Comparison of different methods of first-trimester screening for preterm pre-eclampsia: cohort study.

OBJECTIVE: To compare the predictive performance of three different mathematical models for first-trimester screening of pre-eclampsia (PE), which combine maternal risk factors with mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF), and two risk-scoring systems. METHODS: This was a prospective cohort study performed in eight fetal medicine units in five different regions of Spain between September 2017 and December 2019. All pregnant women with singleton pregnancy and a non-malformed live fetus attending their routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation were invited to participate in the study. Maternal characteristics and medical history were recorded and measurements of MAP, UtA-PI, serum PlGF and pregnancy-associated plasma protein-A (PAPP-A) were converted into multiples of the median (MoM). Risks for term PE, preterm PE (< 37 weeks' gestation) and early PE (< 34 weeks' gestation) were calculated according to the FMF competing-risks model, the Crovetto et al. logistic regression model and the Serra et al. Gaussian model. PE classification was also performed based on the recommendations of the National Institute for Health and Care Excellence (NICE) and the American College of Obstetricians and Gynecologists (ACOG). We estimated detection rates (DR) with their 95% CIs at a fixed 10% screen-positive rate (SPR), as well as the area under the receiver-operating-characteristics curve (AUC) for preterm PE, early PE and all PE for the three mathematical models. For the scoring systems, we calculated DR and SPR. Risk calibration was also assessed. RESULTS: The study population comprised 10 110 singleton pregnancies, including 32 (0.3%) that developed early PE, 72 (0.7%) that developed preterm PE and 230 (2.3%) with any PE. At a fixed 10% SPR, the FMF, Crovetto et al. and Serra et al. models detected 82.7% (95% CI, 69.6-95.8%), 73.8% (95% CI, 58.7-88.9%) and 79.8% (95% CI, 66.1-93.5%) of early PE; 72.7% (95% CI, 62.9-82.6%), 69.2% (95% CI, 58.8-79.6%) and 74.1% (95% CI, 64.2-83.9%) of preterm PE; and 55.1% (95% CI, 48.8-61.4%), 47.1% (95% CI, 40.6-53.5%) and 53.9% (95% CI, 47.4-60.4%) of all PE, respectively. The best correlation between predicted and observed cases was achieved by the FMF model, with an AUC of 0.911 (95% CI, 0.879-0.943), a slope of 0.983 (95% CI, 0.846-1.120) and an intercept of 0.154 (95% CI, -0.091 to 0.397). The NICE criteria identified 46.7% (95% CI, 35.3-58.0%) of preterm PE at 11% SPR and ACOG criteria identified 65.9% (95% CI, 55.4-76.4%) of preterm PE at 33.8% SPR. CONCLUSIONS: The best performance of screening for preterm PE is achieved by mathematical models that combine maternal factors with MAP, UtA-PI and PlGF, as compared to risk-scoring systems such as those of NICE and ACOG. While all three algorithms show similar results in terms of overall prediction, the FMF model showed the best performance at an individual level. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Performance of first-trimester combined screening for preterm pre-eclampsia: findings from cohort of 10 110 pregnancies in Spain.

OBJECTIVE: To evaluate the diagnostic accuracy of the Fetal Medicine Foundation (FMF) competing-risks model, incorporating maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and placental growth factor (PlGF) (the 'triple test'), for the prediction at 11-13 weeks' gestation of preterm pre-eclampsia (PE) in a Spanish population. METHODS: This was a prospective cohort study performed in eight fetal medicine units in five different regions of Spain between September 2017 and December 2019. All pregnant women with a singleton pregnancy and a non-malformed live fetus attending a routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation were invited to participate. Maternal demographic characteristics and medical history were recorded and MAP, UtA-PI, serum PlGF and pregnancy-associated plasma protein-A (PAPP-A) were measured following standardized protocols. Treatment with aspirin during pregnancy was also recorded. Raw values of biomarkers were converted into multiples of the median (MoM), and audits were performed periodically to provide regular feedback to operators and laboratories. Patient-specific risks for term and preterm PE were calculated according to the FMF competing-risks model, blinded to pregnancy outcome. The performance of screening for PE, taking into account aspirin use, was assessed by calculating the area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% fixed screen-positive rate (SPR). Risk calibration of the model was assessed. RESULTS: The study population comprised 10 110 singleton pregnancies, including 72 (0.7%) that developed preterm PE. In the preterm PE group, compared to those without PE, median MAP MoM and UtA-PI MoM were significantly higher, and median serum PlGF MoM and PAPP-A MoM were significantly lower. In women with PE, the deviation from normal in all biomarkers was inversely related to gestational age at delivery. Screening for preterm PE by a combination of maternal characteristics and medical history with MAP, UtA-PI and PlGF had a DR, at 10% SPR, of 72.7% (95% CI, 62.9-82.6%). An alternative strategy of replacing PlGF with PAPP-A in the triple test was associated with poorer screening performance for preterm PE, giving a DR of 66.5% (95% CI, 55.8-77.2%). The calibration plot showed good agreement between predicted risk and observed incidence of preterm PE, with a slope of 0.983 (95% CI, 0.846-1.120) and an intercept of 0.154 (95% CI, -0.091 to 0.397). CONCLUSIONS: The FMF model is effective in predicting preterm PE in the Spanish population at 11-13 weeks' gestation. This method of screening is feasible to implement in routine clinical practice, but it should be accompanied by a robust audit and monitoring system, in order to maintain high-quality screening. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Clinical phenotypes for risk stratification in small-for-gestational-age fetuses.

OBJECTIVE: To evaluate whether clinical phenotypes of small-for-gestational-age (SGA) fetuses can be identified and used for adverse perinatal outcome risk stratification to facilitate clinical decision-making. METHODS: This was a multicenter observational cohort study conducted in two tertiary care university hospitals. SGA fetuses were classified according to maternal, fetal and placental conditions using a two-step cluster algorithm, in which fetuses with more than one condition were assigned to the cluster associated with the highest mortality risk. Delivery and perinatal outcomes were compared using chi-square test among SGA clusters, and the associations between outcomes and each cluster were evaluated by calculating odds ratios (OR), adjusted for gestational age. RESULTS: The study included 17 631 consecutive singleton pregnancies, of which 1274 (7.2%) were defined as SGA at birth according to INTERGROWTH-21st standards. Nine SGA clinical phenotypes were identified using a predefined conceptual framework. All delivery and perinatal outcomes analyzed were significantly different among the nine phenotypes. The whole SGA cohort had a three-times higher risk of perinatal mortality compared with non-SGA fetuses (1.4% vs 0.4%; P < 0.001). SGA clinical phenotypes exhibited three patterns of perinatal mortality risk: the highest risk was associated with congenital anomaly (8.3%; OR, 17.17 (95% CI, 2.17-136.12)) and second- or third-trimester hemorrhage (8.3%; OR, 9.94 (95% CI, 1.23-80.02)) clusters; medium risk was associated with gestational diabetes (3.8%; OR, 9.59 (95% CI, 1.27-72.57)), preterm birth (3.2%; OR, 4.65 (95% CI, 0.62-35.01)) and intrauterine growth restriction (3.1%; OR, 5.93 (95% CI, 3.21-10.95)) clusters; and the lowest risk was associated with the remaining clusters. Perinatal mortality rate did not differ between SGA fetuses without other clinical conditions (54.1% of SGA fetuses) and appropriate-for-gestational-age fetuses (0.1% vs 0.4%; OR, 0.41 (95% CI, 0.06-2.94); P = 0.27). SGA combined with other obstetric pathologies increased significantly the risk of perinatal mortality, as demonstrated by the increased odds of perinatal death in SGA cases with gestational diabetes compared to non-SGA cases with the same condition (OR, 24.40 (95% CI, 1.31-453.91)). CONCLUSIONS: We identified nine SGA clinical phenotypes associated with different patterns of risk for adverse perinatal outcome. Our findings suggest that considering clinical characteristics in addition to ultrasound findings could improve risk stratification and decision-making for management of SGA fetuses. Future clinical trials investigating management of fetuses with SGA should take into account clinical information in addition to Doppler parameters and estimated fetal weight. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

STATIN trial: predictive performance of competing-risks model in screening for pre-eclampsia at 35-37 weeks' gestation.

OBJECTIVE: To examine the predictive performance of a previously reported competing-risks model of screening for pre-eclampsia (PE) at 35-37 weeks' gestation by combinations of maternal risk factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1) in a validation dataset derived from the screened population of the STATIN study. METHODS: This was a prospective third-trimester multicenter study of screening for PE in singleton pregnancies by means of a previously reported algorithm that combines maternal risk factors and biomarkers. Women in the high-risk group were invited to participate in a trial of pravastatin vs placebo, but the trial showed no evidence of an effect of pravastatin in the prevention of PE. Patient-specific risks of delivery with PE were calculated using the competing-risks model, and the performance of screening for PE by maternal risk factors alone and by various combinations of risk factors with MAP, UtA-PI, PlGF and sFlt-1 was assessed. The predictive performance of the model was examined by, first, the ability of the model to discriminate between the PE and no-PE groups using the area under the receiver-operating-characteristics curve (AUC) and the detection rate at a fixed false-positive rate of 10%, and, second, calibration by measurements of calibration slope and calibration-in-the-large. RESULTS: The study population of 29 677 pregnancies contained 653 that developed PE. In screening for PE by a combination of maternal risk factors, MAP, PlGF and sFlt-1 (triple test), the detection rate at a 10% false-positive rate was 79% (95% CI, 76-82%) and the results were consistent with the data used for developing the algorithm. Addition of UtA-PI did not improve the prediction provided by the triple test. The AUC for the triple test was 0.923 (95% CI, 0.913-0.932), demonstrating very high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 0.875 (95% CI, 0.831-0.919), demonstrating good agreement between the predicted risk and observed incidence of PE. CONCLUSION: The competing-risks model provides an effective and reproducible method for third-trimester prediction of term PE. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of pre-eclampsia in twin pregnancy by maternal factors and biomarkers at 11-13 weeks' gestation: data from EVENTS trial.

OBJECTIVES: First, to validate a previously developed model for screening for pre-eclampsia (PE) by maternal characteristics and medical history in twin pregnancies; second, to compare the distributions of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum pregnancy-associated plasma protein-A (PAPP-A) in twin pregnancies that delivered with PE to those in singleton pregnancies and to develop new models based on these results; and, third, to examine the predictive performance of these models in screening for PE with delivery at < 32 and < 37 weeks' gestation. METHODS: Two datasets of prospective non-intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation were used. The first dataset was from the EVENTS (Early vaginal progesterone for the preVention of spontaneous prEterm birth iN TwinS) trial and the second was from a previously reported study that examined the distributions of biomarkers in twin pregnancies. Maternal demographic characteristics and medical history from the EVENTS-trial dataset were used to assess the validity of risks from our previously developed model. The combined data from the first and second datasets were used to compare the distributional properties of log10 multiples of the median (MoM) values of UtA-PI, MAP, PlGF and PAPP-A in twin pregnancies that delivered with PE to those in singleton pregnancies and develop new models based on these results. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE at < 32 and < 37 weeks' gestation. Screening performance was measured by detection rates (DR) and areas under the receiver-operating-characteristics curve. RESULTS: The EVENTS-trial dataset comprised 1798 pregnancies, including 168 (9.3%) that developed PE. In the validation of the prior model based on maternal characteristics and medical history, calibration plots demonstrated very good agreement between the predicted risks and the observed incidence of PE (calibration slope and intercept for PE < 32 weeks were 0.827 and 0.009, respectively, and for PE < 37 weeks they were 0.942 and -0.207, respectively). In the combined data, there were 3938 pregnancies, including 339 (8.6%) that developed PE and 253 (6.4%) that delivered with PE at < 37 weeks' gestation. In twin pregnancies that delivered with PE, MAP, UtA-PI and PlGF were, at earlier gestational ages, more discriminative than in singleton pregnancies and at later gestational ages they were less so. For PAPP-A, there was little difference between PE and unaffected pregnancies. The best performance of screening for PE was achieved by a combination of maternal factors, MAP, UtA-PI and PlGF. In screening by maternal factors alone, the DR, at a 10% false-positive rate, was 30.6% for delivery with PE at < 32 weeks' gestation and this increased to 86.4% when screening by the combined test; the respective values for PE < 37 weeks were 24.9% and 41.1%. CONCLUSIONS: In the assessment of risk for PE in twin pregnancy, we can use the same prior model based on maternal characteristics and medical history as reported previously, but in the calculation of posterior risks it is necessary to use the new distributions of log10 MoM values of UtA-PI, MAP and PlGF according to gestational age at delivery with PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

New approach for estimating risk of miscarriage after chorionic villus sampling.

OBJECTIVE: To estimate the risk of miscarriage associated with chorionic villus sampling (CVS). METHODS: This was a retrospective cohort study of women attending for routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation at one of eight fetal-medicine units in Spain, Belgium and Bulgaria, between July 2007 and June 2018. Two populations were included: (1) all singleton pregnancies undergoing first-trimester assessment at Hospital Clínico Universitario Virgen de la Arrixaca in Murcia, Spain, that did not have CVS (non-CVS group); and (2) all singleton pregnancies that underwent CVS following first-trimester assessment at one of the eight participating centers (CVS group). We excluded pregnancies diagnosed with genetic anomalies or major fetal defects before or after birth, those that resulted in termination and those that underwent amniocentesis later in pregnancy. We used propensity score (PS) matching analysis to estimate the association between CVS and miscarriage. We compared the risk of miscarriage of the CVS and non-CVS groups after PS matching (1:1 ratio). This procedure creates two comparable groups balancing the maternal and pregnancy characteristics that are associated with CVS, in a similar way to that in which randomization operates in a randomized clinical trial. RESULTS: The study population consisted of 22 250 pregnancies in the non-CVS group and 3613 in the CVS group. The incidence of miscarriage in the CVS group (2.1%; 77/3613) was significantly higher than that in the non-CVS group (0.9% (207/22 250); P < 0.0001). The PS algorithm matched 2122 CVS with 2122 non-CVS cases, of which 40 (1.9%) and 55 (2.6%) pregnancies in the CVS and non-CVS groups, respectively, resulted in a miscarriage (odds ratio (OR), 0.72 (95% CI, 0.48-1.10); P = 0.146). We found a significant interaction between the risk of miscarriage following CVS and the risk of aneuploidy, suggesting that the effect of CVS on the risk of miscarriage differs depending on background characteristics. Specifically, when the risk of aneuploidy is low, the risk of miscarriage after CVS increases (OR, 2.87 (95% CI, 1.13-7.30)) and when the aneuploidy risk is high, the risk of miscarriage after CVS is paradoxically reduced (OR, 0.47 (95% CI, 0.28-0.76)), presumably owing to prenatal diagnosis and termination of pregnancies with major aneuploidies that would otherwise have resulted in spontaneous miscarriage. For example, in a patient in whom the risk of aneuploidy is 1 in 1000 (0.1%), the risk of miscarriage after CVS will increase to 0.3% (0.2 percentage points higher). CONCLUSIONS: The risk of miscarriage in women undergoing CVS is about 1% higher than that in women who do not have CVS, although this excess risk is not solely attributed to the invasive procedure but, to some extent, to the demographic and pregnancy characteristics of the patients. After accounting for these risk factors and confining the analysis to low-risk pregnancies, CVS seems to increase the risk of miscarriage by about three times above the patient's background risk. Although this is a substantial increase in relative terms, in pregnancies without risk factors for miscarriage, the risk of miscarriage after CVS remains low and similar to, or slightly higher than, that in the general population. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Nuevo enfoque para estimar el riesgo de aborto después de una biopsia de vellosidades coriónicas OBJETIVO: Estimar el riesgo de aborto asociado con la biopsia de vellosidades coriónicas (BVC). MÉTODOS: Se trata de un estudio retrospectivo de cohorte de mujeres que acudieron a un examen ecográfico de rutina entre las 11+0 y las 13+6 semanas de gestación a una de entre un total de ocho centros de medicina fetal en España, Bélgica y Bulgaria, entre julio de 2007 y junio de 2018. En el estudio se incluyeron dos poblaciones: 1) todos los embarazos con feto único sometidos a evaluación del primer trimestre en el Hospital Clínico Universitario Virgen de la Arrixaca de Murcia (España), a las que no se les hizo una BVC (grupo no BVC); y 2) todos los embarazos con feto único sometidos a BVC tras la evaluación del primer trimestre en uno de los ocho centros participantes (grupo BVC). Se excluyeron los embarazos diagnosticados con anomalías genéticas o defectos fetales importantes antes o después del nacimiento, los que resultaron en una interrupción y los que más tarde se sometieron a amniocentesis durante el embarazo. Para estimar la relación entre la BVC y el aborto espontáneo se utilizó el pareamiento por puntaje de propensión (PPP). Se comparó el riesgo de aborto de los grupos BVC y no BVC después del pareamiento PPP (razón 1:1). Este procedimiento creó dos grupos comparables en los que las características de la madre y el embarazo que se asocian con la BVC estaban equilibradas, de manera similar a cómo funciona la aleatorización en un ensayo clínico aleatorizado. RESULTADOS: La población de estudio consistió en 22.250 embarazos en el grupo no BVC y 3.613 en el grupo BVC. La incidencia de abortos en el grupo BVC (2,1%; 77/3.613) fue significativamente mayor que en el grupo no BVC (0,9% (207/22.250); P<0,0001). El algoritmo del PPP emparejó 2.122 BVC con 2.122 casos no BVC, de los cuales 40 (1,9%) y 55 (2,6%) embarazos en los grupos BVC y no BVC, respectivamente, resultaron en un aborto espontáneo (razón de momios (RM), 0,72 (IC 95%, 0,48-1,10); P=0,146). Se encontró una interacción significativa entre el riesgo de aborto espontáneo después de una BVC y el riesgo de aneuploidía, lo que sugiere que el efecto de la BVC en el riesgo de aborto espontáneo difiere según las características del contexto. Concretamente, cuando el riesgo de aneuploidía es bajo, el riesgo de aborto después de una BVC aumenta (RM, 2,87 (IC 95%, 1,13-7,30)) y cuando el riesgo de aneuploidía es alto, paradójicamente el riesgo de aborto después de una BVC se reduce (RM, 0,47 (IC 95%, 0,28-0,76)), presumiblemente debido al diagnóstico prenatal y a la interrupción de embarazos con aneuploidías importantes que, de otro modo, hubieran provocado un aborto espontáneo. Por ejemplo, en una paciente para quien el riesgo de aneuploidía es de 1 entre 1000 (0,1%), el riesgo de aborto después de la BVC aumenta al 0,3% (0,2 puntos porcentuales más alto). CONCLUSIONES: El riesgo de aborto espontáneo en las mujeres que se someten a una BVC es aproximadamente un 1% mayor que el de las mujeres a las que no se les hace, aunque este exceso de riesgo no se atribuye únicamente al procedimiento agresivo sino, en cierta medida, a las características demográficas y del embarazo de cada paciente. Después de tener en cuenta estos factores de riesgo y limitar el análisis a los embarazos de bajo riesgo, la BVC parece triplicar aproximadamente el riesgo de aborto en comparación con el riesgo de fondo de la paciente. Aunque se trata de un aumento sustancial en términos relativos, en los embarazos sin factores de riesgo de aborto, después de una BVC el riesgo de aborto sigue siendo bajo y similar, o ligeramente superior, al de la población en general. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Synthesis and evaluation of HfO2 as a prospective filler in inorganic-organic hybrid membranes based on Nafion for PEM fuel cells.

Hybrid inorganic-organic Nafion membranes modified with metal oxides (typically TiO2, ZrO2, WO3) are a good alternative for fuel cell applications. However, one of their main limitations is associated with their relative low proton conductivity at temperatures above 80 °C. In this work, we overcome this issue using HfO2 as a filler. HfO2 was prepared by a sol-gel method, and it was compared with a recast Nafion membrane (named as recast). Deconvolved XPS spectra confirmed the presence of hafnia, while EDS analysis was used to determine its weight content resulting in a 1.88 wt%. FT-IR ATR experiments indicated that the HfO2 hybrid membrane possess a higher capability to retain water than the recast. Thus, the water uptake, swelling degree, conductivity tests and fuel cell evaluations were performed. The water uptake analysis revealed that the hybrid membrane presented a higher retention percentage at 100 °C (61%) than recast (29%). This improvement enabled a higher ionic conductivity at 80 °C and 100 °C. The hybrid membrane displayed a higher conductivity at 100 °C than the recast membrane (112 versus 82 mS cm-1), increasing the cell performance to 0.36 W cm-2; being this performance almost two-fold higher to that obtained for the recast membrane. In summary, herein we demonstrated that HfO2 can be considered as an excellent substitute to conventional fillers.

ASPRE trial: incidence of preterm pre-eclampsia in patients fulfilling ACOG and NICE criteria according to risk by FMF algorithm.

OBJECTIVE: To report the incidence of preterm pre-eclampsia (PE) in women who are screen positive according to the criteria of the National Institute for Health and Care Excellence (NICE) and the American College of Obstetricians and Gynecologists (ACOG), and compare the incidence with that in those who are screen positive or screen negative by The Fetal Medicine Foundation (FMF) algorithm. METHODS: This was a secondary analysis of data from the ASPRE study. The study population consisted of women with singleton pregnancy who underwent prospective screening for preterm PE by means of the FMF algorithm, which combines maternal factors and biomarkers at 11-13 weeks' gestation. The incidence of preterm PE in women fulfilling the NICE and ACOG criteria was estimated; in these patients the incidence of preterm PE was then calculated in those who were screen negative relative to those who were screen positive by the FMF algorithm. RESULTS: A total of 34 573 women with singleton pregnancy delivering at ≥ 24 weeks' gestation underwent prospective screening for preterm PE, of which 239 (0.7%) cases developed preterm PE. At least one of the ACOG criteria was fulfilled in 22 287 (64.5%) pregnancies and the incidence of preterm PE was 0.97% (95% CI, 0.85-1.11%); in the subgroup that was screen positive by the FMF algorithm the incidence of preterm PE was 4.80% (95% CI, 4.14-5.55%), and in those that were screen negative it was 0.25% (95% CI, 0.18-0.33%), with a relative incidence in FMF screen negative to FMF screen positive of 0.051 (95% CI, 0.037-0.071). In 1392 (4.0%) pregnancies, at least one of the NICE high-risk criteria was fulfilled, and in this group the incidence of preterm PE was 5.17% (95% CI, 4.13-6.46%); in the subgroups of screen positive and screen negative by the FMF algorithm, the incidence of preterm PE was 8.71% (95% CI, 6.93-10.89%) and 0.65% (95% CI, 0.25-1.67%), respectively, and the relative incidence was 0.075 (95% CI, 0.028-0.205). In 2360 (6.8%) pregnancies fulfilling at least two of the NICE moderate-risk criteria, the incidence of preterm PE was 1.74% (95% CI, 1.28-2.35%); in the subgroups of screen positive and screen negative by the FMF algorithm the incidence was 4.91% (95% CI, 3.54-6.79%) and 0.42% (95% CI, 0.20-0.86%), respectively, and the relative incidence was 0.085 (95% CI, 0.038-0.192). CONCLUSION: In women who are screen positive for preterm PE by the ACOG or NICE criteria but screen negative by the FMF algorithm, the risk of preterm PE is reduced to within or below background levels. The results provide further evidence to support the personalized risk-based screening method that combines maternal factors and biomarkers. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation.

OBJECTIVE: To examine the performance of screening for early, preterm and term pre-eclampsia (PE) at 11-13 weeks' gestation by maternal factors and combinations of mean arterial pressure (MAP), uterine artery (UtA) pulsatility index (PI), serum placental growth factor (PlGF) and serum pregnancy-associated plasma protein-A (PAPP-A). METHODS: The data for this study were derived from three previously reported prospective non-intervention screening studies at 11 + 0 to 13 + 6 weeks' gestation in a combined total of 61 174 singleton pregnancies, including 1770 (2.9%) that developed PE. Bayes' theorem was used to combine the prior distribution of gestational age at delivery with PE, obtained from maternal characteristics, with various combinations of biomarker multiples of the median (MoM) values to derive patient-specific risks of delivery with PE at < 37 weeks' gestation. The performance of such screening was estimated. RESULTS: In pregnancies that developed PE, compared to those without PE, the MoM values of UtA-PI and MAP were increased and those of PAPP-A and PlGF were decreased, and the deviation from normal was greater for early than late PE for all four biomarkers. Combined screening by maternal factors, UtA-PI, MAP and PlGF predicted 90% of early PE, 75% of preterm PE and 41% of term PE, at a screen-positive rate of 10%; inclusion of PAPP-A did not improve the performance of screening. The performance of screening depended on the racial origin of the women; on screening by a combination of maternal factors, MAP, UtA-PI and PlGF and using a risk cut-off of 1 in 100 for PE at < 37 weeks in Caucasian women, the screen-positive rate was 10% and detection rates for early, preterm and term PE were 88%, 69% and 40%, respectively. With the same method of screening and risk cut-off in women of Afro-Caribbean racial origin, the screen-positive rate was 34% and detection rates for early, preterm and term PE were 100%, 92% and 75%, respectively. CONCLUSION: Screening by maternal factors and biomarkers at 11-13 weeks' gestation can identify a high proportion of pregnancies that develop early and preterm PE. © 2018 Crown copyright. Ultrasound in Obstetrics & Gynecology © 2018 ISUOG.

Genitourinary syndrome of menopause. Prevalence and quality of life in Spanish postmenopausal women. The GENISSE study.

OBJECTIVE: To determine the prevalence of genitourinary syndrome of menopause (GSM) and urogynecological conditions associated with menopause, and to evaluate the impact of GSM on quality of life in a cohort of Spanish postmenopausal women. METHODS: Multicenter, cross-sectional, and observational study involving 430 women. RESULTS: The prevalence of GSM was 70%. GSM was diagnosed in 60.2% of women with no known diagnosis of vulvovaginal atrophy or GSM. Most prevalent symptoms were vaginal dryness (93.3%) and reduced lubrication with sexual activity (90.0%). Most prevalent signs were decreased moisture (93.7%) and loss of vaginal rugae (78.4%). GSM was significantly associated with stress or mixed urinary incontinence, overactive bladder, and vaginal prolapse. Symptoms showed a low-moderate impact on quality of life, mainly in sexual functioning and self-concept and body image. CONCLUSIONS: The GSM is very prevalent in Spanish postmenopausal women, affecting up to 70% of those consulting the gynecologist. Despite the high prevalence of symptoms and signs and its impact on the women's well-being, GSM remains underdiagnosed and undertreated. Given its relationship with urogynecological conditions, it seems necessary to provide an adequate evaluation of postmenopausal women for identifying potential co-morbidities and providing most adequate treatments. An adequate management of GSM will contribute to an improvement in the quality of life of these women.

sFlt-1/PlGF for prediction of early-onset pre-eclampsia: STEPS (Study of Early Pre-eclampsia in Spain).

OBJECTIVE: A high ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) has been linked to pre-eclampsia (PE). We evaluated the sFlt-1/PlGF ratio as a predictive marker for early-onset PE in women at risk of PE. METHODS: This prospective, Spanish, multicenter study included pregnant women with a risk factor for PE, including intrauterine growth restriction, PE, eclampsia or hemolysis, elevated liver enzymes and low platelet count syndrome in previous pregnancy, pregestational diabetes or abnormal uterine artery Doppler. The primary objective was to show that the sFlt-1/PlGF ratio at 20, 24 and 28 weeks' gestation was predictive of early-onset PE (< 34 + 0 weeks). Serum sFlt-1 and PlGF were measured at 20, 24 and 28 weeks. Multivariate logistic regression was used to develop a predictive model. RESULTS: A total of 819 women were enrolled, of which 729 were suitable for analysis. Of these, 78 (10.7%) women developed PE (24 early onset and 54 late onset). Median sFlt-1/PlGF ratio at 20, 24 and 28 weeks was 6.3 (interquartile range (IQR), 4.1-9.3), 4.0 (IQR, 2.6-6.3) and 3.3 (IQR, 2.0-5.9), respectively, for women who did not develop PE (controls); 14.5 (IQR, 5.5-43.7), 18.4 (IQR, 8.2-57.9) and 51.9 (IQR, 11.5-145.6) for women with early-onset PE; and 6.7 (IQR, 4.6-9.9), 4.7 (IQR, 2.8-7.2) and 6.0 (IQR, 3.8-10.5) for women with late-onset PE. Compared with early-onset PE, the sFlt-1/PlGF ratio was significantly lower in controls (P < 0.001 at each timepoint) and in women with chronic hypertension (P < 0.001 at each timepoint), gestational hypertension (P < 0.001 at each timepoint) and late-onset PE (P < 0.001 at each timepoint). A prediction model for early-onset PE was developed, which included the sFlt-1/PlGF ratio plus mean arterial pressure, being parous and previous PE, with areas under the receiver-operating characteristics curves of 0.86 (95% CI, 0.77-0.95), 0.91 (95% CI, 0.85-0.97) and 0.93 (95% CI, 0.86-0.99) at 20, 24 and 28 weeks, respectively, and was superior to models using the sFlt-1/PlGF ratio alone or uterine artery mean pulsatility index. CONCLUSIONS: The sFlt-1/PlGF ratio can improve prediction of early-onset PE for women at risk of this condition. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

PET-CT in presurgical lymph node staging in non-small cell lung cancer: the importance of false-negative and false-positive findings. / La PET-TC en la estadificación ganglionar prequirúrgica del carcinoma de pulmón de células no pequeñas: implicación de los falsos negativos y falsos positivos.

OBJECTIVE: To assess the importance of false-negative and false-positive findings in computed tomography (CT) and 18F-FDG positron emission tomography (PET) in mediastinal lymph node staging in patients undergoing surgery for non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: This retrospective study included 113 consecutive patients and 120 resected NSCLCs; 22 patients received neoadjuvant treatment. We compared the findings on preoperative 18F-FDG PET-CT studies with the postoperative pathology findings. Lymph node size and primary tumor size were measured with CT, and lymph nodes and primary tumors were evaluated qualitatively and semiquantitatively (using standardized uptake values (SUVmax)) with PET. RESULTS: Metastatic lymph nodes were found in 26 (21.7%) of the 120 tumors and in 41 (7.7%) of the 528 lymph node stations analyzed. 18F-FDG PET-CT yielded 53.8% sensitivity, 76.6% specificity, 38.9% positive predictive value, 85.7% negative predictive value, and 71.7% diagnostic accuracy. The false-negative rate was 14.2%. Multivariable analysis found that the factors associated with false-negative findings were a moderate degree of differentiation in the primary tumor (p = 0.005) and an SUVmax of the primary tumor >4 (p = 0.027). The false-positive rate was 61.1%, and the multivariable analysis found that lymph node size >1cm was associated with false-positive findings (p < 0.001). CONCLUSIONS: In mediastinal lymph node staging in patients with NSCLC, 18F-FDG PET-CT improves the specificity and negative predictive value and helps clinicians to select the patients that will benefit from surgery. Given the high rate of false positives, histological confirmation of positive cases is recommendable.

Pharmacokinetics and preliminary efficacy of two vaginal gel formulations of ultra-low-dose estriol in postmenopausal women.

OBJECTIVES: To investigate the pharmacokinetics, safety and preliminary effectiveness of ultra-low-dose estriol vaginal gel formulations (20 µg/g (T1) and 50 µg/g (T2)) compared to Ovestinon® (estriol 500 µg/0.5 g (R)) and placebo in postmenopausal women. METHODS: Forty-three volunteers were randomly assigned to received T1, T2, R or placebo once daily for 21 days. Absorption of estriol after single and multiple administration was analyzed. Cytological changes in the vagina, tolerability and safety were also investigated. RESULTS: Thirty-six women were included in the pharmacokinetic analysis. Systemic absorption was lower with test formulations (AUC0-t: 171.65 ± 80.18 (T1) and 406.75 ± 199.53 (T2) pg/ml × h) than with Ovestinon® (1221.97 ± 549.06 pg/ml × h). Estriol exposure of the test formulations after multiple administration (AUCss: 36.33 ± 30.52 (T1) and 73.71 ± 46.86 (T2) pg/ml × h) was significantly lower than after single-dose administration and not significantly different between them. In contrast, the exposure after repeated administration of Ovestinon® was considerable and not statistically different from levels after single administration. All estriol formulations produced similar improvement in the vaginal maturation value, while placebo showed a small and not significant change. Overall safety and acceptability were good. CONCLUSIONS: Estriol 20 and 50 µg/g formulations, while showing a comparable capacity for reversing vaginal atrophy, present a highly favorable safety profile, producing a very low systemic absorption of estriol and significantly lower than that of Ovestinon®.

[Long-term clinical and radiological results of metatarsophalangeal resection arthroplasty in patients with large forefoot deformities]. / Resultados clínicos y radiológicos a largo plazo de la artroplastía de resección metatarsofalángica en pacientes con grandes deformidades del antepié.

INTRODUCTION: metatarsophalangeal resection arthroplasty is considered a salvage surgical procedure able to improve the quality of life of patients with major forefoot deformities. MATERIAL AND METHODS: a retrospective observational study of 31 patients (36 feet) with major forefoot deformities operated at our institution was performed. Thirty two feet required additional surgery involving the first ray, most of them (72.2%) through MTP joint fusion. The mean follow-up period was 10.3 ± 4.6 years. Most patients were women (87.1%), the mean age was 74.2 ± 11.5 years. RESULTS: at the final follow-up, mean AOFAS score was 77.9 ± 10.2 points and mean MOxFQ score was 18.3 ± 8.3 points. Visual analog scale (VAS) for pain improved significantly from 7.5 ± 1.2 points to 3.4 ± 2.1 points on average. Good clinical results were also reported on ability to put on shoes comfortably. The mean resection arthroplasty spaces at the end of the study were 1.3, 1.8, 2.5 and 4.4 mm, for second to fifth rays, respectively. The mean sizes of remodeling osteophytes at the end of the study were 1.6, 1.4, 1.1 and 0.7 mm, respectively. Significant improvement was also achieved in the hallux valgus angle (HVA) and intermetatarsal angle (IMA) at the end of the study. CONCLUSION: in our experience, metatarsophalangeal resection arthroplasty continues to be a valid choice in patients with major forefoot deformities, with satisfactory long-term clinical and radiographic results.

INTRODUCCIÓN: la artroplastía de resección metatarsofalángica se considera un procedimiento quirúrgico de salvamento capaz de mejorar la calidad de vida de pacientes con deformidades importantes en el antepié. MATERIAL Y MÉTODOS: se realizó un estudio observacional retrospectivo de 31 pacientes (36 pies) con deformidades importantes en el antepié operados en nuestra institución. Treinta y dos pies requirieron cirugía adicional que involucró el primer metatarsiano, la mayoría de ellos (72.2%) a través de la fusión de la articulación metatarsofalángica. El período de seguimiento promedio fue 10.3 ± 4.6 años. La mayoría de los pacientes fueron mujeres (87.1%), con una edad promedio de 74.2 ± 11.5 años. RESULTADOS: en la última visita de seguimiento, la puntuación AOFAS promedio fue de 77.9 ± 10.2 puntos y la puntuación MOxFQ promedio fue de 18.3 ± 8.3 puntos. La escala visual analógica (EVA) para el dolor mejoró significativamente, pasando de 7.5 ± 1.2 puntos a 3.4 ± 2.1 puntos de media. También se constataron buenos resultados clínicos en cuanto a la capacidad de calzarse con comodidad. Los espacios de resección promedio al final del estudio fueron 1.3, 1.8, 2.5 y 4.4 mm para el segundo al quinto radio, respectivamente. Los tamaños promedio de los osteofitos por remodelación al final del estudio fueron de 1.6, 1.4, 1.1 y 0.7 mm, respectivamente. También se logró una mejora significativa en el ángulo de hallux valgus (AHV) y en el ángulo intermetatarsiano (IMA) al final del estudio. CONCLUSIÓN: en nuestra experiencia, la artroplastía de resección metatarsofalángica sigue siendo una opción válida en pacientes con deformidades graves del antepié, con resultados clínicos y radiográficos satisfactorios a largo plazo.

Metabolic characterization of structural lung changes in patients with findings suggestive of incidental COVID-19 pneumonia on 18F-FDG PET/CT. Pathophysiological insights from multimodal images obtained during the pandemic.

PURPOSE: To evaluate the metabolic uptake of different tomographic signs observed in patients with incidental structural findings suggestive of COVID-19 pneumonia through 18F-FDG PET/CT. MATERIALS AND METHODS: We retrospectively analyzed 596 PET/CT studies performed from February 21, 2020 to April 17, 2020. After excluding 37 scans (non-18F-FDG PET tracers and brain studies), we analyzed the metabolic activity of several structural changes integrated in the CO-RADS score using the SUVmax of multimodal studies with 18F-FDG. RESULTS: Forty-three patients with 18F-FDG PET/CT findings suggestive of COVID-19 pneumonia were included (mean age: 68±12.3 years, 22 male). SUVmax values were higher in patients with CO-RADS categories 5-6 than in those with lower CO-RADS categories (6.1±3.0 vs. 3.6±2.1, p=0.004). In patients with CO-RADS 5-6, ground-glass opacities, bilaterality and consolidations exhibited higher SUVmax values (p-values of 0.01, 0.02 and 0.01, respectively). Patchy distribution and crazy paving pattern were also associated with higher SUVmax (p-values of 0.002 and 0.01). After multivariate analysis, SUVmax was significantly associated with a positive structural diagnosis of COVID-19 pneumonia (odds ratio=0.63, 95% confidence interval=0.41-0.90; p=0.02). The ROC curve of the regression model intended to confirm or rule out the structural diagnosis of COVID-19 pneumonia showed an AUC of 0.77 (standard error=0.072, p=0.003). CONCLUSIONS: In those patients referred for standard oncologic and non-oncologic indications (43/559; 7.7%) during pandemic, imaging with 18F-FDG PET/CT is a useful tool during incidental detection of COVID-19 pneumonia. Several CT findings characteristic of COVID-19 pneumonia, specifically those included in diagnostic CO-RADS scores (5-6), were associated with higher SUVmax values.

Evaluation of rectus abdominis muscle strength and width of hernia defect in patients undergoing incisional hernia surgery.

BACKGROUND: The aim of this study was to analyze the strength status of the rectus abdominis muscle in patients with incisional hernia and the relationship between the width of the hernia defect and the strength of the rectus abdominis muscle. METHODS: This is a observational cohort study of patients with medial line incisional hernia (July-October 2022), classified as W2 according to the European Hernia Society (EHS). The data collected were demographic and clinical characteristics related to hernia, and measure of the rectus abdominis muscle strength using an isokinetic dynamometer and a strain gauge. We analyzed the relationship between hernia width and rectus abdominis muscle strength with correlation tests to adjustment by age, sex, BMI, and body composition. RESULTS: A total of 40 patients (64% female) with a mean age of 57.62 years (SD 11) were enrolled in the study. The mean BMI was 29.18 (SD 5.06), with a mean percentage of fat mass of 37.8% (SD 8.47) and a mean percentage of muscle mass of 60.33% (SD 6.43). The maximum width of the hernia defect was 6.59 cm (SD 1.54). In the male group, the mean bending force moment (ISOK_PT) was 94.01 Nw m (SD 34.58), bending force moment relative to body weight (ISOK_PT_Weight) was 103.32 Nw m (SD 37.48), and peak force (PK_90) was 184.71 N (SD 47.01). In the female group, these values were 58.11 Nw m (SD 29.41), 66.48 Nw m (SD 32.44), and 152.50 N (SD 48.49), respectively. Statistically significant differences were observed in the relationship between the data obtained with the isokinetic dynamometer and sex (p = 0.002), as well as between the data obtained with the isokinetic dynamometer and age (p = 0.006). Patients in the 90th percentile (P90) of rectus abdominis muscle strength also had smaller hernia defect widths (p = 0.048). CONCLUSIONS: In this study, age and sex were identified as the most statistically significant predictor variables for rectus abdominis muscle strength. The width of the hernia defect exhibited a trend towards statistical significance.

Clinical impact of (18)F-FDG PET in management of patients with renal cell carcinoma.

We performed a retrospective study to evaluate the accuracy, diagnostic validity, and clinical impact of (18)F-FDG PET in the management of recurrent and metastatic disease in patients with Renal Cell Carcinoma (RCC) from our database. (18)F-FDG PET studies were identified from 58 patients that matched our criteria for inclusion in the study. Results were confirmed with histopathological findings, clinical follow-up time (at least 12 months), and/ or conventional imaging methods (CIM). A sensitivity of 80.56%, specificity 86.36%, diagnostic accuracy 58.7%, positive predictive value 90.63%, and a negative predictive value of 73.08% were observed. The clinical impact was high in 25 cases (43%) and we found no impact in only 10 studies (17.2%). We concluded that (18)F-FDG PET was useful and had a high clinical impact in the management of recurrent and metastatic RCC. From our data, it seemed that a positive PET study was more helpful to the physician than a negative study.

Composite Sulfonated Polyether-Ether Ketone Membranes with SBA-15 for Electrochemical Energy Systems.

The aim of this work is the evaluation of a Sulfonated Poly Ether-Ether Ketone (S-PEEK) polymer modified by the addition of pure Santa Barbara Amorphous-15 (SBA-15, mesoporous silica) and SBA-15 previously impregnated with phosphotungstic acid (PWA) fillers (PWA/SBA-15) in order to prepare composite membranes as an alternative to conventional Nafion® membranes. This component is intended to be used as an electrolyte in electrochemical energy systems such as hydrogen and methanol Proton Exchange Membrane Fuel Cell (PEMFC) and Electrochemical Hydrogen Pumping (EHP). The common requirements for all the applications are high proton conductivity, thermomechanical stability, and fuel and oxidant impermeability. The morphology of the composite membranes was investigated by Scanning Electron Microscopy- Energy Dispersive X-ray Spectroscopy (SEM-EDS) analysis. Water Uptake (Wup), Ion Exchange Capacity (IEC), proton conductivity, methanol permeability and other physicochemical properties were evaluated. In PEMFC tests, the S-PEEK membrane with a 10 wt.% SBA-15 loading showed the highest performance. For EHP, the inclusion of inorganic materials led to a back-diffusion, limiting the compression capacity. Concerning methanol permeability, the lowest methanol crossover corresponded to the composites containing 5 wt.% and 10 wt.% SBA-15.

Contralateral axillary sentinel lymph node drainage in breast cancer: Controversies and management according to the literature. A case report. / Drenaje del ganglio centinela a axila contralateral en cáncer de mama: controversias y manejo según la literatura. A propósito de un caso.

Lymphoscintigraphy in breast cancer usually shows lymphatic drainage to the ipsilateral axilla. Drainage to extraaxillary or contralateral axillary regions is rare and there is still controversy about its management. Due to the significant clinical impact of an accurate staging, a literature research is made based on a case of a patient with recurrence of left breast cancer with contralateral axillary sentinel lymph node detection, without evidence of lymphatic drainage to other locations.