Lower uterine segment scar assessment at 11-14 weeks' gestation to screen for placenta accreta spectrum in women with prior Cesarean delivery.

OBJECTIVES: To validate prospectively transvaginal ultrasound assessment of the lower uterine segment (LUS) scar at the time of first-trimester screening in women with previous Cesarean section (CS) and to determine its feasibility and accuracy in stratifying women according to the risk for placenta accreta spectrum (PAS) disorder. METHODS: Women with a history of CS were recruited between 11 + 0 and 13 + 6 weeks' gestation and underwent LUS scar assessment using transvaginal ultrasound. A standardized midsagittal plane, which included the cervicoisthmic canal (CIC), the uterine scar and the placental site, was obtained. The scar was described in terms of its size (narrow or dehiscent) and its location in relation to the CIC (within or above), with each LUS scar classified into one of four groups based on these features. Placental location was assessed and classified as high- or low-lying. Women were stratified according to the risk of PAS, based on the relationship between the scar location and placental site. Women were considered high risk when the scar was above the CIC and the placenta was low-lying (i.e. when the placenta was overlying an exposed scar) and low risk when the scar was within the CIC and/or the placenta was high. High-risk patients were followed up at 20 weeks and 28-30 weeks for the development of PAS. Maternal demographics, detailed obstetric history and obstetric outcome were collected. RESULTS: First-trimester transvaginal ultrasound was offered to 535 women with prior CS during the study period. A LUS scar was visualized in 79.9% (401/502) of those who agreed to undergo the examination. At this scan, the LUS scar was above the CIC in 9.0% (36/401) of women, but only 5.7% (23/401) additionally had a low-lying placenta overlying the scar. Of these 23 high-risk women, two were found to have PAS on the mid-trimester screening scan and one was noted to have placental adherence during evacuation following mid-trimester termination of pregnancy. On the first-trimester scan, 94.3% (378/401) of women were at low risk of PAS. This screening protocol yielded a positive likelihood ratio of 21.33 (95% CI, 13.02-34.96), sensitivity of 100% (95% CI, 29.24-100%), specificity of 95.31% (95% CI, 92.39-97.35%), positive predictive value of 16.7% (95% CI, 5.8-39.2%) and negative predictive value of 100% (95% CI, 98.4-100%). On multivariable regression analysis performed to identify confounding variables associated with a LUS scar above the CIC, only maternal body mass index ≥ 30 kg/m2 was significant (odds ratio (OR), 2.42 (95% CI, 1.04-5.39); P = 0.03). Although there was a trend towards an increased risk of a LUS scar above the CIC in women with prior elective prelabor CS (OR, 1.72 (95% CI, 0.80-3.68)), this association did not reach statistical significance. CONCLUSIONS: Routine transvaginal ultrasound assessment of the location of the LUS scar and placenta at the time of first-trimester screening between 11 + 0 and 13 + 6 weeks' gestation in women with prior CS is a feasible and effective tool to identify those at risk of subsequent development of PAS disorder. A finding of placental implantation over an exposed LUS scar seems to be cardinal in predicting the risk of PAS disorder in women with prior CS, with an excellent negative predictive value. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

[A clinical management protocol for COVID-19 infection in pregnant women]. / Guía de actuación para el manejo de la infección por COVID-19 durante en el embarazo.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has caused a large global outbreak and has had a major impact on health systems and societies worldwide. The generation of knowledge about the disease has occurred almost as fast as its global expansion. Very few studies have reported on the effects of the infection on maternal health, since its onset. The mother and foetus do not seem to be at particularly high risk. Nevertheless, obstetrics and maternal-foetal medicine practice have made profound changes in order to adapt to the pandemic. In addition, there are aspects specific to COVID-19 and gestation that should be known by specialists. In this review an evidenced-based protocol is presented for the management of COVID-19 in pregnancy.

Yin-Yang 1 transcription factor modulates ST2 expression during adverse cardiac remodeling post-myocardial infarction.

BACKGROUND: The cardioprotective effects of metformin remain poorly defined. Interleukin (IL)-33/ST2L signaling is a novel cardioprotective pathway, which is antagonized by the soluble isoform sST2. No data exist about the regulation of ST2 expression. This study aimed to evaluate the pathophysiological implication of Yin-Yang 1 (Yy1) transcription factor in cardiac remodeling and the expression of the soluble ST2 isoform. METHODS AND RESULTS: Myocardial infarction (MI) was induced in Wistar rats randomly receiving metformin or saline solution by permanent ligation of the left anterior coronary artery. In addition, a model of cardiomyocyte "biochemical strain" was used. Metformin administration improved post-MI cardiac remodeling, an effect that was associated with increased IL-33 and reduced sST2 levels in the myocardium. The anti-remodeling effects of metformin were also associated with a decrease in the transcription factor Yy1 intranuclear level and lower levels of phosphorylated HDAC4 within the cytoplasmic space. These effects were also observed in a cardiomyocyte biochemical strain model, where Yy1 silencing or HDAC4 inhibition blocked sST2 production in cardiomyocytes. Metformin blocked the HDAC4 phosphorylation induced by MI, preventing its export from the nucleus to the cytosol. The presence of dephosphorylated HDAC4 in the nucleus acted as a co-repressor of Yy1, repressing sST2 expression. CONCLUSION: The transcription factor Yy1 regulates sST2 expression, and repression of Yy1 by metformin results in lower levels of sST2 that are associated with favorable myocardial remodeling. The manipulation of YY1 or its co-repressor HDAC4 emerge as new targets to modulate ST2/IL33 signaling and prevent adverse cardiac remodeling.

Should phenotype of previous preterm birth influence management of women with short cervix in subsequent pregnancy? Comparison of vaginal progesterone and Arabin pessary.

OBJECTIVE: To investigate whether the classification of a previous spontaneous preterm birth (sPTB) as preterm labor (PTL) with intact membranes (IM) or as preterm prelabor rupture of membranes (PPROM) impacts the efficacy of cervical pessary or vaginal progesterone for prevention of sPTB in pregnant women with short cervix on transvaginal ultrasound. METHODS: This was a retrospective cohort study of asymptomatic high-risk singleton pregnancies with a short cervix and history of sPTB, treated using Arabin pessary or vaginal progesterone for primary PTB prevention, conducted at four European hospitals. A log-rank test on Kaplan-Meier curves was used to assess the difference in performance of pessary and progesterone, according to history of PTL-IM or PPROM. Linear regression analysis was used to evaluate significant predictors of gestational age at delivery. RESULTS: Between 2008 and 2015, 170 women were treated with a pessary and 88 with vaginal progesterone. In women treated with a pessary, rate of sPTB < 34 weeks was 16% in those with a history of PTL-IM and 55% in those with a history of PPROM. In women treated with progesterone, rate of sPTB < 34 weeks was 13% in those with a history of PTL-IM and 21% in those with a history of PPROM. Treatment with a pessary resulted in earlier delivery in women with previous PPROM than in any other subgroup (P < 0.0001). Linear regression analysis showed a clear effect of PPROM history (P < 0.0001), combination of PPROM history and treatment (P = 0.0003) and cervical length (P = 0.0004) on gestational age at birth. CONCLUSIONS: Cervical pessary may be a less efficacious treatment option for women with previous PPROM; however, these results require prospective validation before change in practice is recommended. Phenotype of previous preterm birth may be an important risk predictor and treatment effect modifier; this information should be reported in future clinical trials. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Cervical consistency index and risk of Cesarean delivery after induction of labor at term.

OBJECTIVE: To evaluate the association between the cervical consistency index (CCI) and the risk of Cesarean delivery after planned induction of labor (IOL) at term. METHODS: This was a prospective observational study of women with a term singleton pregnancy admitted for IOL due to maternal or fetal indication. Ultrasonographic images were obtained before IOL and CCI was calculated offline once recruitment was completed. The main outcome was defined as Cesarean delivery due to failed IOL or arrest of labor. Cesarean deliveries indicated due to maternal or fetal compromise (Van Dillen's grade 1 or 2) were excluded from analysis. Univariate statistical analysis was performed using Fisher's exact test and Student's t-test for categorical and continuous variables, respectively. Multivariate analysis was performed using logistic regression, including CCI and other variables related to the main outcome. Intraclass correlation coefficients were used to estimate intra- and interobserver agreement. RESULTS: Of 510 women admitted for IOL during the study period and for whom image quality was adequate, 46 were excluded due to emergency Cesarean delivery leaving 464 pregnancies for analysis. Cesarean section due to failed IOL or arrest of labor was performed in 100/464 (21.6%) pregnancies. The mean CCI of women who underwent Cesarean delivery was not significantly different from that in those who had vaginal delivery after IOL (70.1 ± 12.3% vs 70.0 ± 13.1%; P = 0.94). Multivariate analysis also showed absence of statistical association between CCI and Cesarean delivery for failed IOL or arrest of labor. Intraclass correlation coefficients for intra- and interobserver agreement were 0.81 (95% CI, 0.66-0.89) and 0.86 (95% CI, 0.75-0.92), respectively. CONCLUSION: CCI does not seem to be associated with the risk of Cesarean delivery after IOL. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Mid-trimester sonographic cervical consistency index to predict spontaneous preterm birth in a low-risk population.

OBJECTIVES: To investigate the effectiveness of mid-trimester sonographic cervical consistency index (CCI) for the prediction of spontaneous preterm birth (sPTB) in low-risk pregnancies and to compare its performance with that of mid-trimester sonographic cervical-length (CL) measurement. METHODS: This was a prospective cohort study of women with a singleton pregnancy examined by ultrasound at 19 + 0 to 24 + 6 weeks' gestation. All women underwent transvaginal ultrasound examination of the cervix, but CCI and CL were measured, offline, only in women without a risk factor for sPTB. Staff and participants were blinded to CL and CCI results. CCI was obtained by calculating the ratio between the anteroposterior diameter of the uterine cervix at maximum compression and at rest. The primary outcome was prediction of sPTB before 37 + 0 weeks. Receiver-operating characteristics (ROC) curves were produced and sensitivity and specificity were calculated for the optimal cut-off based on the ROC curve and for the 1st , 5th and 10th centiles of CCI and CL. Intraclass correlation coefficients (ICC) and Bland-Altman plots were used to estimate intra- and interobserver agreement and reliability for measurement of CCI and CL. RESULTS: Of the 749 women who underwent ultrasound examination of the cervix, 532 were included for analysis. The rates of sPTB before 37 + 0 and before 34 + 0 weeks were 4.1% (22/532) and 1.3% (7/532), respectively. The rates of short cervix < 25 mm and ≤ 20 mm were 0.9% (5/532) and 0.4% (2/532), respectively. The area under the ROC curve (AUC) with regard to predicting sPTB before 37 + 0 weeks was 0.84 (95% CI, 0.75-0.93) for CCI compared with 0.68 (95% CI, 0.56-0.81) for CL (P = 0.03). The optimal cut-off based on the ROC curve was 64.6% for CCI (sensitivity, 77.3%; specificity, 82.7%) and that for CL was 37.9 mm (sensitivity, 72.7%; specificity, 61.2%). The AUC with regard to predicting sPTB before 34 + 0 weeks was 0.87 (95% CI, 0.71-1.0) for CCI compared with 0.71 (95% CI, 0.47-0.94) for CL (P = 0.25). The optimal cut-off based on the ROC curve was 63.6% for CCI (sensitivity, 85.7%; specificity, 84.0%) and that for CL was 37.9 mm (sensitivity, 85.7%; specificity, 61.3%). Intraobserver ICC was > 0.90 both for CCI and CL, while interobserver ICC was 0.89 for CCI and 0.90 for CL. CONCLUSIONS: Second-trimester CCI is a better predictor of sPTB < 37 weeks in low-risk pregnancies than is CL. External validation is needed as well as studies assessing the value of CCI as a screening tool in unselected and high-risk populations. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Quantitative analysis of cervical texture by ultrasound in mid-pregnancy and association with spontaneous preterm birth.

OBJECTIVE: New tools are required to improve the identification of women who are at increased risk for spontaneous preterm birth (sPTB). Quantitative analysis of tissue texture on ultrasound has been used to extract robust features from the ultrasound image to detect subtle changes in its microstructure. This may be applied to the cervix. The aim of this study was to determine if there is an association between quantitative analysis of cervical texture (CTx) on mid-trimester ultrasound and sPTB < 37 + 0 weeks' gestation. METHODS: This was a single-center nested case-control study of a prospective cohort of 677 consecutive women with singleton pregnancy assessed between 19 + 0 and 24 + 6 weeks' gestation. Women at increased risk for sPTB were included unless they received treatment to prevent sPTB. Women who delivered < 37 + 0 weeks (sPTB) were considered as cases and were matched in a 1: 10 ratio with randomly selected contemporary controls who delivered at term. For each woman, one ultrasound image of the cervix was obtained for which quality was assessed, cervical length (CL) measured offline and a region of interest in the midportion of the anterior cervical lip delineated for use in local binary patterns analysis of CTx. A learning algorithm was developed to obtain the combination of CTx features best associated with sPTB based on feature transformation and discriminant analysis regression. The ability of the learning algorithm to predict sPTB was evaluated using a leave-one-out cross-validation technique, which produced a CTx-based score for each participant. Receiver-operating characteristics (ROC) curves were produced and sensitivity, specificity, and positive and negative likelihood ratios were calculated for the optimal cut-off based on the ROC curve. The results were compared with those obtained for CL. Investigators studying the images were blinded to pregnancy outcome at all times. RESULTS: Images from 310 women (27 cases and 283 controls) were of sufficient quality and included in the study. Median CTx-based score was significantly lower in cases compared with controls (-1.01 vs -0.07, P ≤ 0.0001). CTx-based score maintained its significant association with sPTB after adjusting for possible confounders (history of sPTB, conization or Müllerian malformation, and CL < 25 mm). CTx-based score was a better predictor of sPTB (AUC, 0.77; 95% CI, 0.66-0.87) than was CL (AUC, 0.60; 95% CI, 0.47-0.72) (P = 0.03). Median CL was similar for cases and controls (37.7 vs 38.6 mm, P = 0.26), although cases were more likely to have CL < 25 mm (18.5% vs 0.4%, P < 0.001). CONCLUSION: Quantitative analysis of CTx enables the extraction of information relevant to sPTB from ultrasound images to generate a CTx-based score that is associated independently with sPTB. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Cervical length screening for prevention of preterm birth in singleton pregnancy with threatened preterm labor: systematic review and meta-analysis of randomized controlled trials using individual patient-level data.

OBJECTIVE: Cervical length screening by transvaginal sonography (TVS) has been shown to be a good predictive test for spontaneous preterm birth (PTB) in symptomatic singleton pregnancy with threatened preterm labor (PTL). The aim of this review and meta-analysis of individual participant data was to evaluate the effect of knowledge of the TVS cervical length (CL) in preventing PTB in singleton pregnancies presenting with threatened PTL. METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and the Cochrane Complementary Medicine Field's Trials Register (May 2016) and reference lists of retrieved studies. Selection criteria included randomized controlled trials of singleton gestations with threatened PTL randomized to management based mainly on CL screening (intervention group), or CL screening with no knowledge of results or no CL screening (control group). Participants included women with singleton gestations at 23 + 0 to 36 + 6 weeks with threatened PTL. We contacted corresponding authors of included trials to request access to the data and perform a meta-analysis of individual participant data. Data provided by the investigators were merged into a master database constructed specifically for the review. The primary outcome was PTB < 37 weeks. Summary measures were reported as relative risk (RR) or as mean difference (MD) with 95% CI. RESULTS: Three trials including a total of 287 singleton gestations with threatened PTL between 24 + 0 and 35 + 6 weeks were included in the meta-analysis, of which 145 were randomized to CL screening with knowledge of results and 142 to no knowledge of CL. Compared with the control group, women who were randomized to the known CL group had a significantly lower rate of PTB < 37 weeks (22.1% vs 34.5%; RR, 0.64 (95% CI, 0.44-0.94); three trials; 287 participants) and a later gestational age at delivery (MD, 0.64 (95% CI, 0.03-1.25) weeks; MD, 4.48 (95% CI, 1.18-8.98) days; three trials; 287 participants). All other outcomes for which there were available data were similar in the two groups. CONCLUSIONS: There is a significant association between knowledge of TVS CL and lower incidence of PTB and later gestational age at delivery in symptomatic singleton gestations with threatened PTL. Given that in the meta-analysis we found a significant 36% reduction in the primary outcome, but other outcomes were mostly statistically similar, further study needs to be undertaken to understand better whether the predictive characteristics of CL screening by TVS can be translated into better clinical management and therefore better outcomes and under what circumstances. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. CRIBADO MEDIANTE LA LONGITUD CERVICAL PARA LA PREVENCIÓN DEL PARTO PRETÉRMINO EN EMBARAZOS CON FETO ÚNICO Y RIESGO DE PARTO PREMATURO: REVISIÓN SISTEMÁTICA Y METAANÁLISIS DE ENSAYOS CONTROLADOS ALEATORIZADOS HACIENDO USO DE LOS DATOS INDIVIDUALES DE LAS PACIENTES: RESUMEN OBJETIVO: El cribado mediante la longitud cervical obtenida con ecografía transvaginal (ETV) ha demostrado ser una buena prueba para la predicción del parto pretérmino espontáneo (PPTE) en embarazos con feto único sintomáticos debido a la amenaza de parto pretérmino (PPT). El objetivo de esta revisión y metaanálisis de los datos de participantes individuales fue evaluar el efecto de medir la longitud cervical (LC) mediante ETV con el fin de prevenir el parto prematuro en embarazos únicos con amenaza de PPT. MÉTODOS: Se realizaron búsquedas en los ficheros de ensayos de Cochrane Pregnancy and Childbirth Group y Complementary Medicine Field (mayo de 2016), y en las listas de referencias de los estudios encontrados. Los criterios de selección incluyeron ensayos controlados aleatorizados de embarazos con feto único y riesgo de PPT con aleatorización de la paciente basada principalmente en el cribado mediante la LC (grupo de intervención), el cribado mediante la LC sin conocimiento de los resultados, o sin cribado de LC (grupo de control). Las participantes fueron mujeres embarazadas con feto único desde las 23 + 0 hasta las 36 + 6 semanas y con riesgo de PPT. Se estableció contacto con los autores de los ensayos incluidos para solicitar el acceso a los datos y llevar a cabo un metaanálisis de los datos de las participantes individualmente. Los datos proporcionados por los investigadores se agregaron a una base de datos maestra creada específicamente para esta revisión. El resultado primario fue el PPTE < 37 semanas. Las medidas resumen se reportaron como riesgo relativo (RR) o como diferencia de medias (DM) con IC del 95%. RESULTADOS: En el metaanálisis se incluyeron tres ensayos con un total de 287 embarazos con feto único y riesgo de PPT entre 24 + 0 y 35 + 6 semanas, de los cuales 145 fueron asignados al azar a un cribado mediante la LC con conocimiento de los resultados y 142 a aquellos para los que se desconocía la LC. En comparación con el grupo control, las mujeres que fueron asignadas aleatoriamente al grupo en el que se conocía la LC tuvieron una tasa de parto prematuro a < 37 semanas significativamente menor (22,1% vs. 34,5%; RR 0,64 (IC 95%, 0,44-0,94); 3 ensayos; 287 participantes ) y una edad gestacional al momento del parto más tardía (DM 0,64 (IC 95%, 0.03-1.25) semanas; DM 4,48 (IC 95%, 1,18-8,98) días; 3 ensayos; 287 participantes). El resto de los resultados para los cuales había datos disponibles fueron similares en ambos grupos. CONCLUSIONES: Existe una asociación significativa entre el conocimiento de la LC obtenida mediante ETV y una menor incidencia de PPTE y edad gestacional más tardía en el momento del parto en embarazos con feto único sintomáticos debido al riesgo de parto pretérmino (PPT). Teniendo en cuenta que en el metaanálisis se encontró una reducción significativa del 36% en el resultado primario, pero que los otros resultados fueron estadísticamente similares en su mayoría, serán necesarios más estudios para entender mejor si las propiedades predictivas del cribado mediante la LC obtenida con ETV se pueden traducir en una mejor atención clínica y por lo tanto mejores resultados dependiendo de las circunstancias. :META: : ,(preterm labor,PTL),(transvaginal sonography,TVS)(spontaneous preterm birth,PTB)。metaPTL,TVS(cervical length,CL)PTB。 : CochraneCochrane(20165)。PTL,CL()CLCL()。23 + 036+6PTL。,,meta。。37PTB。(relative risk,RR)95%CI(mean difference,MD)。 : meta3,28724 + 035+6PTL,145CL,142CL。,CL37PTB[22.1%34.5%;RR,0.64(95% CI,0.44 ~ 0.94);3;287],[MD,0.64(95% CI,0.03 ~ 1.25);MD,4.48(95% CI,1.18 ~ 8.98);3;287]。2,。 : PTL,TVS CLPTB。meta36%,,,TVSCL,。.

Postpartum two- and three-dimensional ultrasound evaluation of anal sphincter complex in women with obstetric anal sphincter injury.

OBJECTIVE: To compare the sensitivity and specificity of two- (2D) and three- (3D) dimensional transperineal ultrasound (TPUS) and 3D endovaginal ultrasound (EVUS) with the gold standard 3D endoanal ultrasound (EAUS) in detecting residual defects after primary repair of obstetric anal sphincter injuries (OASIS). METHODS: External (EAS) and internal (IAS) anal sphincters were evaluated by the four ultrasound modalities in women with repaired OASIS. 2D-TPUS was evaluated in real-time, whereas 3D-TPUS, 3D-EVUS and 3D-EAUS volumes were evaluated offline by six blinded readers. The presence/absence of any tear in EAS or IAS was recorded and defects were scored according to the Starck system. Sensitivity, specificity and predictive values were calculated, using 3D-EAUS as reference standard. Inter- and intraobserver analyses were performed for all 3D imaging modalities. Association between patients' symptoms (Wexner score) and ultrasound findings (Starck score) was calculated. RESULTS: Images from 55 patients were analyzed. Compared with findings on 3D-EAUS, the agreement for EAS evaluation was poor for 3D-EVUS (κ = 0.01), fair for 2D-TPUS (κ = 0.30) and good for 3D-TPUS (κ = 0.73). The agreement for IAS evaluation was moderate for both 3D-EVUS (κ = 0.41) and 2D-TPUS (κ = 0.52) and good for 3D-TPUS (κ = 0.66). Good intraobserver (3D-EAUS, κ = 0.73; 3D-TPUS, κ = 0.78) and interobserver (3D-EAUS, κ = 0.68; 3D-TPUS, κ = 0.60) agreement was reported. Significant association between Starck and Wexner scores was found only for 3D-EAUS (Spearman's rho = 0.277, P = 0.04). CONCLUSIONS: 2D-TPUS and 3D-EVUS are not accurate modalities for the assessment of anal sphincters after repair of OASIS. 3D-TPUS shows good agreement with the gold standard 3D-EAUS and a high sensitivity in detecting residual defects. It, thus, has potential as a screening tool after primary repair of OASIS. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Vaginal progesterone as maintenance treatment after an episode of preterm labour (PROMISE) study: a multicentre, double-blind, randomised, placebo-controlled trial.

OBJECTIVE: To evaluate whether maintenance treatment with vaginal progesterone after an arrested preterm labour reduces the incidence of preterm delivery. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. SETTING: Twelve tertiary care centres in Spain. POPULATION: A total of 265 women with singleton pregnancy, preterm labour successfully arrested with tocolytic treatment, and cervical length of <25 mm. METHODS: Randomisation was stratified by gestational age (from 24.0 to <31.0 weeks of gestation and from 31.0 to <34.0 weeks of gestation) and centre. Patients were randomly assigned, in a 1 : 1 ratio, to either daily vaginal capsules of 200 mg progesterone or placebo until delivery or 36.6 weeks of gestation, whichever occurred first. MAIN OUTCOME MEASURES: Primary outcome was delivery before 34.0 and 37.0 weeks of gestation. Secondary outcomes were discharge-to-delivery time, readmissions because of preterm labour, emergency service use, and neonatal morbidity and mortality. RESULTS: From June 2008 through June 2012, 1419 women were screened: 472 met the inclusion criteria and 265 were randomised. The final analysis included 258 women: 126 in the progesterone group and 132 in the placebo group. There were no significant differences between the progesterone and placebo groups in terms of delivery at <34 weeks of gestation [9/126 (7.1%) versus 10/132 (7.6%), P = 0.91] or <37 weeks of gestation [36/126 (28.6%) versus 29/132 (22.0%), P = 0.22]. There were no differences observed between groups when considering the two strata of gestational age at inclusion. CONCLUSIONS: A maintenance treatment of 200 mg of daily vaginal progesterone capsules in women discharged home after an episode of arrested preterm labour did not significantly reduce the rate of preterm delivery. TWEETABLE ABSTRACT: Maintenance progesterone in 258 women after arrested PTL showed no benefit.

Prevalence of honeybee viruses in different regions of China and Argentina.

Honeybees are threatened by various pathogens and parasites. More than 18 viruses have been described in honeybees and many of them have been detected in China and Argentina. In China, both Apis cerana and Apis mellifera are raised. In Argentina, beekeepers raise different ecotypes of A. mellifera: European honeybees (in both temperate and subtropical regions) and Africanised honeybees (in subtropical areas only). A thorough study was carried out in both China and Argentina to analyse the current virus presence and distribution in different climatic zones and gather information on different bee species/subspecies. Adult honeybees were collected from apiaries in temperate and subtropical regions of China (including areas with exclusive populations of A. mellifera, areas where A. mellifera and A. cerana co-exist, and areas with exclusive populations of A. cerana) and Argentina. Six viruses, namely, deformed wing virus (DWV), black queen cell virus (BQCV), sacbrood virus (SBV), chronic bee paralysis virus (CBPV), acute bee paralysis virus (ABPV) and Israeli acute paralysis virus (IAPV) were detected in China, both in A. cerana and in A. mellifera, while four viruses (DWV, BQCV, CBPV and ABPV) were present in Argentina. Interestingly, multiple infections were commonly found in China, with up to five different viruses co-circulating in some colonies without apparent abnormalities. In this study, no Chinese samples were positive for slow bee paralysis virus. The most prevalent viruses were BQCV (China) and DWV (Argentina). Kashmir bee virus was absent from samples analysed for both countries.

Les populations d'abeilles mellifères sont menacées par de nombreux agents pathogènes et parasites. Parmi eux, 18 virus ont été décrits, dont plusieurs ont été détectés en Chine et en Argentine. Les espèces d'abeilles mellifères élevées en Chine sont Apis cerana et Apis mellifera. En Argentine, les apiculteurs élèvent plusieurs écotypes d'A. mellifera : le type européen dans les régions tempérées et subtropicales et le type africanisé dans les zones subtropicales. Une étude approfondie a été réalisée en Chine et en Argentine dans le but d'identifier les virus présents, d'analyser leur distribution dans différentes zones climatiques et de réunir des informations sur les différentes espèces et sous-espèces d'abeilles présentes. Des abeilles mellifères adultes ont été collectées dans des ruchers des régions tempérées et subtropicales de Chine (zones peuplées exclusivement d'A. mellifera ou d'A. cerana et zones où A. mellifera et A. cerana coexistent) et d'Argentine (A. mellifera seulement). En Chine, six virus, à savoir le virus des ailes déformées, le virus des cellules royales noires, le virus du couvain sacciforme, le virus de la paralysie chronique de l'abeille, le virus de la paralysie aiguë de l'abeille et le virus israélien de la paralysie aiguë ont été détectés aussi bien chez A. cerana que chez A. mellifera ; en Argentine, quatre virus ont été détectés (virus des ailes déformées, virus des cellules royales noires, virus de la paralysie chronique de l'abeille et virus de la paralysie aiguë de l'abeille). Fait intéressant, les infections multiples étaient fréquentes en Chine, avec parfois jusqu'à cinq virus différents circulant dans certaines colonies sans provoquer de manifestations anormales apparentes. Aucun des échantillons analysés en Chine n'a été trouvé positif pour le virus de la paralysie lente de l'abeille. Les virus les plus fréquents étaient, en Chine, le virus des cellules royales noires et en Argentine, le virus des ailes déformées. Le virus du Cachemire n'a été trouvé dans aucun des échantillons analysés dans les deux pays.

Las abejas melíferas están amenazadas por diversos patógenos y parásitos. Se han descrito más de 18 virus que las afectan, muchos de los cuales se han detectado en China y la Argentina. En China se cultivan tanto Apis cerana como Apis mellifera, mientras que los apicultores argentinos crían diferentes ecotipos de A. mellifera: abejas europeas en las regiones templadas y subtropicales y abejas africanizadas en las zonas subtropicales. Los autores exponen un minucioso estudio realizado a la vez en China y la Argentina con el fin de analizar la actual presencia y distribución de virus en diferentes zonas climáticas y reunir información sobre distintas especies y subespecies de abeja. En primer lugar se recogieron abejas adultas de colmenares situados en regiones templadas y subtropicales de China (algunas donde hay exclusivamente poblaciones de A. mellifera, otras donde coexisten A. mellifera y A. cerana y otras zonas que albergan solo poblaciones de A. cerana) y la Argentina (solamente A. mellifera). En las poblaciones chinas tanto de A. cerana como de A. mellifera se detectaron seis virus: virus de las alas deformes (VAD); virus de las celdas reales negras (VCRN); virus de la cría ensacada (VCE); virus de la parálisis crónica de la abeja (VPCA); virus de la parálisis aguda de la abeja (VPAA); y virus de la variante israelí del virus de la parálisis aguda (VPAI), mientras que en la Argentina se observó la presencia de cuatro virus (VAD, VCRN, VPCA y VPAA). Un dato interesante es que en China se observaron con frecuencia infecciones múltiples, con hasta cinco virus diferentes circulando a la vez en algunas colonias sin que ello diera lugar a anormalidades aparentes. Ninguna de las muestras chinas analizadas en el estudio resultó positiva al virus de la parálisis lenta de la abeja. Los virus más prevalentes fueron el VCRN (China) y el VAD (Argentina). El virus Cachemira de las abejas estaba ausente de las muestras analizadas en ambos países.

Risk of intrauterine growth restriction among HIV-infected pregnant women: a cohort study.

The purpose of this investigation was to study the risk of intrauterine growth restriction in human immunodeficiency virus (HIV)-infected women and to describe the associated risk factors. A cohort study was performed among HIV-infected women who delivered in a single tertiary centre in Barcelona, Spain, from January 2006 to December 2011. Consecutive singleton pregnancies delivered beyond 22 weeks of pregnancy were included. Intrauterine growth restriction (IUGR) was defined as a birth weight below the 10th customised centile for gestational age and IUGR babies were compared to non-IUGR newborns. Intrauterine Doppler findings were described among IUGR foetuses. Baseline characteristics, HIV infection data and perinatal outcome were compared between groups. The results were adjusted for potential confounders. A total of 156 singleton pregnancies were included. IUGR occurred in 23.4 % of cases (38/156). In two-thirds of the cases detected before birth, Doppler abnormalities compatible with placental insufficiency were observed. IUGR pregnancies presented a worse perinatal outcome, mainly due to a higher risk of iatrogenic preterm delivery [adjusted odds ratio 6.9, 95 % confidence interval (CI) 1.4-33.5]. IUGR foetuses also had a higher risk of emergent Caesarean section and neonatal intensive care unit admission. No cases of intrauterine foetal death occurred. A high rate of IUGR was observed among HIV pregnancies, and it was associated with adverse perinatal outcomes, mainly iatrogenic preterm and very preterm birth due to placental insufficiency. Our results support that ultrasound detection and follow-up of IUGR foetuses should be part of routine antenatal care in this high-risk population to improve antenatal management.

Quantitative ultrasound texture analysis of fetal lungs to predict neonatal respiratory morbidity.

OBJECTIVE: To develop and evaluate the performance of a novel method for predicting neonatal respiratory morbidity based on quantitative analysis of the fetal lung by ultrasound. METHODS: More than 13,000 non-clinical images and 900 fetal lung images were used to develop a computerized method based on texture analysis and machine learning algorithms, trained to predict neonatal respiratory morbidity risk on fetal lung ultrasound images. The method, termed 'quantitative ultrasound fetal lung maturity analysis' (quantusFLM™), was then validated blindly in 144 neonates, delivered at 28 + 0 to 39 + 0 weeks' gestation. Lung ultrasound images in DICOM format were obtained within 48 h of delivery and the ability of the software to predict neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, was determined. RESULTS: Mean (SD) gestational age at delivery was 36 + 1 (3 + 3) weeks. Among the 144 neonates, there were 29 (20.1%) cases of neonatal respiratory morbidity. Quantitative texture analysis predicted neonatal respiratory morbidity with a sensitivity, specificity, positive predictive value and negative predictive value of 86.2%, 87.0%, 62.5% and 96.2%, respectively. CONCLUSIONS: Quantitative ultrasound fetal lung maturity analysis predicted neonatal respiratory morbidity with an accuracy comparable to that of current tests using amniotic fluid.

Intravenous ferrous sucrose versus placebo in addition to oral iron therapy for the treatment of severe postpartum anaemia: a randomised controlled trial.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of intravenous iron versus placebo added to standard oral iron therapy in the treatment of severe postpartum anaemia. DESIGN: A randomised, double-blind, parallel-group, placebo-controlled clinical trial was performed in a single centre. SETTING: Hospital Clinic of Barcelona, Barcelona, Spain. POPULATION: A cohort of 72 women with severe postpartum anaemia (6.0-8.0 g/dl) treated with oral ferrous sulphate (two tablets of 525 mg). METHODS: Women were randomised to receive either intravenous ferrous sucrose (200 mg/24 hours for two consecutive days) or intravenous placebo, in addition to standard iron therapy. Clinical and laboratory data were obtained at 1, 2, and 6 weeks. MAIN OUTCOME MEASURES: Haemoglobin and haematocrit at 1, 2, and 6 weeks. Other haematological and clinical parameters, psychological status, and adverse side effects were also evaluated. RESULTS: Haemoglobin and haematocrit values were comparable in women receiving intravenous iron or placebo in addition to oral iron therapy at any of the time points. At 6 weeks, haemoglobin level (mean ± SD) was 12.2 ± 1.0 versus 12.2 ± 0.9 g/dl, with a mean difference of -0.03 (95% CI -0.6 to 0.6), in the placebo and in the intravenous iron groups, respectively. No differences were found between clinical symptoms of anaemia, psychological status, and adverse side effects between groups. CONCLUSIONS: Intravenous iron added to oral iron therapy did not show significant benefits over placebo, neither in haemoglobin rise nor in symptoms or adverse side effects.

Randomised trial of cervical cerclage, with and without occlusion, for the prevention of preterm birth in women suspected for cervical insufficiency.

OBJECTIVE: To evaluate the effect of cerclage, with and without cervical occlusion. DESIGN: Multicentre, stratified, randomised controlled trial. SETTING: Hospital-based multicentre study with 18 tertiary centres from nine countries. POPULATION: Women with a history of cervical insufficiency (prophylactic trial) and women with a short cervix (therapeutic trial) were recruited from August 2006 to August 2011. METHODS: A centralised telephone randomisation service with a computer system was used to randomise women to cervical cerclage with or without cervical occlusion. Only the analyst performing the interim analyses was blinded. MAIN OUTCOME MEASURES: The take-home baby rate (number of infants discharged alive from the hospital), gestational age at delivery, and the number of days in the neonatal intensive care unit (NICU). RESULTS: Women (n = 309) were stratified into the prophylactic trial (n = 213) or the therapeutic trial (n = 96). The trial stopped early due to slow recruitment and an interim analysis showing no benefit of occlusion. Final analysis comprised 197 women in the prophylactic trial and 87 women in the therapeutic trial. No added effect of cervical occlusion was found in terms of the take-home baby rate in the prophylactic trial (92 versus 90%, RR 1.03, 95% CI 0.94-1.12) or in the therapeutic trial (81 versus 85%, RR 0.96, 95% CI 0.79-1.16). No effect of cervical occlusion was found in terms of gestational age at delivery and number of days the neonate spent in the NICU. Cervical occlusion was associated with no harm. CONCLUSIONS: Cervical occlusion with cerclage had no significant additional effect.

Acute and subchronic effects of ibuprofen on the ten spotted live-bearer fish Cnesterodon decemmaculatus (Jenyns, 1842).

Ibuprofen (IBP) is an anti-inflammatory drug found in aquatic environments, potentially toxic for the biota. We exposed the test fish C. decemmaculatus to two environmentally relevant concentrations (50 and 100 µg IBP/L) for 4 and 12 d and evaluated the effect on some biomarkers. Micronucleus test, nuclear abnormality test and comet assay indicated cyto-genotoxicity at both concentrations and exposure periods. Oxidative stress and biochemical biomarkers were not affected, excepting muscle AChE activity for 4 d. Muscle metabolic biomarkers showed significant decrease in ETS, lipid and protein content, while carbohydrate content was not affected. The CEA index increased at the lower IBP concentration for 4 and 12 d, possibly due to changes in body energy reserves. A full-factorial GLM performed to assess the effects of IBP and exposure times showed that the metabolic and genotoxicity biomarkers were the most sensitive to IBP toxicity, mainly at 50 µg IBP/L for 4 d.

Impact of exposure to arsenic on the bacterial microbiota associated with river biofilms in the Pampas region.

Freshwater contamination by arsenic (As) is a worldwide problem. It may be found in Pampean streams of Argentina at concentrations higher than those recommended by international organizations and stipulated by national regulations. Exposure to high As concentrations causes serious consequences to both human health and the environment. The general objective of this work was to evaluate the effect of As on the biofilm microbiota structure from Naveira stream, Luján, Province of Buenos Aires (Coordinates: 34º34'02″ S 59º03'51″ W). The biofilm collected was cultivated in glass aquaria at different As III concentrations (0, 0.2 and 20 mg / L), inside incubation chambers under controlled conditions (16 h light: 8 h dark and 24 ± 1 °C) and constant aeration for 31 d, with partial water renewal every 9 d. We amplified the hypervariable regions V3 and V4 of the bacterial 16S rRNA gene from biofilm bacterial community samples to determine the diversity and abundance of the different taxa. The taxonomic composition of each sample, the alpha diversity of each treatment and the main metabolic pathways were analyzed. Principal Component Analysis of the present phyla and a Linear Discriminant Analysis of the metabolic pathways was also performed. Significant changes were observed in relation to the taxonomic composition of the bacterial community after exposure to the metalloid. However, this effect was not observed at the low concentration used (0.2 mg / L), which is the one that corresponds to ecologically relevant levels. The significantly affected phyla were Verrucomicrobiota, Acidobacteriota, Patescibacteria, Hydrogenedentes and WPS-2. The relative abundances of the Verrucomicrobiota, WPS-2 and Patescibacteria groups were notably decreased in the treatment with high As, while the Acidobacteria group was increased in both treatments with As. The stream samples showed greater bacterial diversity than those grown in the laboratory without As. Finally, it was possible to characterize the metabolic profile of the biofilm developed under natural conditions in the leaves of the aquatic plant Elodea canadensis in the Naveira stream. In addition, results showed that biosynthesis-related pathways were more abundant at the high As concentration treatment (20 mg / L).

Evaluation of the Feasibility, Safety and Efficacy of the Use of Intravenous Infusions of Adenosine Triphosphate (ATP) in People Affected by Moderate to Severe Alzheimer's Disease: A Double-Blind Masked Clinical Trial for Dose Finding.

BACKGROUND: There are currently no drug therapies modifying the natural history of patients suffering Alzheimer's disease (AD). Most recent clinical trials in the field include only subjects in early stage of the disease, while patients with advanced AD are usually not represented. OBJECTIVES: To evaluate the feasibility, safety and efficacy of systemic infusions of adenosine triphosphate (ATP) in patients with moderate to severe AD, and to select the minimum effective dose of infusion. DESIGN: A phase IIb, randomized, double-blind, placebo-controlled clinical trial investigates. PARTICIPANTS: A total of 20 subjects with moderate or severe AD were included, 16 in the treatment group and 4 in the placebo group (4:1 randomization) at two dosage regimens, 6-hour or 24-hour infusions. RESULTS: The proof-of-concept study was successfully conducted, with no significant deviations from the study protocol and no serious adverse events reported. Regarding efficacy, only marginal differences were observed between ATP and placebo arms for H-MRS and MMSE variables. CONCLUSIONS: Our study demonstrates that the use of ATP infusion as therapy is feasible and safe. Larger studies are however needed to assess the efficacy of ATP in moderate to severe AD.

Cervical blood perfusion assessed using power Doppler-derived estimation of fractional moving blood volume: a reproducibility study.

OBJECTIVE: To evaluate the reproducibility of estimation of power Doppler-derived fractional moving blood volume (FMBV) in the uterine cervix of women with uncomplicated pregnancies. METHODS: Two experienced operators evaluated 30 uncomplicated singleton pregnancies at 20-24 weeks of gestation. The PDU box was positioned in a mid-sagittal view of the cervix, including the internal os and external os, in the same plane as that in which cervical length is measured. Two consecutive examinations were performed by each operator, in each of which the cervical length was measured and five consecutive good-quality images with PDU information were obtained. The region of interest (ROI) (cervix) was delineated offline and FMBV, which expresses the percentage of blood occupying the ROI, was calculated with purpose-designed software. Intra- and interobserver intraclass correlation coefficients (ICCs) and mean differences with 95% limits of agreement (LOA) were calculated. RESULTS: The median gestational age at examination was 22 + 0 weeks. Measurements (median ± SD) obtained for cervical length and FMBV were as follows: Operator A: 37 ± 7.4 mm and 8.11 ± 2.9%; Operator B: 37.5 ± 9.3 mm and 7.9 ± 3.3%, respectively. The intra- and interobserver ICCs for FMBV were 0.88 (95% CI, 0.75-0.94) and 0.82 (95% CI, 0.64-0.94), respectively. There was a mean difference in FMBV measurement between operators of - 0.2 ± 1.75% (95% LOA, - 3.7 to 3.2%). CONCLUSIONS: Reproducible assessment of cervical blood perfusion through estimation of FMBV can be achieved while cervical length is being measured.

Left ventricular inflow tract obstruction secondary to a myxoma in a dog.

This is the first description of a left ventricular inflow tract obstruction secondary to a myxoma in a dog. A 4 yr old, male fox terrier presented with a 1 mo history of cough and exercise intolerance. Expiratory dyspnea, pulmonary crackles, irregular cardiac rhythm, and a grade 4/6 pansystolic cardiac murmur over the left cardiac apex were the most important features on physical examination. The electrocardiogram revealed atrial fibrillation. Thoracic radiographs showed left-sided cardiac enlargement and mild pulmonary edema, especially in the hilar area. Two-dimensional transthoracic echocardiography showed severe left atrial dilation and a homogenous, echodense mass involving both leaflets of the mitral valve and the posteromedial papillary muscle, inducing mitral stenosis. Spectral Doppler echocardiography was consistent with severe left ventricular inflow tract obstruction secondary to a mass. Therapy for congestive heart failure was prescribed. Follow-up examinations of the dog 1 mo, 2 mo, and 6 mo after diagnosis showed an improvement in clinical signs, but similar echocardiographic features. Eleven months after diagnosis, the dog was euthanized at the owner's request because of recurrent congestive heart failure. The postmortem examination showed the cardiac tumor was consistent with a myxoma.