal function (OR, 3.37 (95% CI, 2.3-5.0)) and metabolic syndrome (OR, 4.30 (95% CI, 2.6-7.1)). Importantly, the strength of the associations persisted when considering the interval (< 1, 1-10 or > 10 years) from PE to the occurrence of these outcomes. When stratifying the analysis according to gestational age at onset of PE, women with previous early-onset PE, compared to those with previous late-onset PE, were at higher risk of composite adverse cardiovascular outcome (OR, 1.75 (95% CI, 1.0-3.0)), major cardiovascular events (OR, 5.63 (95% CI, 1.5-21.4)), hypertension (OR, 1.48 (95% CI, 1.3-1.7)), dyslipidemia (OR, 1.51 (95% CI, 1.3-1.8)), abnormal renal function (OR, 1.52 (95% CI, 1.1-2.2)) and metabolic syndrome (OR, 1.66 (95% CI, 1.1-2.5).Conclusions: Both early- and late-onset PE represent risk factors for maternal adverse cardiovascular events later in life. Early-onset PE is associated with a higher burden of cardiovascular morbidity and mortality compared to late-onset PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Summary: Treatment for follicular lymphoma (FL) in the elderly is not well standardized. A phase II, multicentre, single arm trial was conducted in this setting with a brief chemoimmunotherapy regimen. Treatment consisted in four monthly courses of rituximab, bendamustine and mitoxantrone (R‐BM) followed by 4 weekly rituximab as consolidation; rituximab maintenance was not applied because the drug was not licensed at the time of enrolment. The primary endpoint was the complete remission rate (CR). Seventy‐six treatment‐naive FL patients (aged 65–80 and a "FIT" score, according to the Comprehensive Geriatric Assessment) were enrolled. CR was documented in 59/76 patients (78%), partial remission in 12 (16%) and stable/progressive disease in five (6%) with an overall response rate in 71/76 (94%). Median follow‐up was 44 months with 3‐year progression‐free‐survival (PFS) and overall‐survival of 67% and 92% respectively. Nine deaths occurred, three of progressive disease. The regimen was well tolerated and the most frequent severe toxicity was neutropenia (18% of the cycles). Bcl‐2/IGH rearrangement was found in 40/75 (53%) of evaluated patients. R‐BM was highly effective in clearing polymerase chain reaction‐detectable disease: 29/31 (96%) evaluated patients converted to bcl‐2/IGH negativity at the end of treatment. A brief R‐BM regimen plus rituximab consolidation is effective and safe in "FIT" elderly, treatment‐naïve, FL patients, inducing high CR and molecular remission rates with prolonged PFS. [ABSTRACT FROM AUTHOR]

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]

The main aim of this systematic review was to explore the outcome of fetuses with isolated echogenic bowel (EB) on antenatal ultrasound. Inclusion criteria were singleton pregnancies with isolated EB no associated major structural anomalies at the time of diagnosis. The outcomes observed were: chromosomal anomalies, cystic fibrosis (CF), associated structural anomalies detected only at follow‐up scans and at birth, regression during pregnancy, congenital infections, intra‐uterine (IUD), neonatal (NND) and perinatal (PND) death. Twenty‐five studies (12 971 fetuses) were included. Chromosomal anomalies occurred in 3.3% of the fetuses, mainly Trisomy 21 and aneuploidies involving the sex chromosomes. Cystic fibrosis occurred in 2.2%. Congenital infections affected 2.2%, mainly congenital Cytomegalovirus (CMV) infection. The majority of fetuses with EB experienced regression or disappearance of the EB at follow‐up scans. Associated anomalies were detected at a follow‐up scan in 1.8%. Associated anomalies were detected at birth and missed at ultrasound in 2.1% of cases. IUD occurred in 3.2% of cases while the corresponding figures for NND and PND were 0.4% and 3.1%. Fetuses with EB are at increased risk of adverse perinatal outcome, highlighting the need for a thorough antenatal management and postnatal follow‐up. Assessment during pregnancy and after birth should be performed in order to look for signs of fetal aneuploidy, congenital infections and associated structural anomalies. [ABSTRACT FROM AUTHOR]

Introduction: Corpus callosum agenesis (ACC) is frequently diagnosed during fetal life; its prognosis depends also on additional anomalies. The additional value of fetal magnetic resonance imaging (MRI) in fetuses with "isolated" complete (cACC) and partial (pACC) agenesis of the corpus callosum on ultrasound is still debated. Material and methods: We performed a systematic literature review and meta‐analysis including fetuses with a prenatal diagnosis of cACC and pACC without associated structural anomalies on ultrasound, undergoing fetal MRI. The primary outcome was the rate of additional anomalies detected at fetal MRI. Further analyses assessed the effect of type of ultrasound assessment (neurosonography vs standard axial assessment), gestational age at fetal MRI and rate of postnatally detected brain anomalies. Random‐effect meta‐analyses of proportions were used to analyze the data. Results: Fourteen studies (798 fetuses) were included. In cases with isolated cACC, 10.9% (95% CI 4.1‐20.6) and 4.3% (95% CI 1.4‐8.8) additional anomalies were detected by fetal MRI and postnatally, respectively. Stratifying according to the type of ultrasound assessment, the rate of associated anomalies detected only on fetal MRI was 5.7% (95% CI 0.5‐16.0) with dedicated neurosonography and 18.5% (95% CI 7.8‐32.4) with a standard axial assessment. In fetuses with isolated pACC, 13.4% (95% CI 4.0‐27.0) and 16.2% (95% CI 5.9‐30.3) additional anomalies were detected by fetal MRI or postnatally, respectively. Stratifying according to the type of ultrasound assessment, the rate of associated anomalies detected only on fetal MRI was 11.4% (95% CI 2.7‐25.0) when dedicated neurosonography was performed. Cortical and posterior fossa anomalies represented the most common anomalies missed at ultrasound with both cACC and pACC. Due to the very small number of included cases, stratification according to early (<24 weeks of gestation) and late (>24 weeks) fetal MRI could not be done for either cACC or pACC. Conclusions: The rate of associated anomalies detected exclusively at fetal MRI in isolated ACC undergoing neurosonography is lower than previously reported. Cortical and posterior fossa anomalies are among the most common anomalies detected exclusively at MRI, thus confirming the crucial role of fetal MRI in determining the prognosis of these fetuses. However, some anomalies still go undetected prenatally and this should be stressed during parental counseling. [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]

Background: Atopic dermatitis (AD) is a chronic inflammatory disease. Recently, dupilumab was approved for moderate‐to‐severe AD. D‐OCT is a noninvasive tool for the characterization of skin diseases. Objective: To describe the changes observed with D‐OCT in lesional and clinically healthy skin of patients with refractory severe AD under dupilumab treatment. Methods: We analyzed AD lesions and healthy skin by D‐OCT. Clinical scores of AD severity were assessed at baseline (T0) and after 1 and 3 months of treatment (T1, T2). Descriptive statistics, chi‐square test, and t test were used to compare the analyzed parameters over time and between AD lesions and clinically healthy skin. Results: At baseline, average EASI was 45.7. During the follow‐up, EASI75 and EASI90 were achieved in 57% and 36% of patients at T1 and 100% and 86% of patients at T2, respectively. Lesional skin D‐OCT parameters related to epidermal remodeling and inflammation evidenced a significant improvement after 1 month of treatment. In clinically healthy skin, D‐OCT parameters improved significantly after 3 months of treatment, especially for collagen remodeling and inflammation. Conclusion: The study demonstrates that the clinical improvement of severe AD patients under dupilumab treatment is correlated with specific D‐OCT changes of patients' lesional and clinically healthy skin. [ABSTRACT FROM AUTHOR]

Deicing agents cause soil salinization and degradation in urban areas. We assessed the capacity of urban lawns to maintain carbon sequestration and nutrient cycling with increasing soil salinity. The sensitivity to soil salinity of the main ecosystem players: plants and microorganisms were assessed considering their complex interactions between each other and environment. The effects of low and moderate soil salinization by common deicing agent (NaCl) were evaluated in mesocosms planted with two urban lawns: Lolium perenne and mixture of grasses. Mesocosm‐, plant‐, and soil‐level gas exchange were assessed on a short‐term (days) and long‐term (months) scales. Microbial response was characterized by analyzing the microbial properties and activities of nine enzymes. Carbon balance remained independent on the salinity due to cancelling effect of lowered gross primary production (GPP, −20%), decreased C input by plants into the soil (−40% for mixture) balanced by slower microbial decomposition of organic matter (−20%) and so, lower soil respiration (−35%). GPP declined as a long‐term response by a combination of stomatal constraint on photosynthesis with leaf respiration increase. Toxic effects of salinization on soil respiration were observed only for temperatures above 15°C. Microbial community with high C:N ratio (common for fungi) was the most sensitive to salinization. The death of microbial biomass (−31% for Lolium) and cell lysis increased soil enzyme activities (+38% for Lolium). We conclude that C balance of urban lawns remain homeostatic at secondary salinization. Temperature effects and plant‐microbial interactions will determine C and nutrients cycling under salinity stress in urban lawns. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate subsequent reproductive among women with a prior cesarean scar pregnancy (CSP). Material and methods: MEDLINE, Embase and ClinicalTrials.gov databases were searched. Inclusion criteria were women with a prior CSP, defined as the gestational sac or trophoblast within the dehiscence/niche of the previous cesarean section scar or implanted on top of it. The primary outcome was the recurrence of CSP; secondary outcomes were the chance of achieving a pregnancy after CSP, miscarriage, preterm birth, uterine rupture and the occurrence of placenta accreta spectrum disorders. Subgroup analysis according to the management of CSP (surgical vs non‐surgical) was also performed. Random effect meta‐analyses of proportions were used to analyze the data. Results: Forty‐four studies (3598 women with CSP) were included. CSP recurred in 17.6% of women. Miscarriage, preterm birth and placenta accreta spectrum disorders complicated 19.1% (65/341), 10.3% (25/243) and 4.0% of pregnancies, and 67.0% were uncomplicated. When stratifying the analysis according to the type of management, CSP recurred in 21% of women undergoing surgical and in 15.2% of those undergoing non‐surgical management. Placenta accreta spectrum disorders complicated 4.0% and 12.0% of cases, respectively. Conclusions: Women with a prior CSP are at high risk of recurrence, miscarriage, preterm birth and placenta accreta spectrum. There is still insufficient evidence to elucidate whether the type of management adopted (surgical vs non‐surgical) can impact reproductive outcome after CSP. Further large, prospective studies sharing an objective protocol of prenatal management and long‐term follow up are needed to establish the optimal management of CSP and to elucidate whether it may affect its risk of recurrence and pregnancy outcome in subsequent gestations. [ABSTRACT FROM AUTHOR]

Summary: Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor approved for the treatment of myelofibrosis (MF). Ruxolitinib was assessed in JUMP, a large (N = 2233), phase 3b, expanded‐access study in MF in countries without access to ruxolitinib outside a clinical trial, which included patients with low platelet counts (<100 × 109/l) and patients without splenomegaly – populations that have not been extensively studied. The most common adverse events (AEs) were anaemia and thrombocytopenia, but they rarely led to discontinuation (overall, 5·4%; low‐platelet cohort, 12·3%). As expected, rates of worsening thrombocytopenia were higher in the low‐platelet cohort (all grades, 73·2% vs. 53·5% overall); rates of anaemia were similar (all grades, 52·9% vs. 59·5%). Non‐haematologic AEs, including infections, were mainly grade 1/2. Overall, ruxolitinib led to meaningful reductions in spleen length and symptoms, including in patients with low platelet counts, and symptom improvements in patients without splenomegaly. In this trial, the largest study of ruxolitinib in patients with MF to date, the safety profile was consistent with previous reports, with no new safety concerns identified. This study confirms findings from the COMFORT studies and supports the use of ruxolitinib in patients with platelet counts of 50–100 × 109/l. (ClinicalTrials.gov identifier NCT01493414). [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]

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. [ABSTRACT FROM AUTHOR]

Objective: To report the perinatal outcome of singleton pregnancies complicated by placental chorioangioma diagnosed on prenatal ultrasound.Methods: MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov databases were searched for studies reporting the outcome of pregnancies complicated by placental chorioangioma. Inclusion criteria were singleton pregnancy diagnosed with placental chorioangioma on prenatal ultrasound, with no other associated structural anomaly. The primary outcome was perinatal mortality. Secondary outcomes included associated non-structural anomalies detected on prenatal ultrasound (including fetal hydrops, anemia, polyhydramnios, signs of hyperdynamic circulation and small-for-gestational-age (SGA) fetus), SGA at birth, composite neonatal morbidity and preterm birth. Outcome was assessed separately in pregnancies undergoing and those not undergoing fetal therapy. Subanalyses were performed according to the presence of hydrops and the size of the tumor in all pregnancies diagnosed with chorioangioma. Random-effects meta-analyses of proportions were used to analyze the data.Results: Twenty-eight studies (161 pregnancies) were included. In pregnancies complicated by chorioangioma that did not undergo intervention, intrauterine death occurred in 8.2% (95% CI, 3.8-15.0%), while neonatal death and perinatal death occurred in 3.8% (95% CI, 1.0-8.1%) and 11.1% (95% CI, 5.0-19.4%), respectively. SGA at birth was present in 24.0% (95% CI, 13.5-36.5%) of cases, while preterm birth < 37 weeks complicated 34.1% (95% CI, 21.1-48.3%) of pregnancies. Composite neonatal morbidity occurred in 12.0% (95% CI, 4.5-22.3%) of cases. On ultrasound, signs of fetal hyperdynamic circulation were present in 21.0% (95% CI, 9.6-35.3%) of cases, while peak systolic velocity in the fetal middle cerebral artery was increased in 20.6% (95% CI, 10.9-32.3%). Subanalysis according to the size of chorioangioma, including both pregnancies that did and those that did not undergo intervention, showed a progressive increase in the occurrence of most of the outcomes explored with increasing size of the tumor. Furthermore, the prevalence of adverse perinatal outcome was high in pregnancies complicated by chorioangioma presenting with fetal hydrops. There was no randomized controlled trial comparing intervention vs expectant management in pregnancies complicated by chorioangioma with signs of fetal compromise (hydrops or hyperdynamic circulation). Overall, perinatal mortality occurred in 31.2% (95% CI, 18.1-46.1%) of fetuses undergoing in-utero therapy, and 57.3% (95% CI, 39.2-74.4%) had resolution of hydrops or hyperdynamic circulation after treatment.Conclusions: Placental chorioangioma is associated with adverse perinatal outcome. The size of the mass and presence of fetal hydrops are likely to be the main determinants of perinatal outcome in affected pregnancies. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To explore the outcome of monochorionic monoamniotic (MCMA) twin pregnancies affected by twin-to-twin transfusion syndrome (TTTS).Methods: MEDLINE and EMBASE databases were searched for studies reporting the outcome of MCMA twin pregnancies complicated by TTTS. The primary outcome was intrauterine death (IUD); secondary outcomes were miscarriage, single IUD, double IUD, neonatal death (NND), perinatal death (PND), survival of at least one twin, survival of both twins and preterm birth (PTB) before 32 weeks' gestation. Outcomes were assessed in MCMA twins affected by TTTS not undergoing intervention and in those treated with amniodrainage, laser therapy or cord occlusion. Subgroup analysis was performed including cases diagnosed before 24 weeks. Random-effects meta-analysis of proportions was used to analyze the data.Results: Fifteen cohort studies, including 888 MCMA twin pregnancies, of which 44 were affected by TTTS, were included in the review. There was no randomized trial comparing the different management options in MCMA twin pregnancies complicated by TTTS. In cases not undergoing intervention, miscarriage occurred in 11.0% of fetuses, while the incidence of IUD, NND and PND was 25.2%, 12.2% and 31.2%, respectively. PTB complicated 50.5% of these pregnancies. In cases treated by laser surgery, the incidence of miscarriage, IUD, NND and PND was 19.6%, 27.4%, 7.4% and 35.9%, respectively, and the incidence of PTB before 32 weeks' gestation was 64.9%. In cases treated with amniodrainage, the incidence of IUD, NND and PND was 31.3%, 13.5% and 45.7% respectively, and PTB complicated 76.2% of these pregnancies. Analysis of cases undergoing cord occlusion was affected by the very small number of included cases. Miscarriage occurred in 19.2%, while there was no case of IUD or NND of the surviving twin. PTB before 32 weeks occurred in 50.0% of these cases.Conclusions: MCMA twin pregnancies complicated by TTTS are at high risk of perinatal mortality and PTB. Further studies are needed in order to elucidate the optimal type of prenatal treatment in these pregnancies. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To perform a systematic review of studies reporting the outcome of fetuses with a prenatal diagnosis of isolated duplex collecting system (DCS).Methods: Inclusion criteria were studies reporting the outcome of fetuses with a prenatal diagnosis of isolated DCS, defined as DCS not associated with other major structural anomalies at the time of diagnosis. The outcomes observed were: imaging features of DCS on prenatal ultrasound, associated anomalies detected exclusively at prenatal follow-up ultrasound and at birth, abnormal karyotype, symptoms at birth (including vesicoureteral reflux [VUR] and urinary tract infections [UTI]), need for and type of surgical approach, complications after surgery, and accuracy of prenatal ultrasound in correctly identifying this anomaly.Results: Eleven studies (284 fetuses with a prenatal diagnosis of DCS) were included. On ultrasound, DCS was associated with ureterocele in 70.7% and with megaureter in 36.6% of cases. Worsening of pelvic/ureteric dilatation was reported to occur in 41.3% of fetuses. At birth, 4.3% of fetuses affected by DCS showed associated renal anomalies. After birth, VUR and UTI presented in 51.3% and 21.7% of children respectively, while 33.6% required surgery. Prenatal diagnosis of DCS was confirmed in 90.9% of included cases.Conclusion: DCS diagnosed prenatally is associated with a generally good outcome. Prenatal ultrasound has a good diagnostic accuracy, while detailed postnatal assessment is required in order to identify associated renal anomalies. [ABSTRACT FROM AUTHOR]