Impact of COVID-19 disease on placental histopathology. PLAXAVID study.

BACKGROUND: The impact of COVID-19 on pregnancy has been analyzed suggesting an increased risk of placental lesions that might lead to maternal and neonatal complications. However, the current published evidence is not conclusive because contradictory results. METHODS: PLAXAVID is an observational, retrospective, histopathological, single-center study that aimed to evaluate the prevalence of vascular and inflammatory lesions in placental and umbilical cord samples of one hundred women infected by SARS-CoV-2 during pregnancy. RESULTS: The histopathological analysis showed that in most of the placentas (77.8%) there were signs of maternal vascular malperfusion (MVM; primary endpoint). The most common MVM features were an accelerated villous maturation (37.4%), central villous infarcts (33.3%), and villous agglutination (46.5%). Fetal vascular malperfusion (FVM) was identified in 57.6% of samples, and the most frequent features were hyalinized avascular villi (38.4%), fetal vascular thrombi (20.2%) and umbilical cord at risk of partial obstruction (14.1%). Acute and chronic inflammatory pathology were noticed in 22.2% and 49.5% of placentas, respectively. No significant correlations were found between MVM presence and the time, duration, and severity of infection, nor with the duration of pregnancy. However, in critically ill patients, the pregnancy duration (p=0.008), newborn weight (p=0.003), and APGAR test scores (p<0.001) were significantly lower. The same trend was observed considering the presence of infection at the time of delivery and in preterm births. CONCLUSION: A very high percentage of placentas with vascular and/or inflammatory lesions was found in the analyzed cohort. Therefore, PLAXAVID study results supported that COVID-19 should be considered a risk factor during gestation and requires close monitoring of pregnancy.

¿Es el estiramiento pasivo del cuádriceps igual de efectivo que el autoestiramiento en jugadores de fútbol? Ensayo clínico aleatorizado / Is quadriceps passive stretching as effective as self-stretching in soccer athletes? Randomized clinical trial

Objetivo Comparar los efectos de un estiramiento pasivo del músculo cuádriceps frente a un autoestiramiento en la flexibilidad de los músculos del muslo y el rango de movimiento (ROM) de la cadera en jugadores de fútbol. Métodos Se diseñó un ensayo clínico aleatorizado en el que se incluyeron 34 jugadores de fútbol amateur con déficit de flexibilidad en el músculo cuádriceps. Los jugadores fueron aleatorizados en dos grupos (grupo estiramiento o grupo autoestiramiento). Cada participante recibió una única sesión de estiramiento pasivo o autoestiramiento del cuádriceps en su pierna dominante. Se valoró la flexibilidad del cuádriceps mediante el test de Ely, la flexibilidad de los isquiotibiales mediante el Passive Knee Extension test, y ROM de flexión y extensión de la cadera. Resultados Ambos grupos mostraron un aumento estadísticamente significativo de la flexibilidad del cuádriceps, de la flexibilidad de los isquiotibiales y del ROM de extensión de la cadera sin diferencias significativas entre ellos (p>0,05). El grupo estiramiento mostró unos tamaños del efecto grandes en la flexibilidad y el ROM de extensión (d>0,8), siendo superiores a los registrados en el grupo autoestiramiento. Conclusiones La flexibilidad de los músculos cuádriceps e isquiotibiales, así como el ROM de extensión de cadera aumentaron tras el estiramiento y el autoestiramiento del músculo cuádriceps. Los tamaños del efecto mostrados por el grupo estiramiento fueron superiores a los del grupo autoestiramiento (AU)

Objective To compare the effects of quadriceps passive stretching or quadriceps self-stretching in muscle flexibility and hip range of motion (ROM) in football athletes. Methods A randomized clinical trial was carried out. Thirty-four football athletes with lack of flexibility in the quadriceps muscle were included and randomized in two groups (Stretching group or self-stretching group) and received a single session of quadriceps passive stretching or quadriceps self-stretching in the dominant lower limb. The outcome variables were: quadriceps flexibility measured with the Ely's test, hamstring flexibility measured with the Passive Knee Extension test and hip flexion and extension ROM. Results Both groups achieved a statistically significant improvement of quadriceps flexibility, hamstrings flexibility and hip extension ROM without statistically significant differences between them (p>0.05). The stretching group reported large effect sizes in muscle flexibility and hip extension ROM (d>0.8), and the effect sizes of the stretching group were higher than the self-stretching group. Conclusions Flexibility of the quadriceps and hamstring muscles as well as hip extension ROM increased after stretching and self-stretching of the quadriceps muscle. The effect sizes shown by the stretching group were higher than those of the self-stretching group (AU)

Diagnostic accuracy of first-trimester combined screening for early-onset and preterm pre-eclampsia at 8-10 compared with 11-13 weeks' gestation.

OBJECTIVES: To compare the ability of first-trimester combined screening for pre-eclampsia (PE) to predict early-onset and preterm PE when pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) were assessed before vs after 11 weeks' gestation. METHODS: This was a secondary analysis of a prospective cohort study of singleton pregnancies undergoing routine first-trimester screening conducted at Vall d'Hebron University Hospital, Barcelona, Spain, between October 2015 and September 2017. Demographic characteristics, obstetric history, maternal history and biophysical markers (mean uterine artery pulsatility index and mean arterial blood pressure (MAP)) were recorded at the first-trimester scan (at 11 + 0 to 13 + 6 weeks' gestation). Maternal serum concentrations of PAPP-A and PlGF were assessed from the routine first-trimester blood test (at 8 + 0 to 13 + 6 weeks). Women were classified into two groups depending on whether serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks or at 11 + 0 to 13 + 6 weeks. Probability scores for early-onset and preterm PE were calculated by using two different algorithms: the multivariate Gaussian-distribution model and The Fetal Medicine Foundation (FMF) competing-risks model. Receiver-operating-characteristics (ROC) curves were produced and detection rates at fixed 5% and 10% false-positive rates were computed to compare the performance of these algorithms when PAPP-A and PlGF were assessed before vs after 11 weeks. RESULTS: Of the 2641 women included, serum biomarkers were assessed before 11 weeks in 1675 (63.4%) and at or after 11 weeks in 966 (36.6%). Of these, 90 (3.4%) women developed PE, including 11 (0.4%) cases of early-onset PE and 30 (1.1%) of preterm PE. Five (45.5%) cases of early-onset and 16 (53.3%) of preterm PE were identified in the group in which serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks and six (54.5%) cases of early-onset and 14 (46.7%) of preterm PE in the group in which serum biomarkers were assessed at 11 + 0 to 13 + 6 weeks. In the prediction of early-onset and preterm PE using the Gaussian algorithm, no differences were observed between the areas under the ROC curves (AUCs) when PAPP-A and PlGF were measured before or after 11 weeks. In the prediction of early-onset and preterm PE using the FMF algorithm, no differences were observed between AUCs for any of the combinations used for risk calculation when the serum biomarkers were obtained before vs after 11 weeks, except for the combination of PAPP-A and MAP, which showed a greater AUC for the prediction of early-onset PE when PAPP-A was measured at or after 11 weeks. CONCLUSIONS: The prediction of early-onset and preterm PE is similar when serum biomarkers are measured before or after 11 weeks. This allows the use of a two-step approach for PE risk assessment that permits immediate risk calculation at the time of the first-trimester scan. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Pre-eclampsia-like syndrome induced by severe COVID-19: a prospective observational study.

OBJECTIVES: To investigate the incidence of clinical, ultrasonographic and biochemical findings related to pre-eclampsia (PE) in pregnancies with COVID-19, and to assess their accuracy to differentiate between PE and the PE-like features associated with COVID-19. DESIGN: A prospective, observational study. SETTING: Tertiary referral hospital. PARTICIPANTS: Singleton pregnancies with COVID-19 at >20+0  weeks. METHODS: Forty-two consecutive pregnancies were recruited and classified into two groups: severe and non-severe COVID-19, according to the occurrence of severe pneumonia. Uterine artery pulsatility index (UtAPI) and angiogenic factors (soluble fms-like tyrosine kinase-1/placental growth factor [sFlt-1/PlGF]) were assessed in women with suspected PE. MAIN OUTCOME MEASURES: Incidence of signs and symptoms related to PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, abnormal UtAPI and increased sFlt-1/PlGF. RESULTS: Thirty-four cases were classified as non-severe and 8 as severe COVID-19. Five (11.9%) women presented signs and symptoms of PE, all five being among the severe COVID-19 cases (62.5%). However, abnormal sFlt-1/PlGF and UtAPI could only be demonstrated in one case. One case remained pregnant after recovery from severe pneumonia and had a spontaneous resolution of the PE-like syndrome. CONCLUSIONS: Pregnant women with severe COVID-19 can develop a PE-like syndrome that might be distinguished from actual PE by sFlt-1/PlGF, LDH and UtAPI assessment. Healthcare providers should be aware of its existence and monitor pregnancies with suspected pre-eclampsia with caution. TWEETABLE ABSTRACT: This study shows that a pre-eclampsia-like syndrome could be present in some pregnancies with severe COVID-19.

Pregnancy outcomes after maternal Zika virus infection in a non-endemic region: prospective cohort study.

OBJECTIVES: The aim was to describe pregnancy outcomes after Zika virus (ZIKV) infection in a non-endemic region. METHODS: According to the Spanish protocol issued after the ZIKV outbreak in Brazil in 2015, all pregnant women who had travelled to high-burden countries were screened for ZIKV. Serological and molecular tests were used to identify ZIKV-infected pregnant women. They were classified as confirmed ZIKV infection when reverse transcription (RT) PCR tested positive, or probable ZIKV infection when ZIKV immunoglobulin M and/or immunoglobulin G and ZIKV plaque reduction neutralization tests were positive. Women found positive using molecular or serological tests were prospectively followed-up with ultrasound scans and neurosonograms on a monthly basis until delivery; magnetic resonance imaging and amniotic fluid testing were performed after signed informed consent. Samples of placenta, and fetal and neonatal tissues were obtained. RESULTS: Seventy-two pregnant women tested positive for ZIKV infection: ten were confirmed by RT-PCR, and 62 were probable cases based on serological tests. The prevalence of adverse perinatal outcomes was 33.3% (three out of nine, 95% CI 12.1-64.6%): two cases of congenital ZIKV syndrome (CZS) and one miscarriage, all born to women infected in the first trimester of gestation. All ZIKV-confirmed women had persistent viraemias beyond 2 weeks (median 61.50 days; IQR 35.50-80.75). Amniotic fluid testing was only positive in the two fetuses with anomalies. CONCLUSION: The prevalence of perinatal adverse outcomes for women with ZIKV-confirmed infection was 33.3%. Amniocentesis for ZIKV RT-PCR is recommended when fetal abnormalities are found. Intensive prenatal and postnatal follow-up of ZIKV-infected pregnancies is advised in confirmed cases.

In utero negativization of Zika virus in a foetus with serious central nervous system abnormalities.

We describe a case of a pregnant woman with Zika virus (ZIKV) infection and a foetus with severe brain malformations. ZIKV tested positive in amniotic fluid at 19 weeks but was negative at delivery. The newborn did not meet the case definition of congenital ZIKV syndrome because neither ZIKV RNA nor IgM antibodies were detected; however, prenatal brain lesions were confirmed after birth (Graphical Abstract).

Enfermedad grasa del hígado no alcohólica. Desde la resistencia a la insulina a la disfunción mitocondrial / Non-alcoholic fatty liver disease. From insulin resistance to mitochondrial dysfunction

La enfermedad grasa del hígado no alcohólica representa unconjunto de lesiones hepáticas similares a las que produce el alcoholque se aparecen en personas que no consumen alcohol de formaabusiva. Cuando las lesiones consisten en degeneración grasae hidrópica, inflamación y, eventualmente, fibrosis se habla de esteatohepatitisno alcohólica (EHNA). No se conoce con exactitudla patogenia de estas lesiones, pero en la mayoría de los casos seasocian a la resistencia a la insulina. Consecuencia de esta, se producela lipólisis del tejido adiposo abdominal y la llegada excesivade ácidos grasos al hígado. Esto, junto con un trastorno para laexportación de los triglicéridos en forma de VLDL, determina laformación de un hígado graso. El componente inflamatorio y degenerativohepatocelular de la EHNA se atribuye al estrés oxidativo.En la génesis de este interviene la pérdida de actividad de lacadena respiratoria mitocondrial. Esto puede ser originado por elTNF-alfa, la inducción de la iNOS, la formación de peroxinitrito y lanitración en tirosina de las enzimas de esa cadena. Consecuenciasdel estrés oxidativo son: peroxidación de los lípidos de las membranascelulares, activación de las células estrelladas del hígado, fibrosishepática, inflamación crónica y apoptosis

Non-alcoholic fatty liver disease represents a set of liver lesionssimilar to those induced by alcohol that develop in individuals withno alcohol abuse. When lesions consist of fatty and hydropic degeneration,inflammation, and eventually fibrosis, the condition isdesignated non-alcoholic steatohepatitis (NASH). The pathogenesisof these lesions is not clearly understood, but they are associatedwith insulin resistance in most cases. As a result, abdominal fattissue lipolysis and excessive fatty acid uptake by the liver occur.This, together with a disturbance of triglyceride export as VLDL,results in fatty liver development. Both the inflammatory and hepatocellulardegenerative components of NASH are attributed tooxidative stress. Mitochondrial respiratory chain loss of activityplays a critical role in the genesis of latter stress. This may be initiatedby an increase in the hepatic TNF-alpha, iNOS induction, peroxynitriteformation, tyrosine nitration and inactivation of enzymesmaking up this chain. Consequences of oxidative stress include:lipid peroxidation in cell membranes, stellate cell activation in theliver, liver fibrosis, chronic inflammation, and apoptosis

Non-alcoholic fatty liver disease. From insulin resistance to mitochondrial dysfunction.

Non-alcoholic fatty liver disease represents a set of liver lesions similar to those induced by alcohol that develop in individuals with no alcohol abuse. When lesions consist of fatty and hydropic degeneration, inflammation, and eventually fibrosis, the condition is designated non-alcoholic steatohepatitis (NASH). The pathogenesis of these lesions is not clearly understood, but they are associated with insulin resistance in most cases. As a result, abdominal fat tissue lipolysis and excessive fatty acid uptake by the liver occur. This, together with a disturbance of triglyceride export as VLDL, results in fatty liver development. Both the inflammatory and hepatocellular degenerative components of NASH are attributed to oxidative stress. Mitochondrial respiratory chain loss of activity plays a critical role in the genesis of latter stress. This may be initiated by an increase in the hepatic TNFalpha, iNOS induction, peroxynitrite formation, tyrosine nitration and inactivation of enzymes making up this chain. Consequences of oxidative stress include: lipid peroxidation in cell membranes, stellate cell activation in the liver, liver fibrosis, chronic inflammation, and apoptosis.

IL-6 y remodelación de la matriz extracelular / IL-6 and extracellular matrix remodeling

No disponible

[Hypertensive patients treated in Spain, 1990-1993]. / Estudio sobre los enfermos hipertensos en tratamiento en España durante el período 1990-1993.

BACKGROUND: The main goal of our work was to gain knowledge from the pharmaco-epidemiological perspective on the use of anti-hypertensive drugs in our country, in order to obtain a rough estimation of the number of hypertensive patients under treatment in various Autonomous Communities. METHODS: The data regarding the consumption of hypertensive drugs (mono-medicines) from 1990 to 1993 have been obtained from the Vice-Directorate General for Treatment and Pharmaceutical Planning. The methodology used to calculate the "Estimated Prevalence Patient-day" under treatment with these drugs is based on the WHO recommendations for the Studies on the use of Medicines. Estimated Prevalence of Patient-day (EPPD) has been calculated by using the Defined Daily Dosage of each anti-hypertensive drug. RESULTS: The number of hypertensive patients under treatment with these drugs was 1.763.937, 1.966.396, 2.226.225 and 2.435.294, from 1990 to 1993, respectively. At the end of our study, in 1993, the number of hypertensive patients under treatment in Spain is nearly 50% of the total number of hypertensive patients. There are some differences amongst regions; thus, the Autonomous Communities of Aragón, Castilla-La Mancha, Cataluña, País Valenciano and Murcia are noticeable as regions where the number of hypertensive patients treated exceeds the national average. CONCLUSIONS: The number of hypertensive patients under treatment has considerably increased between 1990 to 1993 (+ 40%). An increase is observed in the number of hypertensive patients treated with calcium antagonists and ECA inhibitors and a decrease is observed in the proportion of hypertensive patients under treatment with Beta-blockers and diuretics.