Prediction of perinatal survival in early-onset fetal growth restriction: role of placental growth factor.

OBJECTIVE: To analyze the ability to predict perinatal survival and severe neonatal morbidity of cases with early-onset fetal growth restriction (eoFGR) using maternal variables, ultrasound parameters and angiogenic markers at the time of diagnosis. METHODS: This was a prospective observational study in a cohort of singleton pregnancies with a diagnosis of eoFGR (< 32 weeks of gestation). At diagnosis of eoFGR, complete assessment was performed, including ultrasound examination (anatomy, biometry and Doppler assessment) and maternal serum measurement of the angiogenic biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). Logistic regression models for the prediction of perinatal survival (in cases diagnosed at < 28 weeks) and severe neonatal morbidity (in all liveborn cases) were calculated. RESULTS: In total, 210 eoFGR cases were included, of which 185 (88.1%) survived perinatally. The median gestational age at diagnosis was 27 + 0 weeks. All cases diagnosed at ≥ 28 weeks survived. In cases diagnosed < 28 weeks, survivors (vs non-survivors) had a higher gestational age (26.1 vs 24.4 weeks), estimated fetal weight (EFW; 626 vs 384 g), cerebroplacental ratio (1.1 vs 0.9), PlGF (41 vs 18 pg/mL) and PlGF multiples of the median (MoM; 0.10 vs 0.06) and lower sFlt-1/PlGF ratio (129 vs 479) at the time of diagnosis (all P < 0.001). The best combination of two variables for predicting perinatal survival was provided by EFW and PlGF MoM (area under the receiver-operating-characteristics curve (AUC), 0.84 (95% CI, 0.75-0.92)). These were also the best variables for predicting severe neonatal morbidity (AUC, 0.73 (95% CI, 0.66-0.80)). CONCLUSIONS: A model combining EFW and maternal serum PlGF predicts accurately perinatal survival in eoFGR cases diagnosed before 28 weeks of gestation. Prenatal prediction of severe neonatal morbidity in eoFGR cases is modest regardless of the model used. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Metástasis de cáncer de células claras renal en cuerdas vocales. Reporte de un caso / Metastasis of renal clear cell carcinoma in vocal cords. A Case report

Introducción: Las metástasis a distancia de tumores primarios a cuerdas vocales son poco frecuentes. Las metástasis a laringe con mayor frecuencia corresponden a melanomas y carcinomas, afectando principalmente a la región supraglótica. Las metástasis a cabeza y cuello de los carcinomas de células renales (CCR) tienen una incidencia de 14-16%. Se presenta el caso de un paciente con metástasis de carcinoma de células claras renal a cuerdas vocales, cuya importancia recae en que es un caso poco frecuente y no existen reportes similares en el país. Paciente masculino, 57 años, con disfonía de 3 meses de evolución. Nasofibroscopía evidencia lesión polipoídea en cuerda vocal y ventrículo izquierdo. Se realiza microcirugía laríngea, enviando muestra a biopsia diferida, resultando lesión metastásica de CCR células claras. Evaluado por nefrología, se pesquisa tumor renal izquierdo sugerente de CCR. Las metástasis de neoplasias remotas a laringe son infrecuentes. Se considera al CCR el tercero en frecuencia respecto a neoplasias infraclaviculares. Éstas se pueden presentar hasta 10 años después del tratamiento del primario. Se recomienda seguimiento a largo plazo y énfasis a nuevos síntomas en región de cabeza y cuello, teniendo en consideración antecedente de CCR en pacientes con disfonía y lesiones polipoídeas en cuerdas vocales.

Introduction: The metastasis of distant site primary tumors to the vocal cords is infrequent. The most frequent source of metastasis to the larynx is melanomas and carcinomas, mainly affecting the supraglottic region. The metastasis to the head and neck of renal cell carcinomas (RCC) has an incidence of 14-16%. To present a case of metastasis of clear renal cell carcinoma to the vocal cords, since it is very infrequent, and there are no similar reports in the country. A male patient, 57 years old, presenting dysphonia for a duration of 3 months. Nasofibroscopy showed a polypoid lesion in the left vocal cord and ventricle. Larynx microsurgery was performed, and a sample was sent for biopsy, which reported a metastatic lesion of RCC clear cells. When assessed by nephrology, a left renal tumor is found, suggesting RCC. The metastasis of distant site neoplasias are infrequent. RCC is considered the third in frequency concerning to infraclavicular neoplasias. These can present up to 10 years after the treatment of the primary. Long term follow-up is recommended, and an emphasis on new symptoms in the head and neck region, considering the history of RCC in patients with dysphonia and polypoid lesions in vocal cords.

Manifestaciones Gastrointestinales de COVID-19: puesta al día y revisión de literatura / Gastrointestinal Manifestations of COVID-19: update and literature review

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus belonging to the beta coronavirus family, it is the cause of the COVID-19 disease and the pandemic that has revolutionized and challenged the medical research profession and health systems around the world. With the first coronavirus SARS-CoV, the important role of the angiotensin 2-converting enzyme (ACE2) in the pathophysiology of the disease caused by the virus was discovered, a discovery that would lay the foundations on which research on the new coronavirus is based. The virus is capable of producing disease with a wide spectrum of clinical presentation, from asymptomatic patients to patients with severe acute respiratory distress syndrome (ARDS) requiring admission to intensive care units (ICU). The most commonly described symptoms are fever, cough, myalgia, and dyspnea. However, and with advances in the knowledge of SARS-CoV-2 infection, it has been discovered that gastrointestinal (GI) symptoms are frequent and have been associated with severe disease. Viral RNA has been found in feces, urine, blood, and other fluids, which could mean that there are other routes of infection that have not been considered a threat by the medical community until now. In this article, an updated bibliographic review of this topic is presented, with articles selected from the PubMed platform.

Epidemiology of COVID-19 in Mexico: from the 27th of February to the 30th of April 2020. / Epidemiología de COVID-19 en México: del 27 de febrero al 30 de abril de 2020.

BACKGROUND: The first case of COVID-19 detected in Mexico was on the 27th of February 2020. On the 30th of April, 64 days after this first diagnosis, the number of patients had increased exponentially, reaching 19 224 confirmed cases and 1859 (9.67%) deaths. In response to this global outbreak, we summarize the current state of our understanding regarding COVID-19 in Mexico. METHODS: We obtained the data from the official website of the Ministry of Health in Mexico. The study period was between the 27th of February and the 30th of April 2020. The cases were confirmed using real-time reverse transcription-polymerase chain reaction, and we analysed epidemiological, demographic and clinical data. RESULTS: In Mexico, most cases of COVID-19 were located in Mexico City. The mean age of the patients was 46 years. Of the 12 656 confirmed cases, most infected individuals were between the ages of 30 and 59 years (65.85%), and there was a higher incidence rate in men (58.18%) than in women (41.82%). The patients who died had one or more comorbidities, mainly hypertension (45.53%), diabetes (39.39%) and obesity (30.4%). In the first 64 days of the epidemic, China had reported 80 304 cases with a mortality rate of 3.66%. CONCLUSIONS: Our results indicate an early transmission of COVID-19 in Mexico. The descriptive epidemiology shows similarities between the cases of COVID-19 in Mexico and those in China. In the same period of the epidemic curve, we observed a reduction in the number of confirmed cases of COVID-19 in Mexico and a higher mortality rate compared with that of China.

Cell-Based Regenerative Endodontics for Treatment of Periapical Lesions: A Randomized, Controlled Phase I/II Clinical Trial.

A randomized controlled phase I/II clinical trial was designed to evaluate the safety and efficacy of encapsulated human umbilical cord mesenchymal stem cells in a plasma-derived biomaterial for regenerative endodontic procedures (REPs) in mature permanent teeth with apical lesions. The trial included 36 patients with mature incisors, canines, or mandibular premolars showing pulp necrosis and apical periodontitis. Patients were randomly and equally allocated between experimental (REP) or conventional root canal treatment (ENDO) groups. On the first visit, cavity access and mechanical preparation of the root canal were performed. Calcium hydroxide medication was used, and the cavity was sealed. Three weeks later, patients were treated following their assigned protocol of ENDO or REP. Clinical follow-up examinations were performed at 6 and 12 mo. Categorical variables were evaluated by Fisher's exact test. Quantitative variables were compared using the Mann-Whitney test. The evolution over time of the percentage of perfusion units and the dimensions of lesion and cortical compromise were explored. After the 12-mo follow-up, no adverse events were reported, and the patients showed 100% clinical efficacy in both groups. Interestingly, in the REP group, the perfusion unit percentage measured by laser Doppler flowmetry revealed an increase from 60.6% to 78.1% between baseline and 12-mo follow-up. Sensitivity tests revealed an increase of the positive pulp response in the REP group at 12-mo follow-up (from 6% to 56% on the cold test, from 0% to 28% on the hot test, and from 17% to 50% on the electrical test). We present the first clinical safety and efficacy evidence of the endodontic use of allogenic umbilical cord mesenchymal stem cells encapsulated in a plasma-derived biomaterial. The innovative approach, based on biological principles that promote dentin-pulp regeneration, presents a promising alternative for the treatment of periapical pathology (ClinicalTrials.gov NCT03102879).

[Epidemiology of COVID-19 in Mexico: from the 27th of February to the 30th of April 2020]. / Epidemiología de COVID-19 en México: del 27 de febrero al 30 de abril de 2020.

BACKGROUND: The first case of COVID-19 detected in Mexico was on the 27th of February 2020. On the 30th of April, 64 days after this first diagnosis, the number of patients had increased exponentially, reaching 19 224 confirmed cases and 1859 (9.67%) deaths. In response to this global outbreak, we summarize the current state of our understanding regarding COVID-19 in Mexico. METHODS: We obtained the data from the official website of the Ministry of Health in Mexico. The study period was between the 27th of February and the 30th of April 2020. The cases were confirmed using real-time reverse transcription-polymerase chain reaction, and we analysed epidemiological, demographic and clinical data. RESULTS: In Mexico, most cases of COVID-19 were located in Mexico City. The mean age of the patients was 46 years. Of the 12 656 confirmed cases, most infected individuals were between the ages of 30 and 59 years (65.85%), and there was a higher incidence rate in men (58.18%) than in women (41.82%). The patients who died had one or more comorbidities, mainly hypertension (45.53%), diabetes (39.39%) and obesity (30.4%). In the first 64 days of the epidemic, China had reported 80 304 cases with a mortality rate of 3.66%. CONCLUSIONS: Our results indicate an early transmission of COVID-19 in Mexico. The descriptive epidemiology shows similarities between the cases of COVID-19 in Mexico and those in China. In the same period of the epidemic curve, we observed a reduction in the number of confirmed cases of COVID-19 in Mexico and a higher mortality rate compared with that of China.

sFlt-1/PlGF ratio and timing of delivery in early-onset fetal growth restriction with antegrade umbilical artery flow.

OBJECTIVE: To analyze the value of the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio in predicting the time to delivery in early-onset fetal growth restriction (FGR) with preserved antegrade umbilical artery (UA) flow at diagnosis. METHODS: This was a prospective observational single-center cohort study of pregnancies with early-onset (< 32 + 0 weeks) FGR and antegrade UA flow, in which maternal serum sFlt-1/PlGF ratio was determined at diagnosis. FGR was defined as estimated fetal weight < 3rd centile or < 10th centile with UA pulsatility index > 95th centile, fetal middle cerebral artery pulsatility index < 5th centile or cerebroplacental ratio < 5th centile. The previously described sFlt-1/PlGF ratio cut-off value of 85 for facilitating the diagnosis of pre-eclampsia was assessed in the prediction of the need to deliver in < 1 week and ≥ 4 weeks. RESULTS: In total, 120 cases were included. There were 116 (96.7%) liveborn neonates and 108 (90.0%) perinatal survivors. Median (interquartile range (IQR)) gestational age at diagnosis of early-onset FGR was 27.1 (25.7-29.4) weeks. Median (IQR) sFlt-1/PlGF ratio at diagnosis was 196 (84-474). Ninety (75.0%) cases had a sFlt-1/PlGF ratio ≥ 85. Among pregnancies with a liveborn neonate, median (IQR) interval to delivery in the groups with sFlt-1/PlGF ratio < 85 and ≥ 85 was 41 (22-54) days and 11 (4-20) days, respectively (P < 0.01). The probability of having to deliver within 1 week after diagnosis was 0% and 35.6% in those with sFlt-1/PlGF ratio < 85 and ≥ 85, respectively (P = 0.03), and the probability of delaying delivery for ≥ 4 weeks was 72.4% and 19.5%, respectively (P < 0.01). CONCLUSION: sFlt-1/PlGF ratio < 85 at diagnosis of early-onset FGR with antegrade UA flow identifies a group of pregnancies in which the need to deliver within 1 week is very low and the interval to delivery is expected to be prolonged for ≥ 4 weeks in > 70% of cases. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Susceptibility to organophosphates pesticides and the development of infectious-contagious respiratory diseases.

In this paper we develop an SIRS compartmental model to investigate the dynamic interplay between pesticide intoxication and the spread of infectious-contagious respiratory diseases. We are particularly interested in investigating three levels of genetic susceptibility to pesticide intoxication. The genotypic distribution of susceptibility to pesticide intoxication, is proposed and parameterized according to ethnic variation using real population data from published studies, and we assume that pesticide intoxication increases susceptibility to infection with a respiratory pathogen. We use mathematical models to illustrate the impact of this distribution on the spread of hypothetical respiratory disease in a population exposed to the organophosphate pesticide. In this context, we show how an initial basic reproductive number below the epidemic threshold of 1.0 could be enhanced to support epidemic outbreaks in agricultural populations that employ chlorpyrifos pesticides. We further illustrate our modeling framework to study the effect of ethnic group variation in Singapore (Malay, Indian and Chinese) using genetic distribution data from published studies.

Determinación de infecciones del tracto urinario en ancianos del asilo Santa Rita de la ciudad de Sucre / Determination of urinary tract infections in the elderly of the asylum Santa Rita of Sucre

La infección del tracto urinari (ITU) es un problema que se ve con frecuencia en el adulto mayor, donde la incidencia llega hasta un 50%, debido principalmente a la postración, las deficiencias en la higiene y a los procedimientos a los que muchas veces son sometidos. El estudio tuvo como objetivo determinar la frecuencia de ancianos con infecciones del tracto urinario (ITU) en el hogar Santa Rita. Participaron 29, de los 43 residentes del hogar Santa Rita, se recolectó la orina en frascos colectores y posteriormente se realizó un examen general de orina y tinción de Gram. De las 29 muestras de orina, 3 muestras dieron positivo para Infecciones del tracto Urinarias (ITU) siendo de estas tres, dos mujeres y un varón. Por lo que se puede señalar una prevalencia del 10,3% de ITU en el hogar Santa Rita.

Urinary tract infection (UTI) is a problem that is frequently seen in the elderly, where the incidence reaches up to 50%, mainly due to prostration, deficiencies in hygiene and procedures that are often submitted. The study aimed to determine the frequency of elderly people with urinary tract infections (UTI) in the Santa Rita home. Of the 43 residents of the Santa Rita home, 29 participated. The urine was collected in collection bottles and subsequently a general urine examination and Gram stain were performed. Of the 29 urine samples, 3 samples were positive for Urinary Tract Infections (UTI), of these three, two women and one man. Therefore, a prevalence of 10.3% of UTI in the Santa Rita home can be pointed out.

Dynamics between infectious diseases with two susceptibility conditions: A mathematical model.

This paper presents a novel epidemiological transmission model of a population affected by two different susceptible-infected-susceptible infectious diseases. For each disease, individuals fall into one of the two susceptibility conditions in which one of the diseases has the highest occurrence level. This model is unique in assuming that: (a) if an individual is infected by one disease, their susceptibility to the other disease is increased; (b) when an individual recovers from a disease they become less susceptible to it, i.e. they acquire partial immunity. The model captures these two assumptions by utilizing a coupled system of differential equations. Dynamic analysis of the system is based on basic reproductive number theory, and pattern visualization was performed using numerical simulation.

Anemia, hiponatremia, hipoalbuminemia y déficit de vitamina K como factores de riesgo para osteoporosis / Anemia, hyponatremia, hypoalbuminemia and vitamin k deficit as risk factors for osteoporosis

La Osteoporosis es un síndrome altamente prevalente en la población mayor, tanto la que ha sufrido fracturas como la que no. Aunque con frecuencia se le relaciona con la menopausia, existen varios otros elementos involucrados en su génesis. Estos frecuentemente coexisten en diversa proporción y son, por lo general, oligosintomáticos o generan signosintomatología muy inespecífica. Esto hace que su diagnóstico y tratamiento se retrase u omita, aumentando el riesgo de caídas y fracturas, y dificultando los procesos de consolidación ósea. Aunque su nivel de evidencia es aún diverso, frecuentemente son hallados cuando se implementa su búsqueda en pacientes mayores fracturados. Por lo que, con independencia de si su relación con la osteoporosis es o no significativa, conviene buscarlos y manejarlos por el riesgo que constituyen por sí mismos. En esta revisión nos referiremos a cuatro de estas condiciones: Hipoalbuminemia, hiponatremia, anemia y deficiencia de vitamina K.

Osteoporosis is very prevalent in the aged and is seen in both those who have suffered fractures and those who have not. Frequently related to the menopause, there are other elements involved in its pathogenesis. These frequently co-exist and are, generally, oligo-symptomatic or have non-specific symptomatology. This causes delays or omissions in their diagnosis and treatment, thereby increasing the risk of falls and fractures and interfering with bone consolidation. Although their evidence levels are diverse, these factors are frequently to be found once directly looked for in the aged fracture patient. Therefore, even though their relation to the osteoporosis may not be significant, it is best to test for them and treat them for the risk they present. In this review we look at four of these conditions: hypoalbuminemia, hyponatremia, anemia and vitamin K deficiency

Clinical implementation of the sFlt-1/PlGF ratio to identify preeclampsia and fetal growth restriction: A prospective cohort study.

OBJECTIVE: To analyze the usefulness of a clinical protocol for early detection of preeclampsia and/or fetal growth restriction (PE/FGR) using, in previously selected pregnancies, the measurement of the sFlt-1/PlGF ratio at 24-28 weeks of gestation. STUDY DESIGN: Prospective observational cohort study carried out in a single tertiary hospital in Spain. 5601 consecutive singleton pregnancies with complete follow-up were included. High-risk women for PE/FGR were selected by combining data from maternal history and second trimester uterine artery Doppler. Subsequently these patients underwent intensive monitoring, including the measurement of the sFlt-1/PlGF ratio at 24-28 weeks to predict PE/FGR. MAIN OUTCOME MEASURES: Early, intermediate and late PE/FGR (delivery <32 + 0, 32 + 0 - <36 + 0 and ≥36 + 0 weeks, respectively). RESULTS: Overall incidence of early, intermediate and late PE/FGR was 0.3%, 0.7% and 3.2%, respectively, being higher in the 4.3% of women selected for intensive monitoring: 5.8%, 8.7% and 15.4%, respectively (all p < 0.001). The area under the curve (AUC) with 95%CI of the sFlt-1/PlGF ratio for detecting early PE/FGR was 0.98 (0.97-1.00), and the sFlt-1/PlGF ratio >95th centile showed a sensitivity (%) of 100 (95%CI, 78.5-100) and specificity (%) of 80.6 (95%CI, 75.0-85.2). The AUC of the sFlt-1/PlGF ratio for detecting intermediate and late PE/FGR was of 0.87 (95%CI, 0.77-0.97) and 0.68 (95%CI, 0.58-0.79), respectively. CONCLUSION: A contingent strategy of measuring the sFlt-1/PlGF ratio at 24-28 weeks in women previously selected by clinical factors and uterine artery Doppler enables an accurate prediction of PE/FGR. This performance is optimal to predict PE/FGR requiring delivery before 32 weeks.

Longitudinal change of sFlt-1/PlGF ratio in singleton pregnancy with early-onset fetal growth restriction.

OBJECTIVE: To describe the evolution of soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) ratio in the last 5 weeks prior to delivery in singleton pregnancy complicated by early-onset fetal growth restriction (FGR), with or without pre-eclampsia (PE). METHODS: This was a prospective observational cohort study of early-onset FGR cases that underwent serial assessment of maternal serum sFlt-1/PlGF ratio from diagnosis to delivery. Measurements were made at weekly intervals and within the last 48 h before birth. Absolute values and percentage increase between time intervals were computed, and previously described cut-off values of 38 (suspicion of PE), 85 (aids diagnosis of PE) and 655 (high risk for imminent delivery) were used for analysis of the sFlt-1/PlGF ratio. We compared findings between cases with early-onset FGR only (n = 37) and those that additionally developed PE (n = 36). RESULTS: Overall perinatal survival was 63/73 (86.3%). A sFlt-1/PlGF ratio above 38 was observed 4 weeks before delivery in most FGR-only and FGR with PE cases (73% and 100%, respectively), but absolute values of sFlt-1/PlGF were significantly higher in FGR cases with PE. Extremely elevated values of the ratio (≥ 655) within the last 48 h before delivery were found in 65% of cases of FGR with PE, but in only 8% of isolated FGR cases (P < 0.001). CONCLUSION: Elevated sFlt-1/PlGF was observed in most early-onset FGR pregnancies from 4 weeks before delivery, and values were even higher if there was concurrent PE. However, serial measurements of the ratio were of limited value, being useful only to anticipate the need for imminent delivery in cases of FGR with PE when sFlt-1/PlGF values ≥ 655 were reached. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

On the origins and genetic diversity of South American chickens: one step closer.

Local chicken populations are a major source of food in the rural areas of South America. However, very little is known about their genetic composition and diversity. Here, we analyzed five populations from South America to investigate their maternal genetic origin and diversity, hoping to mitigate the lack of information on local chicken populations from this region. We also included three populations of chicken from the Iberian Peninsula and one from Easter Island, which are potential sources of the first chickens introduced in South America. The obtained sequencing data from South American chickens indicate the presence of four haplogroups (A, B, E and D) that can be further subdivided into nine sub-haplogroups. Of these, four (B1, D1a, E1a(b), E1b) were absent from local Iberian Peninsula chickens and one (D1a) was present only on Easter Island. The presence of the sub-haplogroups A1a(b) and E1a(b) in South America, previously only observed in Eastern Asia, and the significant population differentiation between Iberian Peninsula and South American populations, suggest a second maternal source of the extant genetic pool in South American chickens.

Familial dilated cardiomyopathy: A multidisciplinary entity, from basic screening to novel circulating biomarkers.

Idiopathic dilated cardiomyopathy has become one of the most prevalent inherited cardiomyopathies over the past decades. Genetic screening of first-degree relatives has revealed that 30-50% of the cases have a familial origin. Similar to other heart diseases, familial dilated cardiomyopathy is characterized by a high genetic heterogeneity that complicates family studies. Cli'nical screening, 12-lead electrocardiogram and transthoracic echocardiogram are recommended for patients and first-degree family members. Magnetic resonance also needs to be considered. Genetic technologies have become fundamental for the clinical management of this disease. New generation sequencing methods have made genetic testing feasible for extensive panels of genes related to the disease. Recently, new imaging modalities such as speckle-tracking, strain and strain rate or magnetic resonance, and circulating biomarkers such as non-coding RNAs, have emerged as potential strategies to help cardiologists in their clinical practice. Imaging, genetic and blood-based techniques should be considered together in the evaluation and testing of familial dilated cardiomyopathy. Here, we discuss the current procedures and novel approaches for the clinical management of familial dilated cardiomyopathy.

Analysis of cell-free DNA in maternal blood in screening for fetal aneuploidies: updated meta-analysis.

OBJECTIVE: To review clinical validation or implementation studies of maternal blood cell-free (cf) DNA analysis and define the performance of screening for fetal trisomies 21, 18 and 13 and sex chromosome aneuploidies. METHODS: Searches of PubMed, EMBASE and The Cochrane Library were performed to identify all peer-reviewed articles on cfDNA testing in screening for aneuploidies between January 2011, when the first such study was published, and 4 January 2015. RESULTS: In total, 37 relevant studies were identified and these were used for the meta-analysis on the performance of cfDNA testing in screening for aneuploidies. These studies reported cfDNA results in relation to fetal karyotype from invasive testing or clinical outcome. Weighted pooled detection rates (DR) and false-positive rates (FPR) in singleton pregnancies were 99.2% (95% CI, 98.5-99.6%) and 0.09% (95% CI, 0.05-0.14%), respectively, for trisomy 21, 96.3% (95% CI, 94.3-97.9%) and 0.13% (95% CI, 0.07-0.20) for trisomy 18, 91.0% (95% CI, 85.0-95.6%) and 0.13% (95% CI, 0.05-0.26%) for trisomy 13, 90.3% (95% CI, 85.7-94.2%) and 0.23% (95% CI, 0.14-0.34%) for monosomy X and 93.0% (95% CI, 85.8-97.8%) and 0.14% (95% CI, 0.06-0.24%) for sex chromosome aneuploidies other than monosomy X. For twin pregnancies, the DR for trisomy 21 was 93.7% (95% CI, 83.6-99.2%) and the FPR was 0.23% (95% CI, 0.00-0.92%). CONCLUSION: Screening for trisomy 21 by analysis of cfDNA in maternal blood is superior to that of all other traditional methods of screening, with higher DR and lower FPR. The performance of screening for trisomies 18 and 13 and sex chromosome aneuploidies is considerably worse than that for trisomy 21.

Screening for trisomies 21, 18 and 13 by cell-free DNA analysis of maternal blood at 10-11 weeks' gestation and the combined test at 11-13 weeks.

OBJECTIVE: To examine in a general population the performance of cell-free DNA (cfDNA) testing for trisomies 21, 18 and 13 at 10-11 weeks' gestation and compare it to that of the combined test at 11-13 weeks. METHODS: In 2905 singleton pregnancies, prospective screening for trisomies was performed by chromosome-selective sequencing of cfDNA in maternal blood at 10-11 weeks' gestation and by the combined test at 11-13 weeks' gestation. RESULTS: Median maternal age of the study population was 36.9 (range, 20.4-51.9) years. Results from cfDNA analysis were provided for 2851 (98.1%) cases and these were available within 14 days from sampling in 2848 (98.0%) cases. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or clinical examination of the neonates. Of the 2785 pregnancies with a cfDNA result and known trisomic status, cfDNA testing correctly identified all 32 cases with trisomy 21, nine of 10 with trisomy 18 and two of five with trisomy 13, with false-positive rates of 0.04%, 0.19% and 0.07%, respectively. In cases with discordant results between cfDNA testing and fetal karyotype, the median fetal fraction was lower than in those with concordant results (6% vs 11%). Using the combined test, the estimated risk for trisomy 21 was ≥ 1/100 in all trisomic cases and in 4.4% of the non-trisomic pregnancies. CONCLUSION: The performance of first-trimester cfDNA testing for trisomies 21 and 18 in the general population is similar to that in high-risk pregnancies. Most false-positive and false-negative results from cfDNA testing could be avoided if the a priori risk from the combined test is taken into account in the interpretation of individual risk.

Fetal fraction of cell-free DNA in maternal plasma in the prediction of spontaneous preterm delivery.

OBJECTIVES: To investigate whether, in pregnancies complicated by spontaneous preterm delivery, fetal fraction of cell-free DNA (cfDNA) in maternal plasma at 11-13 weeks' gestation is altered and if this measurement could be useful in the prediction of preterm delivery. METHODS: Fetal fraction of cfDNA was measured at 10 + 0 to 13 + 6 weeks' gestation in 3169 pregnancies, 3066 (96.7%) that delivered at ≥ 37 weeks and 103 (3.3%) with spontaneous delivery at < 37 weeks, including 21 that delivered at < 34 weeks and 82 that delivered at 34-37 weeks. The measured fetal fraction was converted to multiples of the median (MoM), corrected for maternal characteristics and gestational age, and the Mann-Whitney U-test was used to determine the significance of differences in the median values in the spontaneous preterm delivery groups from that in the term delivery group. RESULTS: In the spontaneous preterm delivery groups (< 34 weeks' gestation, 34-37 weeks, < 37 weeks), compared to the term delivery group, there was no significant difference in the median fetal fraction MoM (1.004, 0.922 and 0.946, respectively, vs 1.015). CONCLUSION: Measurement of fetal fraction in maternal plasma at 11-13 weeks' gestation is not predictive of spontaneous preterm delivery.

Umbilical cord serum lipids between early and late clamping in full-term newborns. A systematic assignment treatment group.

OBJECTIVE: The aim of the current study was to determine any relationship between the timing of clamping of the umbilical cord and the lipid levels circulating in umbilical artery and vein. METHODS: We studied a clinical trial with systematic assignment in 229 single-fetus full-term deliveries with normal gestational course and spontaneous delivery; out of these, 111 were subjected to early clamping (EC, within 10 s of delivery) and 118 to late clamping (LC, at 2 min). In all cases, total cholesterol (TC), triglycerides (TG), and phospholipids were measured in sera from umbilical artery and vein. RESULTS: TC and TG values were significantly higher in the EC group than in the LC group in both umbilical artery and vein. Comparing values between umbilical artery and vein in the two clamping groups, in the EC group, all studied lipids TC, TG and phospholipids were significantly higher in vein than in artery. In the LC group, only TC was higher in vein. CONCLUSION: Umbilical cord lipid levels are related to the timing of umbilical cord clamping, finding which is noteworthy, because they are essential component of postnatal development. Our study confirms that delivery acts as an important modifier of fetal lipid levels.

Tumor-derived inducible heat-shock protein 70 (HSP70) is an essential component of anti-tumor immunity.

The anti-apoptotic function and tumor-associated expression of heat-shock protein 70 (HSP70) is consistent with HSP70 functioning as a survival factor to promote tumorigenesis. However, its immunomodulatory activities to induce anti-tumor immunity predict the suppression of tumor growth. Using the Hsp70.1/3(-/-)(Hsp70(-/-)) mouse model, we observed that tumor-derived HSP70 was neither required for cellular transformation nor for in vivo tumor growth. Hsp70(-/-) murine embryonic fibroblasts (MEFs) were transformed by E1A/Ras and generated tumors in immunodeficient hosts as efficiently as wild-type (WT) transformants. Comparison of Bcr-Abl-mediated transformation of WT and Hsp70(-/-) bone marrow and progression of B-cell leukemogenesis in vivo revealed no differences in disease onset or survival rates, and Eµ-Myc-driven lymphoma in Hsp70(-/-) mice was phenotypically indistinguishable from that in WT Eµ-Myc mice. However, Hsp70(-/-) E1A/Ras MEFs generated significantly larger tumors than their WT counterparts in C57BL/6 J immune-competent hosts. Concurrent with this was a reduction in intra-tumoral infiltration of innate and adaptive immune cells, including macrophages and CD8(+) T cells. Evaluation of several potential mechanisms revealed an HSP70-chemokine-like activity to promote cellular migration. These observations support a role for tumor-derived HSP70 in facilitating anti-tumor immunity to limit tumor growth and highlight the potential consequences of anti-HSP70 therapy as an efficacious anti-cancer strategy.