A multi-centre, open-label, prospective, observational study to assess the safety of a nifedipine oral solution in the treatment of preterm labor / Estudio multicéntrico, de diseño abierto, prospectivo y observacional para evaluar la seguridad de una solución oral de nifedipino en el tratamiento del parto prematuro

Objective: To analyze the safety profile of a nifedipine oral solution in the treatment of preterm labor (PTL). Methods: A multi-center, open-label, prospective, single-arm, observational study was conducted in 500 women with PTL to whom a nifedipine oral solution was prescribed according to its Summary of Product Characteristics. Safety profile and tolerability of oral administration of nifedipine solution during routine clinical practice was assessed as the primary objective of the study and treatment efficacy as secondary objective. Results: No severe adverse events were reported among these women, including severe hypotension. Eight patients (2.3%) reported adverse reactions of moderate intensity, and in 0.9% of the patients (3 cases), these adverse reactions caused the discontinuation of the treatment. Conclusions: The results of this study show that nifedipine oral solution exhibits an excellent safety profile used as a tocolytic treatment in women with PTL.(AU)

Objetivo: Analizar el perfil de seguridad de una solución oral de nifedipino en el tratamiento del parto prematuro (PP). Métodos: Se llevó a cabo un estudio observacional, prospectivo, de diseño abierto, de rama única y multicéntrico en 500 mujeres que presentaban un PP, a las que se les administró una solución oral de nifedipino según la ficha técnica del producto. El perfil de seguridad y la tolerancia de la solución oral de nifedipino, en el contexto de la práctica clínica rutinaria, fueron evaluados como objetivo primario del estudio, y la eficacia del tratamiento, como objetivo secundario. Resultados: No se notificaron efectos adversos graves, incluyendo hipotensión severa. Ocho pacientes (2,3%) presentaron reacciones adversas de intensidad moderada, y en el 0,9% de las pacientes (3 casos) estos efectos adversos provocaron la discontinuación del tratamiento. Conclusiones: Los resultados de este estudio muestran que la solución oral de nifedipino dispone de un excelente perfil de seguridad para su uso como tocolítico en el tratamiento de mujeres con PP.(AU)

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.

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.

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

La infección causada por el nuevo coronavirus SARS-CoV-2 (COVID-19) representa actualmente una de las mayores emergencias sanitarias a nivel mundial. La aparición de una nueva infección potencialmente grave y la situación de pandemia actual ha implicado importantes ajustes en la práctica clínica en medicina materno-fetal. Aunque no parece existir una mayor afectación o susceptibilidad al virus de las mujeres embarazadas respecto la población general, existen aspectos específicos ligados a la gestación que deben tenerse en cuenta de cara al diagnóstico y manejo de la COVID-19 en pacientes embarazadas. En el siguiente documento se exponen las recomendaciones y el protocolo de actuación ante la infección por COVID-19 durante el embarazo desarrollado en nuestro centro, basado en la evidencia científica disponible hasta la fecha y las principales recomendaciones internacionales

The severe acute respiratory syndrome coronavirus2 (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

Changes in Renal Resistive Index Values in Healthy Puppies during the First Months of Life.

The purpose of this study is to establish renal resistive index (RRI) of normal kidneys in puppies aged from newborn to 20 weeks of age and to determine the age at which RRI reaches adult dog values. Six healthy adult intact beagles and six puppies from 1 day after birth to 20 weeks of age were used. In the adult dogs, the ultrasonographic scans were performed once, and in the puppies, the ultrasonographic studies were performed on the first day after birth and at 1, 2, 3, 4, 6, 8, 12, 16, and 20 weeks of age. RRI was obtained at the interlobular and arcuate arteries in each kidney. There were no statistical differences between the RRI values obtained between the right and left kidney nor between intrarenal arteries (interlobar and arcuate). The RRI was the highest during the first weeks of life, after which it declined gradually with increasing age reaching adult dog values at 12 weeks of age. In conclusion, the normal mean RRI is age dependent in dogs. Twelve weeks can be regarded as the age at which adult mean RRI criteria can be applied to puppies.

[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.

Latencia al parto tras cerclaje de emergencia en gestación múltiple / Latency to delivery after emergency physical-examination indicated cerclage in twin pregnancy

Introducción: Las guías clínicas actuales recomiendan el uso del cerclaje de emergencia (CE) como tratamiento de la insuficiencia cervical con exposición de membranas en gestaciones únicas. Sin embargo, el CE en gestación múltiple es tema de controversia dado que no existen ensayos clínicos randomizados que demuestren su eficacia. Algunos estudios retrospectivos sugieren que el CE también podría prolongar la gestación en embarazos múltiples. El objetivo de nuestro estudio es evaluar los resultados de las gestaciones múltiples que se sometieron a un CE en nuestro centro. Materiales y métodos: Se diseñó un estudio retrospectivo que incluyó los CE realizados en gestaciones gemelares en nuestro centro entre 2007-2016. No fueron tributarias de CE gestaciones con malformaciones fetales, monocoriales-monoamnióticas, triple o superior y finalizaciones activas de la gestación. Variables primarias: latencia al parto espontáneo y edad gestacional al parto. Variables secundarias: mortalidad neonatal, ingreso en UCI neonatal, rotura prematura de membranas pretérmino, corioamnionitis y fallo del cerclaje. Resultados. El estudio incluyó 17 pacientes. La edad gestacional mediana (rango intercuartil) al parto fue de 27,1 (24,5-32,3) semanas y la latencia mediana (rango intercuartil) al parto fue de 43 (21-64) días. Hubo 4/17 (23,5%) casos de parto antes de las 24 semanas de gestación y 2/26 (7,7%) de muerte neonatal. Discusión: Estos resultados muestran que la latencia al parto después del CE en gestación múltiple es remarcable, por lo que podría ser considerado como una opción terapéutica. Sin embargo, se requiere evidencia basada en estudios randomizados para hacer una recomendación firme

Introduction: Current guidelines support the use of physical-examination indicated cerclage (PEIC) as a treatment for cervical insufficiency and membrane exposure in single pregnancies. However, PEIC in twin pregnancies is a controversial issue as no data from random clinical trial are available to demonstrate its efficacy. Few studies suggest that PEIC may prolong pregnancy also in twin pregnancies. The aim of this study was to evaluate the results of twin pregnancies that underwent a PEIC in our health centre. Material and methods: A retrospective review was performed on women that underwent a PEIC from 2007-2016 in our centre. Women were not eligible if they were carrying foetuses with major foetal anomalies, more than two foetuses or monochorionic-monoamniotic pregnancies, or three or more foetuses or requesting an elective termination of pregnancy. Primary outcomes: latency to spontaneous delivery and gestational age (GA) at delivery. Secondary outcomes: neonatal mortality and Neonatal Intensive Care Unit admission, preterm premature rupture of membranes (PPROM), chorioamnionitis and cerclage displacement. Results: The study included a total of 17 women. The median (inter-quartile range) gestational age at delivery was 27.1 (24.5-32.3) weeks, and median (inter-quartile range) latency, from cervical cerclage to delivery, was 43 (21-64) days. There were 4/17 (23.5%) cases of delivery before 24 weeks of pregnancy, and 2/26 (7.7%) cases of neonatal death. Discussion: These results suggest that latency to delivery after PEIC in twins is remarkable. Therefore, it could be considered as an optional management. Nevertheless, evidence based on random clinical trial is required to make firm recommendations on its formal use

Canine leishmaniasis associated with pericardial effusion in a 4-year-old dog.

A 4-year-old crossbreed dog presented with a two-day history of lethargy and abdominal effusion. Physical examination and echocardiography revealed pericardial effusion with cardiac tamponade. Pericardiocentesis was performed. Intracytoplasmic Leishmania amastigotes were found on cytological examination of the pericardial fluid. The animal was treated with N-methylglucamine antimoniate and allopurinol. After an initial favorable response, cardiac tamponade reoccurred one month later. The dog died during a pericardiectomy four months after the initial diagnosis. Histology confirmed the presence of chronic pericarditis. The presence of Leishmania amastigotes on cytological examination of pericardial effusion suggests a possible association between canine leishmaniasis and chronic pericarditis. This finding also supports the importance of cytological examination of pericardial fluid in areas endemic for canine leishmaniasis.

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.

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.

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.

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study.

BACKGROUND: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. OBJECTIVES: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. ANIMALS: Three hundred and fifty-four dogs with MMVD and cardiomegaly. MATERIALS AND METHODS: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. RESULTS: At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P < 0.0001, and LA:Ao -0.08 (IQR: -0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.

[Sleep apnoea-hypopnoea syndrome and narcolepsy. Description of a series of hospital patients]. / Sindrome de apneas-hipopneas y narcolepsia. Descripcion de una serie hospitalaria.

INTRODUCTION: Sleep disorders are highly prevalent among the general population, although very few cases of sleep apnoea-hypopnoea syndrome (SAHS) have been reported in patients with narcolepsy. This study reviews the sleep disorders found in patients with narcolepsy, the prevalence of SAHS associated with these patients and their response to the different treatments. PATIENTS AND METHODS: We conducted an observation-based retrospective descriptive analysis of 25 patients diagnosed with narcolepsy, who were treated in our centre between October 2012 and December 2016. RESULTS: Of 470 patients evaluated in the specialised neurology consultation unit, 25 patients were diagnosed with narcolepsy (5.31%); 65% were males and the remaining 35% were females; the mean age at the time of diagnosis was 40 years. 60% presented other associated sleep disorders, the most frequent being SAHS (36%). The efficacy rate of treatment with continuous positive airway pressure (CPAP) is 66% in patients with SAHS with an indication of CPAP. CONCLUSIONS: Altogether, 60% of patients with narcolepsy have a second associated sleep disorder (greater than the incidence of coexistence in the general population, of 20-25% of patients), and those reported are also the most frequent among the general population (SAHS, restless legs syndrome, periodic limb movement disorder). 36% of patients with narcolepsy have SAHS as an associated condition. Of these, 78% have reached a suitable degree of control over respiratory events; 57% have achieved control with CPAP, and the remaining 43% did not require CPAP for event correction with other methods.

TITLE: Sindrome de apneas-hipopneas y narcolepsia. Descripcion de una serie hospitalaria.Introduccion. Los trastornos del sueño son muy prevalentes en la poblacion general; sin embargo, la asociacion de sindrome de apneas-hipopneas (SAHS) en pacientes con narcolepsia se ha descrito en pocas ocasiones. Se revisan los trastornos del sueño encontrados en pacientes con narcolepsia, la prevalencia de SAHS asociado a estos pacientes y su respuesta a los tratamientos. Pacientes y metodos. Analisis descriptivo retrospectivo observacional de 25 pacientes, con diagnostico de narcolepsia, atendidos en nuestro centro desde octubre de 2012 hasta diciembre de 2016. Resultados. De 470 pacientes valorados en la consulta monografica de neurologia, hemos diagnosticado a 25 pacientes con narcolepsia (5,31%); el 65% eran hombres, y el 35%, mujeres. Edad media en el momento del diagnostico: 40 años. El 60% presenta otros trastornos del sueño asociados, el mas frecuente es el SAHS (36%). La eficacia del tratamiento con presion aerea positiva continua nasal (CPAP) es del 66% en los pacientes con SAHS con indicacion de CPAP. Conclusiones. El 60% de los pacientes con narcolepsia asocia un segundo trastorno del sueño (mayor que la incidencia de coexistencia en la poblacion general, del 20-25% de los pacientes), y los descritos tambien son los mas frecuentes en la poblacion general (SAHS, sindrome de piernas inquietas, movimientos periodicos de las piernas). El 36% de los pacientes con narcolepsia asocia SAHS. De ellos, en el 78% se ha conseguido un control de eventos respiratorios adecuado; el 57% se ha controlado con CPAP y el 43% restante no ha precisado CPAP por correccion de eventos con otros metodos.

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.

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,。.

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial.

BACKGROUND: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. HYPOTHESIS/OBJECTIVES: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. ANIMALS: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5. METHODS: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. RESULTS: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.