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Fetal hydrops as detected by prenatal ultrasound usually carries a poor prognosis depending on the underlying aetiology. We describe the prenatal and postnatal clinical course of two unrelated female probands in whom de novo heterozygous missense variants in the planar cell polarity gene CELSR1 were detected using exome sequencing. Using several in vitro assays, we show that the CELSR1 p.(Cys1318Tyr) variant disrupted the subcellular localisation, affected cell-cell junction, impaired planar cell polarity signalling and lowered proliferation rate. These observations suggest that deleterious rare CELSR1 variants could be a possible cause of fetal hydrops.
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Heterocigoto , Hidropesía Fetal , Mutación Missense , Humanos , Femenino , Mutación Missense/genética , Hidropesía Fetal/genética , Hidropesía Fetal/patología , Embarazo , Derrame Pleural/genética , Derrame Pleural/patología , Cadherinas/genética , Secuenciación del Exoma , Polaridad Celular/genéticaRESUMEN
Purpose The measurement of fetal cardiovascular function parameters is not yet established in prenatal diagnostics. Now that the research field of fetal programming is becoming increasingly important, this might change. Fetal cardiovascular changes have been described above all in early/severe fetal growth restriction (FGR). The aim of this study was to investigate functional echocardiographic parameters in fetuses with late-onset small for gestational age (SGA)/FGR. Materials and methods A prospective cohort of SGA fetuses (including FGR) and a control group with similar distribution of gestational age were studied. Parameters of systolic, diastolic and global cardiac function, morphometry and measurements of the fetal abdominal aorta were collected. Results A total of 149 SGA fetuses and 143 control fetuses were included from 32 weeks until term. The total SGA group was further divided into SGA 3rd-10th (fetuses between the 3rd and 10th weight percentile) and FGR subgroups. In the total SGA group, relative right and left ventricular wall thickness, left E/A ratio, isovolumetric contraction time and left myocardial performance index were significantly increased compared to controls after adjustment for gestational age. MAPSE, TAPSE, ejection time, left cardiac output and abdominal aortic distensibility were significantly lower. The changes were more pronounced in the FGR subgroup. Conclusion Even in a group of late-onset SGA/FGR situation, echocardiographic parameters are already altered in utero. Zusammenfassung Ziel Die Messung fetaler kardiovaskulärer Funktionsparameter ist in der Pränataldiagnostik noch nicht etabliert. Nachdem das Forschungsgebiet der fetalen Programmierung einen immer höheren Stellenwert hat, könnte sich das bald ändern. Vor allem bei früher fetaler Wachstumsrestriktion (FGR) sind kardiovaskuläre Veränderungen beschrieben. Ziel dieser Studie war es dies bei Feten mit spät einsetzender FGR zu untersuchen. Material und Methode Eine prospektive Kohorte von Feten, die zu klein für das Gestationsalter (SGA) sind (einschließlich FGR) sowie eine Kontrollgruppe ähnlichen Gestionsalters wurden untersucht. Es wurden Parameter der systolischen, diastolischen sowie globalen Herzfunktion, der Morphometrie sowie Messungen der fetalen Aorta abdominalis erhoben. Ergebnisse Insgesamt wurden 149 SGA Feten sowie 143 Kontrollfeten ab 32 Schwangerschaftswochen eingeschlossen. Die Gesamt-SGA Gruppe wurde für eine Subgruppenanalyse weiterhin in eine SGA (SGA 3-10: Feten zwischen der 3. und 10. Gewichtsperzentile) sowie eine FGR Subgruppe unterteilt. In der Gesamt-SGA Gruppe zeigten sich im Vergleich zu den Kontrollen nach Adjustierung an das Gestationsalter die relative rechte sowie linke Ventrikelwanddicke, das linke E/A-Verhältnis, die isovolumetrische Kontraktionszeit und der linke myokardiale Performanceindex signifikant erhöht. MAPSE, TAPSE, die Ejektionszeit, das linke Herzzeitvolumen und die Beweglichkeit der Aorta abdominalis waren signifikant geringer. Die Ergebnisse waren im Subgruppenvergleich in der FGR Subgruppe ausgeprägter. Schlussfolgerung Auch in einer Gruppe spät einsetzender SGA/FGR Situation sind echokardiographische Parameter bereits intrauterin verändert.
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This study aimed to evaluate the in silico and in vitro inhibitory effect of the combined use of galantamine (GAL) and donepezil (DON) against acetylcholinesterase and butyrylcholinesterase (BuChE) enzymes. In silico and in vitro cholinesterase analysis were carried out for GAL and DON alone and combined. Molecular modeling studies were carried out (docking analysis, molecular dynamics simulation, and quantum theory of atoms in molecules). Cholinesterase's inhibitory activities by modified Ellman's method and the drug combination effect using the Chou-Talalay method were assayed. GAL/DON combination showed the co-occupancy of the ligands in both enzymes through in silico studies. Regarding in vitro BuChE inhibition analyses, three of five combinations showed an interaction between GAL and DON at the threshold of additive affect (0.9 < CI < 1.1), with a tendency toward a synergistic effect for higher concentrations. This is the first report showing the efficacy of the GAL/DON combinations inhibiting BuChE, showing the importance of analyzing the behavior of different ligands when co-occupancy into the active site is possible. These combinations might be a possible therapy to improved efficacy, reduced doses, minor side effects, and high levels of the neurotransmitter in the synaptic space for Alzheimer's disease.
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Enfermedad de Alzheimer , Galantamina , Humanos , Galantamina/farmacología , Butirilcolinesterasa/metabolismo , Donepezilo/farmacología , Inhibidores de la Colinesterasa/farmacología , Acetilcolinesterasa/metabolismo , Relación Estructura-Actividad , Enfermedad de Alzheimer/tratamiento farmacológico , Simulación del Acoplamiento MolecularRESUMEN
Metallo-phthalocyanines (MPc) are common photosensitizers with ideal photophysical and photochemical properties. Also, these molecules have shown to interact with non-canonical nucleic acid structures, such as G-quadruplexes, and modulate oncogenic expression in cancer cells. Herein, we report the synthesis and characterisation of two metallo-phthalocyanines containing either zinc (ZnPc) or nickel (NiPc) in the central aromatic core and four alkyl ammonium lateral chains. The interaction of both molecules with G-quadruplex DNA was assessed by UV-Vis, fluorescence and FRET melting experiments. Both molecules bind strongly to G-quadruplexes and stabilise these structures, being NiPc the most notable G-quadruplex stabiliser. In addition, the photosensitizing ability of both metal complexes was explored by the evaluation of the singlet oxygen generation and their photoactivation in cells. Only ZnPc showed a high singlet oxygen generation either by direct observation or by indirect evaluation using a DPBF dye. The cellular evaluation showed mainly cytoplasmic localization of ZnPc and a decrease of the IC50 values of the cell viability of ZnPc upon light activation of two orders of magnitude. Two metallo-phthalocyanines containing zinc and nickel within the aromatic core have been investigated as G-quadruplex stabilizers and photosensitizers. NiPc shows a high G4 binding but negligible photosensitizing ability while ZnPc exhibits a moderate binding to G-quadruplex together with a high potency to generate singlet oxygen and photocytotoxicity. The interaction with G4s and capacity to be photosensitized is associated with the geometry adopted by the central metal core of the phthalocyanine scaffold.
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Antineoplásicos , G-Cuádruplex , Compuestos Organometálicos , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Oxígeno Singlete/química , Níquel , Antineoplásicos/química , Compuestos Organometálicos/química , Zinc/química , Compuestos de ZincRESUMEN
PURPOSE: To evaluate the relationship between cerebroplacental ratio (CPR) and the need for operative delivery due to intrapartum fetal compromise (IFC) and adverse perinatal outcome (APO) in appropriate-for-gestational-age (AGA) late-term pregnancies undergoing induction of labor. The predictive performance of CPR was also assessed. MATERIALS AND METHODS: Retrospective study including singleton AGA pregnancies that underwent elective induction of labor between 41â+â0 and 41â+â6 weeks and were delivered before 42â+â0 weeks. IFC was defined as persistent pathological CTG or pathological CTG and fetal scalp pH <â7.20. Operative delivery included instrumental vaginal delivery (IVD) and cesarean section (CS). APO was defined as a composite of umbilical artery pH <â7.20, Apgar score <â7âat 5 minutes, and admission to the neonatal intensive care unit for >â24 hours. RESULTS: The study included 314 women with 32 (10â%) IVDs and 49 (16â%) CSs due to IFC and 85 (27â%) APO cases. Fetuses with CPR <â10th percentile showed a significantly higher rate of operative delivery for IFC (40â% (21/52) vs. 23â% (60/262); pâ=â0.008) yet not a significantly higher rate of APO (31â% (16/52) vs. 26â% (69/262); pâ=â0.511). The predictive values of CPR for operative delivery due to IFC and APO showed sensitivities of 26â% and 19â%, specificities of 87â% and 84â%, positive LRs of 2.0 and 1.2, and negative LRs of 0.85 and 0.96, respectively. CONCLUSION: Low CPR in AGA late-term pregnancies undergoing elective induction of labor was associated with a higher risk of operative delivery for IFC without increasing the APO rate. However, the predictive value of CPR was poor.
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Cesárea , Resultado del Embarazo , Recién Nacido , Embarazo , Femenino , Humanos , Pronóstico , Estudios Retrospectivos , Sufrimiento Fetal , Estudios Prospectivos , Feto , Arterias Umbilicales/diagnóstico por imagen , Ultrasonografía Prenatal , Flujo Pulsátil , Trabajo de Parto InducidoRESUMEN
PURPOSE: To describe the perinatal outcome of a prospective cohort of late-onset small-for-gestational-age (SGA) fetuses and to test adverse perinatal outcome (APO) prediction using Doppler measurements. METHODS: Singleton pregnancies from 32 weeks with suspicion of SGA (followed-up each 2 weeks) and randomly selected healthy controls at a university hospital were included. The whole SGA group was divided into the FGR subgroup or SGA percentile 3-10 subgroup.âThe following Doppler measurements were evaluated prospectively: umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, cerebro-placental ratio (CPR), and mean uterine artery (mUtA) PI. APO was defined as arterial cord blood pH ≤â7.15 and/or 5-minute Apgar ≤â7 and/or emergency operative delivery and/or admission to the neonatal unit. Induction of labor was indicated according to a stage-based protocol. RESULTS: A total of 149 SGA and 143 control fetuses were included. The number of operative deliveries was similar between both groups (control: 29â%, SGA: 28â%), especially the cesarean delivery rate after the onset of labor (11â% vs. 10â%). Most SGA cases ended up in induction of labor (61â% vs. 31â%, pâ<â0.001). The areas under the curve (AUC) for APO prediction were similar using the last UA PI, MCA PI, CPR, and mUtA PI and barely reached 0.60. The AUC was best for the FGR subgroup, using the minimal CPR or maximum mUtA PI z-score of all longitudinal measurements (AUCâ=â0.63). CONCLUSION: SGA fetuses do not have a higher rate of operative delivery if managed according to a risk stratification protocol. Prediction of APO is best for SGA and FGR using the "worst" CPR or mUtA PI but it remains moderate.
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Enfermedades del Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Femenino , Humanos , Recién Nacido , Embarazo , Retardo del Crecimiento Fetal/diagnóstico por imagen , Feto/diagnóstico por imagen , Estudios de Seguimiento , Edad Gestacional , Placenta , Tercer Trimestre del Embarazo , Estudios Prospectivos , Ultrasonografía Doppler/métodos , Ultrasonografía Prenatal/métodos , Arterias Umbilicales/diagnóstico por imagen , Estudios de Casos y ControlesRESUMEN
Rhabdoid meningiomas (RM) shows heterogeneous histological findings, and a wide variety of chromosomal copy number alterations (CNA) are associated with an unpredictable course of the disease. In this study, we analyzed a series of 305 RM samples from patients previously reported in the literature and 33 samples from 23 patients studied in our laboratory. Monosomy 22-involving the minimal but most common recurrent region loss of the 22q11.23 chromosomal region was the most observed chromosomal alteration, followed by losses of chromosomes 14, 1, 6, and 19, polysomies of chromosomes 17, 1q, and 20, and gains of 13q14.2, 10p13, and 21q21.2 chromosomal regions. Based on their CNA profile, RM could be classified into two genetic subgroups with distinct clinicopathologic features characterized by the presence of (1) chromosomal losses only and (2) combined losses and gains of several chromosomes. The latter displays a higher frequency of WHO grade 3 tumors and poorer clinical outcomes.
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Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/genética , Meningioma/patología , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patología , Aberraciones Cromosómicas , MonosomíaRESUMEN
Early kinetics of SARS-CoV-2 viral load (VL) in plasma determined by quantitative reverse-transcription polymerase chain reaction (RT-PCR) was evaluated as a predictor of poor clinical outcome in a prospective study and assessed in a retrospective validation cohort. Prospective observational single-center study including consecutive adult patients hospitalized with COVID-19 between November 2020 and January 2021. Serial plasma samples were obtained until discharge. Quantitative RT-PCR was performed to assess SARS-CoV-2 VL. The main outcomes were in-hospital mortality, admission to the Intensive Care Unit (ICU), and their combination (Poor Outcome). Relevant viremia (RV), established in the prospective study, was assessed in a retrospective cohort including hospitalized COVID-19 patients from April 2021 to May 2022, in which plasma samples were collected according to clinical criteria. Prospective cohort: 57 patients were included. RV was defined as at least a twofold increase in VL within ≤2 days or a VL > 300 copies/ml, in the first week. Patients with RV (N = 14; 24.6%) were more likely to die than those without RV (35.7% vs. 0%), needed ICU admission (57% vs. 0%) or had Poor Outcome (71.4% vs. 0%), (p < 0.001 for the three variables). Retrospective cohort: 326 patients were included, 18.7% presented RV. Patients with RV compared with patients without RV had higher rates of ICU-admission (odds ratio [OR]: 5.6 [95% confidence interval [CI]: 2.1-15.1); p = 0.001), mortality (OR: 13.5 [95% CI: 6.3-28.7]; p < 0.0001) and Poor Outcome (OR: 11.2 [95% CI: 5.8-22]; p < 0.0001). Relevant SARS-CoV-2 viremia in the first week of hospitalization was associated with higher in-hospital mortality, ICU admission, and Poor Outcome. Findings observed in the prospective cohort were confirmed in a larger validation cohort.
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COVID-19 , Adulto , COVID-19/diagnóstico , Hospitalización , Humanos , Estudios Prospectivos , Estudios Retrospectivos , SARS-CoV-2 , ViremiaRESUMEN
OBJECTIVES: An association between fetal growth restriction (FGR) and increased predisposition to cardiovascular disease (CVD) is suggested. The aim of this study was to evaluate subclinical signs of fetal cardiac remodeling in late-onset small-for-gestational-age (SGA) and growth-restricted fetuses using two-dimensional speckle tracking echocardiography (2D-STE). METHODS: This is a prospective cohort study, including 117 late-onset (≥32 weeks) SGA (birthweight≤10th centile) fetuses and 102 gestational age matched controls. A subgroup analysis was performed: FGR was defined based on either BW (
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Ecocardiografía/métodos , Corazón Fetal/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Ultrasonografía Prenatal , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Retardo del Crecimiento Fetal , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , EmbarazoRESUMEN
OBJECTIVE: Late-onset small-for-gestational-age (SGA) fetuses usually show normal uterine artery Doppler and were long considered to have a good peri- and postnatal outcome. Recently, these fetuses were identified to have a risk factor for cardiovascular disease. The aim of our study was to evaluate former SGA children concerning their cardiovascular risk and nutrition behavior at the age of 1 year. METHODS: We performed a prospective longitudinal cohort study at the University Hospital "Klinikum rechts der Isar" of the Technical University of Munich. Singleton pregnancies from 32 weeks with suspicion of SGA and healthy control pregnancies were included. RESULTS: A total of 100 former SGA children and 113 controls with normal weight (AGA) were examined at 1 year of age. Drop-out for 1-year follow-up was 27%. SGA children had significantly higher systolic (92.8 ± 9.8 mmHg vs. 87.5 ± 10.7 mmHg, p = 0.001), diastolic (63.1 ± 8.5 mmHg vs. 60.0 ± 10.3 mmHg, p = 0.028) and mean (73.0 ± 7.8 vs. 69.2 ± 9.7 mmHg, p = 0.004) blood pressure than AGA children. Comparing two breastfeeding periods (0-4 months vs. > 7 months), a downward trend in blood pressure values for longer breastfeeding periods was shown. CONCLUSION: Our study showed that even late-onset small-for-gestational-age fetuses seem to have cardiovascular problems, although they were previously thought to be "healthy". Up to now, blood pressure measurement is not part of indicated health checks in former SGA or even fetal growth-restricted children which should be changed. Further studies are needed to investigate cardiovascular prevention programs in children.
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Enfermedades del Recién Nacido , Ultrasonografía Prenatal , Niño , Femenino , Retardo del Crecimiento Fetal , Edad Gestacional , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional/fisiología , Estudios Longitudinales , Embarazo , Estudios ProspectivosRESUMEN
INTRODUCTION: Helicobacter pylori infection affects approximately 70% of the Chilean population. It is a public health problem whose eradication treatment is part of the explicit health guarantees in Chile. OBJECTIVES: Characterize the most widely used H. pylori first-line eradication therapies in our environment and evaluate their efficacy. METHODS: A retrospective observational study was carried out where, in patients with certified H. pylori infection, the eradication therapy indicated by the treating physician, its efficacy, adherence and adverse effects, in addition to the eradication certification method used, were evaluated. RESULTS: 242 patients and 4 main therapies were analyzed: standard triple therapy, dual therapy, concomitant therapy, and bismuth quadruple therapy. Eradication rates of 81.9% (95% CI 74.44-87.63), 88.5% (95% CI 73.13-95.67), 93.7% (95% CI 78.07-98.44) and 97.6% (95% CI 84.81-99.67) were observed respectively, with concomitant therapy (RR: 1.14; 95% CI 1.01-1.29; p=.028) and quadruple therapy with bismuth (RR: 1.19; 95% CI 1.09-1.31; p<.001) being significantly more effective than standard triple therapy. Regarding the rate of reported adverse effects, it was 58.5% (95% CI 50.66-65.92), 35.4% (95% CI 24.6-48.11), 22.9% (95% CI 81-37.14) and 63.4% (95% CI 47.8-76.64), having the dual and concomitant therapy significantly fewer adverse effects compared with standard therapy. CONCLUSIONS: Quadruple therapies are superior to standard triple therapy and should be considered as first-line treatment in Chile. Dual therapy is promising. More studies will be required to determine which therapies are most cost-effective.
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Infecciones por Helicobacter , Helicobacter pylori , Amoxicilina/uso terapéutico , Antibacterianos/efectos adversos , Bismuto/uso terapéutico , Chile , Quimioterapia Combinada , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Inhibidores de la Bomba de Protones/uso terapéuticoRESUMEN
OBJECTIVES: To: 1. Describe the frequency of viral RNA detection in stools in a cohort of patients infected with SARS-CoV-2, and 2. Perform a systematic review to assess the clearance time in stools of SARS-CoV-2. METHODS: We conducted a prospective cohort study in two centers between March and May 2020. We included SARS-CoV-2 infected patients of any age and severity. We collected seriated nasopharyngeal swabs and stool samples to detect SARS-CoV-2. After, we performed a systematic review of the prevalence and clearance of SARS-CoV-2 in stools (PROSPERO-ID: CRD42020192490). We estimated prevalence using a random-effects model. We assessed clearance time by using Kaplan-Meier curves. RESULTS: We included 32 patients; mean age was 43.7±17.7 years, 43.8% were female, and 40.6% reported gastrointestinal symptoms. Twenty-five percent (8/32) of patients had detectable viral RNA in stools. The median clearance time in stools of the cohort was 11[10-15] days. Systematic review included 30 studies (1392 patients) with stool samples. Six studies were performed in children and 55% were male. The pooled prevalence of viral detection in stools was 34.6% (twenty-four studies, 1393 patients; 95%CI:25.4-45.1); heterogeneity was high (I2:91.2%, Q:208.6; p≤0.001). A meta-regression demonstrates an association between female-gender and lower presence in stools (p=0.004). The median clearance time in stools was 22 days (nineteen studies, 140 patients; 95%CI:19-25). After 34 days, 19.9% (95%CI:11.3-29.7) of patients have a persistent detection in stools. CONCLUSIONS: Detection of SARS-CoV-2 in stools is a frequent finding. The clearance of SARS-CoV-2 in stools is prolonged and it takes longer than nasopharyngeal secretions.
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COVID-19 , SARS-CoV-2 , Adulto , COVID-19/diagnóstico , COVID-19/epidemiología , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , ARN Viral , Esparcimiento de VirusRESUMEN
OBJECTIVE: To evaluate the impact of preoperative cervical length on pregnancy outcome in monochorionic diamniotic twin pregnancies complicated by twin-twin transfusion syndrome that underwent laser surgery or cord occlusion. MATERIALS AND METHODS: Retrospective study of 330 patients stratified by preoperative cervical length (≥25 mm, 16-24 mm,≤15 mm). Maternal characteristics, operative data, and pregnancy outcomes were compared between the cervical length groups as well as between the subgroups of patients with a cervical length≤15 mm according to management (expectant vs. cerclage). RESULTS: A preoperative cervical length≥25 mm was observed in 82% (n=271) of cases, 16-24 mm in 9% (n=29), and≤15 mm in 9% (n=30). Patients with a preoperative cervical length≤15 mm showed shorter median procedure-to-delivery interval (5.5 weeks vs. 11.6 (16-24 mm) vs. 13.0 (≥25 mm); p<0.001); lower median gestational age at delivery (29.5 weeks vs. 34.3 (16-24 mm) vs. 33.4 (≥25 mm); p<0.001); higher rate of preterm delivery<32 weeks (78 vs. 20% (16-24 mm) vs. 31% (≥25 mm); p<0.001); and lower neonatal survival rate of at least one twin (70 vs. 88% (16-24 mm) vs. 93% (≥25 mm); p<0.001). Outcome of patients with a preoperative cervical length≤15 mm was similar regardless of management. CONCLUSION: Monochorionic diamniotic twin pregnancies complicated by twin-twin transfusion syndrome with a preoperative cervical length≤15 mm showed a higher rate of preterm delivery<32 weeks and lower neonatal survival. The role of a cervical cerclage remains unclear.
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Cerclaje Cervical , Transfusión Feto-Fetal , Nacimiento Prematuro , Femenino , Transfusión Feto-Fetal/diagnóstico por imagen , Transfusión Feto-Fetal/cirugía , Edad Gestacional , Humanos , Recién Nacido , Embarazo , Resultado del Embarazo/epidemiología , Embarazo Gemelar , Estudios RetrospectivosRESUMEN
AIM: Members of the working groups on hypertension or cardiovascular disease of the Spanish Societies of Primary Care Physicians (PCPs) [SEMERGEN], Family and Community Medicine [semFYC] and General and Family Physicians [SEMG], conducted a Delphi study to validate with a panel of PCPs with expertise in hypertension several recommendations to optimize teleconsultation in hypertensive patients. MATERIALS AND METHODS: Delphi study based on an online questionnaire with 59 recommendations based on the available evidence and the clinical experience of the authors. RESULTS: 118 PCPs participated in two rounds of the questionnaire (98.3% of the invited physicians), reaching consensus in 53/62 statements (85%). The Primary Care team must proactively select the hypertensive patients suitable for telematic consultation and contact them to set up an appointment. Telematic consultation must begin explaining the reason and aims pursued, continuing with anamnesis, which must explore signs and symptoms of disease worsening, current treatments and level of adherence. In patients with a home blood pressure measurement (HBPM) ≤135/85mmHg, it is recommended to schedule a new telematic appointment in 3-6months. On the contrary, asymptomatic patients with a HBPM ≥135/85mmHg should undergo ambulatory blood pressure monitoring, treatment modification or, in case of warning signs or symptoms, referral to a face-to-face visit or to emergency department. CONCLUSIONS: Teleconsultation can complement face-to-face consultation, constituting an additional tool for the appropriate follow-up of hypertensive patients.
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Hipertensión , Telemedicina , Presión Sanguínea , Monitoreo Ambulatorio de la Presión Arterial/métodos , Técnica Delphi , Humanos , Hipertensión/diagnóstico , Hipertensión/terapia , Atención Primaria de Salud , EspañaRESUMEN
OBJECTIVE: To evaluate left myocardial performance index (MPI) and its time intervals in monochorionic diamniotic (MCDA) twin pairs complicated by selective fetal growth restriction (sFGR) with abnormal (persistent -type II- or intermittent -type III- absent or reversed end-diastolic flow) umbilical artery Doppler. METHODS: Retrospective study including 16 MCDA twin pairs with sFGR type II, 26 MCDA twin pairs with sFGR type III and 42 gestational age-matched uncomplicated MCDA twin pairs in a single tertiary center. Left isovolumetric contraction time (ICT), ejection time (ET), and isovolumetric relaxation time (IRT) were measured and MPI calculated by conventional Doppler at diagnosis of sFGR. RESULTS: In sFGR type II, the smaller twin had shorter ET and prolonged IRT and MPI, while the larger twin showed prolonged ICT and MPI as compared to uncomplicated MCDA twins. In sFGR type III, the smaller twin had shorter ICT and ET, while the larger twin showed prolonged ICT, IRT, and MPI in comparison to controls. CONCLUSION: A differential pattern of MPI time intervals could be observed in MCDA twins with sFGR type II and III. All twins had echocardiographic signs of pressure/volume overload, except the smaller twin type III with shorter systolic times probably reflecting reduced volume load.
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Retardo del Crecimiento Fetal/diagnóstico por imagen , Gemelos , Arterias Umbilicales/anomalías , Adulto , Función del Atrio Izquierdo/fisiología , Estudios de Cohortes , Femenino , Retardo del Crecimiento Fetal/diagnóstico , Humanos , Embarazo , Estudios Retrospectivos , Ultrasonografía Doppler/métodos , Arterias Umbilicales/diagnóstico por imagen , Función Ventricular Izquierda/fisiologíaRESUMEN
INTRODUCTION: To assess the impact of gestational age at term on the association between cerebroplacental ratio (CPR) and operative delivery for intrapartum fetal compromise (IFC) and prognostic performance of CPR to predict operative delivery for IFC. MATERIAL AND METHODS: This was a retrospective cohort study including 2052 singleton pregnancies delivered between 37+0 and 41+6 weeks of gestation in a single tertiary referral center over an 8-year period. CPR was measured within 1 week of delivery. IFC was defined as the presence of persistent pathological cardiotocography pattern or the combination of pathological cardiotocography pattern and fetal scalp pH < 7.20. Operative delivery included instrumental vaginal delivery and cesarean section. Pregnancies were grouped according to birthweight (small for gestational age [SGA, birthweight <10th centile] and appropriate for gestational age [AGA, birthweight 10th-90th centile]) and gestational age by week at delivery. Rates of operative delivery were compared between the subgroups. Prognostic value of CPR was assessed using receiver operating characteristic curve. RESULTS: Of the study cohort, 308 (15%) had a CPR <10th centile, 374 (18%) operative delivery for IFC, and 298 (15%) were SGA at birth. Overall, the rates of operative delivery for IFC were higher in the low CPR group both in SGA (35% vs. 22%; p = 0.023) and in AGA (23% vs. 16%; p = 0.007). According to gestational age by week at delivery, fetuses with low CPR showed higher rates of operative delivery for IFC with advancing gestational age, mainly in pregnancies delivered at 40 weeks (54% vs. 23%; p = 0.004) and at 41 weeks (60% vs. 19%; p = 0.010) for SGA and at 41 weeks (39% vs. 20%; p = 0.001) for AGA. The predictive value of CPR remained stable throughout term and was poor both in SGA and in AGA. CONCLUSIONS: Both SGA and AGA fetuses with low CPR showed higher rates of operative delivery for IFC at term with advancing gestational age. Prognostic value of CPR throughout term was poor.
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Sufrimiento Fetal/diagnóstico por imagen , Arteria Cerebral Media/diagnóstico por imagen , Ultrasonografía Prenatal , Arterias Umbilicales/diagnóstico por imagen , Adulto , Velocidad del Flujo Sanguíneo , Cesárea , Estudios de Cohortes , Femenino , Edad Gestacional , Humanos , Recién Nacido , Arteria Cerebral Media/fisiopatología , Valor Predictivo de las Pruebas , Embarazo , Resultado del Embarazo , Flujo Pulsátil , Estudios Retrospectivos , Factores de Tiempo , Arterias Umbilicales/fisiopatologíaRESUMEN
Plants in the Amaryllidaceae family synthesize a diversity of bioactive alkaloids. Some of these plant species are not abundant and have a low natural multiplication rate. The aims of this work were the alkaloids analysis of a Habranthus cardenasianus bulbs extract, the evaluation of its inhibitory activity against cholinesterases, and to test several propagation strategies for biomass production. Eleven compounds were characterized by GC-MS in the alkaloid extract, which showed a relatively high proportion of tazettine. The known alkaloids tazettine, haemanthamine, and the epimer mixture haemanthidine/6-epi-haemanthidine were isolated and identified by spectroscopic methods. Inhibitory cholinesterases activity was not detected. Three forms of propagation were performed: bulb propagation from seed, cut-induced bulb division, and micropropagated bulbs. Finally, different imbibition and post-collection times were evaluated in seed germination assays. The best propagation method was cut-induced bulb division with longitudinal cuts into quarters (T1) while the best conditions for seed germination were 0-day of post-collection and two days of imbibition. The alkaloids analyses of the H. cardenasianus bulbs showed that they are a source of anti-tumoral alkaloids, especially pretazettine (tazettine) and T1 is a sustainable strategy for its propagation and domestication to produce bioactive alkaloids.
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Alcaloides/análisis , Alcaloides/farmacología , Amaryllidaceae/química , Amaryllidaceae/crecimiento & desarrollo , Inhibidores de la Colinesterasa/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Alcaloides de Amaryllidaceae/análisis , Biomasa , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/química , Cromatografía de Gases y Espectrometría de Masas , Germinación , Estructura Molecular , Fenantridinas/análisis , Extractos Vegetales/química , Extractos Vegetales/farmacología , Raíces de Plantas/crecimiento & desarrollo , Semillas/crecimiento & desarrollo , Factores de TiempoRESUMEN
PURPOSE: Phase-rectified signal averaging method (PRSA) represents an analysis method which applied on fetal cardiotocography (CTG) allows the quantification of the speed of fetal heart rate changes. By calculating the average deceleration capacity (ADC) an assessment of the fetal autonomic nervous system (ANS) is possible. The objective of this study was to test its ability to predict perinatal acidosis. METHODS: A case-control study was performed at a University Hospital in Munich. All intrapartum CTG heart rate tracings saved during a 7-year period were considered for analysis. All neonates born with an umbilical arterial blood pH ≤ 7.10 were considered as cases. Controls were defined as healthy fetuses born with a pH ≥ 7.25. The main matching criteria were gestational age at delivery, parity, birth mode, and birth weight percentile. Exclusion criteria were a planned caesarean section, fetal malformations, and multiple pregnancies. ADC and STV were then calculated during the last 60, the last 45, and the last 30 min intervals prior to delivery. RESULTS: Of all stored birth CTG recordings, 227 cases met the inclusion criteria and were studied. ADC was significantly higher in fetuses born with acidemia (4.85 bpm ± 3.0) compared to controls (3.36 bpm ± 2.2). The area under ROC curve was 0.659 (95% CI 0.608-0.710) for ADC and 0.566 (0.512-0.620) for STV (p = 0.013). CONCLUSIONS: This study confirms that the assessment of ADC using PRSA represents a good additional tool for the prediction of acute fetal acidosis during delivery.
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Acidosis/sangre , Cardiotocografía/métodos , Sangre Fetal/química , Enfermedades Fetales/diagnóstico , Estudios de Casos y Controles , Femenino , Sangre Fetal/citología , Enfermedades Fetales/sangre , Frecuencia Cardíaca Fetal/fisiología , Humanos , Masculino , EmbarazoRESUMEN
PURPOSE: The sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio and uterine artery Doppler have shown to be helpful in the diagnosis of pre-eclampsia (PE). The predictive value of the cerebroplacental ratio (CPR) regarding adverse perinatal outcome (APO) in low-risk pregnancies is intensively discussed. We evaluated the extent to which sFlt-1/PlGF ratio and feto-maternal Doppler may be useful in predicting APO in singleton pregnancies complicated by late-onset PE and/or HELLP syndrome. METHODS: This is a retrospective study from 2010 to 2018 consisting of singleton pregnancies with confirmed diagnosis of late-onset (lo ≥ 34 weeks) PE/HELLP syndrome in which sFlt-1/PlGF ratio and feto-maternal Doppler (mUtA-PI: mean uterine artery pulsatility index and CPR) were determined. The ability of sFlt-1/PlGF ratio, mUtA-PI, CPR and their combination to predict APO or SGA was evaluated using receiver operating characteristic (ROC) curves. RESULTS: 67 patients were included in the final analysis. Of these, sFlt-1/PlGF was > 110 (defining angiogenic lo PE) in 40.3% (27/67), mUtA-PI was above the 95th centile in 34.3% (23/67) patients and CPR was lower than the 5th centile in 10.4% (7/67). Abnormal sFlt-1/PlGF and mUtA-PI as well as CPR were associated with a lower birth weight (BW). Late-preterm birth (< 37 weeks) as well as postnatal diagnosis of small for gestational age (SGA: BW < 3rd centile) was significantly more often in angiogenic lo PE cases. Neither sFlt-1/PIGF nor CPR or mUtA-PI were APO predictors. Only for sFlt-1/PlGF, ROC analysis revealed a significant predictive value for postnatal SGA (AUC = 0.856, p = 0.001, 95% CI 0.75-0.97). There was no statistical added value of combined SGA predictors as compared to sFlt-1/PlGF alone. CONCLUSIONS: In patients with lo PE, adding sFlt-1/PlGF ratio to routine antepartum fetal surveillance may be useful to identify cases of postnatal SGA. However, further prospective studies are warranted to define the role of feto-maternal Doppler and sFlt-1/PlGF ratio as outcome predictors.
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Recién Nacido Pequeño para la Edad Gestacional/sangre , Factor de Crecimiento Placentario/sangre , Preeclampsia/diagnóstico , Proteínas Gestacionales/sangre , Ultrasonografía Doppler/métodos , Arteria Uterina/diagnóstico por imagen , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Adulto , Biomarcadores/sangre , Femenino , Humanos , Recién Nacido , Preeclampsia/sangre , Preeclampsia/metabolismo , Valor Predictivo de las Pruebas , Embarazo , Nacimiento Prematuro , Curva ROC , Estudios RetrospectivosRESUMEN
PURPOSE: Fetal Doppler changes are well characterized in early-onset small-for-gestational-age (SGA) and fetal growth restriction (FGR) but less well characterized where the condition is late-onset. The aim of the study was to evaluate the role of computerized CTG (cCTG)-based short-term variation (STV) in late-onset SGA and FGR as an additional monitoring modality and to establish STV reference ranges in late third trimester healthy pregnancies. METHODS: Of 86 late-onset SGA fetuses diagnosed after 32 weeks, 66 were diagnosed with FGR. 138 healthy pregnancies acted as controls. All underwent umbilical artery pulsatility index (PI), middle cerebral artery PI, cerebroplacental ratio and mean uterine artery PI. cCTG recordings were analyzed by Sonicaid FetalCare software for STV calculation as described by Dawes/Redman. RESULTS: Median interval between inclusion and delivery was 13 (interquantile range = 4-30) days in the FGR group, 22 (12-37) days in the SGA group and 25 (10-40) days in the control group. STV was not different between controls (11.2 ms, 9.7-13.1), late-onset SGA (11.2 ms, 8.1-12.6) and FGR (10.5 ms, 8.5-12.4) fetuses. A greater proportion of late-onset SGA fetuses had STV < 5th percentile (7/86) compared to controls (4/138) (8.1% vs. 2.9%, p = 0.077). In the control group a significant positive correlation was seen between STV, and 1-min (ρ = 0.195, p = 0.026), 5-min (ρ = 0.247, p = 0.004) and 10-min (ρ = 0.211, p = 0.014) Apgar values. CONCLUSIONS: We report no significant difference in STV median values between controls, SGA and FGR pregnancies. However, more SGA fetuses had a low STV compared to controls. Prospective longitudinal studies are needed to investigate if low STV is a useful surveillance method for late-onset FGR.