Low complement levels are related to poor obstetric outcomes in women with obstetric antiphospholipid syndrome. The EUROAPS Registry Study Group.

INTRODUCTION: Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disease related to antiphospholipid antibodies (aPL) with primaryinflammatory injury followed by clot cascade activation and thrombus formation. Complement system activation and their participation in aPL-related thrombosis is unclosed. METHODS: We haveanalysed adverse pregnancy outcomes (APO) related to low complement (LC) levels in a cohort of 1048 women fulfilling classification criteria for OAPS. RESULTS: Overall, 223 (21.3%) women presented LC values, during pregnancy. The length of pregnancy was shorter in OAPS women with LC compared to those with normal complement (NC) (median: 33 weeks, interquartile range: [24-38] vs. 35 weeks [27-38]; p = 0.022). Life new-born incidence was higher in patients with NC levels than in those with LC levels (74.4% vs. 67.7%; p = 0.045). Foetal losses were more related to women with triple or double aPL positivity carrying LC than NC values (16.3% vs. 8.0% NC; p = 0.027). Finally, some placental vasculopathies were affected in OAPS patients with LC as late Foetal Growth Restriction (FGR >34 weeks) rise to 7.2% in women with LC vs. 3.2% with NC (p = 0.007). DISCUSSION: Data from our registry indicate that incidence of APO was higher in OAPS women with LC levels and some could be reverted by the correct treatment.

Predictive Model for Preeclampsia Combining sFlt-1, PlGF, NT-proBNP, and Uric Acid as Biomarkers.

N-terminal pro-brain natriuretic peptide (NT-proBNP) and uric acid are elevated in pregnancies with preeclampsia (PE). Short-term prediction of PE using angiogenic factors has many false-positive results. Our objective was to validate a machine-learning model (MLM) to predict PE in patients with clinical suspicion, and evaluate if the model performed better than the sFlt-1/PlGF ratio alone. A multicentric cohort study of pregnancies with suspected PE between 24+0 and 36+6 weeks was used. The MLM included six predictors: gestational age, chronic hypertension, sFlt-1, PlGF, NT-proBNP, and uric acid. A total of 936 serum samples from 597 women were included. The PPV of the MLM for PE following 6 weeks was 83.1% (95% CI 78.5−88.2) compared to 72.8% (95% CI 67.4−78.4) for the sFlt-1/PlGF ratio. The specificity of the model was better; 94.9% vs. 91%, respectively. The AUC was significantly improved compared to the ratio alone [0.941 (95% CI 0.926−0.956) vs. 0.901 (95% CI 0.880−0.921), p < 0.05]. For prediction of preterm PE within 1 week, the AUC of the MLM was 0.954 (95% CI 0.937−0.968); significantly greater than the ratio alone [0.914 (95% CI 0.890−0.934), p < 0.01]. To conclude, an MLM combining the sFlt-1/PlGF ratio, NT-proBNP, and uric acid performs better to predict preterm PE compared to the sFlt-1/PlGF ratio alone, potentially increasing clinical precision.

Cardiac dysfunction and remodeling regulated by anti-angiogenic environment in patients with preeclampsia: the ANGIOCOR prospective cohort study protocol.

BACKGROUND: Cardiovascular diseases (CVD) are cause of increased morbidity and mortality in spite of advances for diagnosis and treatment. Changes during pregnancy affect importantly the maternal CV system. Pregnant women that develop preeclampsia (PE) have higher risk (up to 4 times) of clinical CVD in the short- and long-term. Predominance of an anti-angiogenic environment during pregnancy is known as main cause of PE, but its relationship with CV complications is still under research. We hypothesize that angiogenic factors are associated to maternal cardiac dysfunction/remodeling and that these may be detected by new cardiac biomarkers and maternal echocardiography. METHODS: Prospective cohort study of pregnant women with high-risk of PE in first trimester screening, established diagnosis of PE during gestation, and healthy pregnant women (total intended sample size n = 440). Placental biochemical and biophysical cardiovascular markers will be assessed in the first and third trimesters of pregnancy, along with maternal echocardiographic parameters. Fetal cardiac function at third trimester of pregnancy will be also evaluated and correlated with maternal variables. Maternal cardiac function assessment will be determined 12 months after delivery, and correlation with CV and PE risk variables obtained during pregnancy will be evaluated. DISCUSSION: The study will contribute to characterize the relationship between anti-angiogenic environment and maternal CV dysfunction/remodeling, during and after pregnancy, as well as its impact on future CVD risk in patients with PE. The ultimate goal is to improve CV health of women with high-risk or previous PE, and thus, reduce the burden of the disease. TRIAL REGISTRATION: NCT04162236.

Soluble fms-like tyrosine kinase to placental growth factor ratio in different stages of early-onset fetal growth restriction and small for gestational age.

INTRODUCTION: Increased soluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF) has been demonstrated in early-onset fetal growth restriction (FGR) and small for gestational age (SGA). sFlt-1/PlGF cut-offs have been described to assess preeclampsia severity; however, sFlt-1/PlGF values present in early-onset SGA and different FGR severity stages remain unknown. Hence, the objective of this study was to describe and compare the sFlt-1/PlGF values and pregnancy outcomes among early-onset SGA/FGR stages. MATERIAL AND METHODS: This is a prospective case-control study conducted at Vall d'Hebron University Hospital. Singleton pregnancies with estimated fetal weight <10th centile and a control group of uncomplicated pregnancies between 20+0 and 31+6  weeks of gestation were enrolled. Study women were classified at diagnosis into different stages, according to estimated fetal weight centile and Doppler ultrasound. sFlt-1/PlGF serum concentrations were measured at diagnosis and, together with pregnancy outcomes, were compared among FGR severity stages, SGA, and controls. Finally, correlations between sFlt-1/PlGF values and time to delivery, gestational age at delivery, days of neonatal admission, and birthweight z-scores were investigated. RESULTS: Among the 207 women enrolled, 32 (15.4%) had uncomplicated pregnancies, 49 (23.7%) pregnancies showed SGA, and 126 (60.9%) involved FGR (92 being stage I, 17 stage II, and 17 stage III). SGA and controls had similar median sFlt-1/PlGF values (25.7 vs 27.1, P > .05) and pregnancy outcomes. However, all FGR stages had significantly poorer outcomes and greater sFlt-1/PlGF values than those of SGA and controls. Furthermore, median values differed significantly among all FGR severity stages (9.76 for stage I; 284.3 for stage II, and 625.02 for stage III, P < .05) increasing with FGR severity as well as the frequency of adverse pregnancy outcomes. Additionally, a significant correlation was found between greater sFlt-1/PlGF ratio values and gestational age at delivery, time from diagnosis to delivery, birthweight z-scores, and time in neonatal intensive care unit (r = -.637, r = -.576, r = -.161, and r = .311, respectively). CONCLUSIONS: Values of sFlt-1/PlGF at diagnosis permit early-onset FGR/SGA severity classification with good correlation with Doppler ultrasound findings and the occurrence of adverse outcomes. Thus, sFlt-1/PlGF could aid in early-onset FGR/SGA severity classification and clinical management when Doppler assessment is not feasible.

Supply chains for processed potato and tomato products in the United States will have enhanced resilience with planting adaptation strategies.

Food systems are increasingly challenged to meet growing demand for specialty crops due to the effects of climate change and increased competition for resources. Here, we apply an integrated methodology that includes climate, crop, economic and life cycle assessment models to US potato and tomato supply chains. We find that supply chains for two popular processed products in the United States, French fries and pasta sauce, will be remarkably resilient, through planting adaptation strategies that avoid higher temperatures. Land and water footprints will decline over time due to higher yields, and greenhouse gas emissions can be mitigated by waste reduction and process modification. Our integrated methodology can be applied to other crops, health-based consumer scenarios (fresh versus processed) and geographies, thereby informing decision-making throughout supply chains. Employing such methods will be essential as food systems are forced to adapt and transform to become carbon neutral due to the imperatives of climate change.

Angiogenic Factors and Long-Term Cardiovascular Risk in Women That Developed Preeclampsia During Pregnancy.

Preeclampsia is caused by placental impairment with increased expression of sFlt-1 (soluble fms-like tyrosine kinase 1) and decreased PlGF (placental growth factor); it has been associated with cardiovascular morbidity and mortality later in life, but the underlying mechanism remains unknown. The aim of this study was to determine whether sFlt-1 and PlGF levels during preeclampsia are associated to long-term cardiovascular risk. We prospectively recruited 43 women with previous preeclampsia and 21 controls with uncomplicated pregnancies. Cardiovascular risk assessment ≈12 years later included maternal hemodynamic, cardiac function and structure, biomarker analysis, and carotid-intima thickness evaluation. Women with previous preeclampsia had higher prevalence of hypertensive disorders and dyslipidemia than controls. In addition, they had worse global longitudinal strain, thicker left ventricular septal and posterior walls, more myocardial mass and increased carotid intima-media thickness compared with controls. PlGF during pregnancy correlated positively with high-density lipoprotein (r=0.341; P=0.006), and negatively with global longitudinal strain (r=-0.581; P<0.001), carotid intima-media thickness (r=-0.251; P=0.045), and mean arterial blood pressure (r=-0.252; P=0.045), when adjusted by study group. sFlt correlated negatively with high-density lipoprotein (r=-0.372; P=0.002) and apolipoprotein A-1 (r=-0.257; P=0.040), and positively with carotid intima-media thickness (r=0.269; P=0.032) and left ventricular posterior wall thickness (r=0.368; P=0.003). The antiangiogenic state present in preeclampsia is related to greater prevalence of cardiovascular risk factors ≈12 years after delivery. The knowledge of altered angiogenic factors may help detect women with a higher risk for premature cardiovascular disease, who will require earlier follow-up after delivery.

Comparative study of obstetric antiphospholipid syndrome (OAPS) and non-criteria obstetric APS (NC-OAPS): report of 1640 cases from the EUROAPS registry.

OBJECTIVES: To compare clinical features, laboratory data and fetal-maternal outcomes between 1000 women with obstetric APS (OAPS) and 640 with aPL-related obstetric complications not fulfilling Sydney criteria (non-criteria OAPS, NC-OAPS). METHODS: This was a retrospective and prospective multicentre study from the European Registry on Obstetric Antiphospholipid Syndrome. RESULTS: A total of 1650 women with 5251 episodes, 3601 of which were historical and 1650 latest episodes, were included. Altogether, 1000 cases (OAPS group) fulfilled the Sydney classification criteria and 650 (NC-OAPS group) did not. Ten NC-OAPS cases were excluded for presenting thrombosis during follow-up. All cases were classified as category I (triple positivity or double positivity for aPL) or category II (simple positivity). Overall, aPL laboratory categories showed significant differences: 29.20% in OAPS vs 17.96% in NC-OAPS (P < 0.0001) for category I, and 70.8% in OAPS vs 82% in NC-OAPS (P < 0.0001) for category II. Significant differences were observed when current obstetric complications were compared (P < 0.001). However, major differences between groups were not observed in treatment rates, livebirths and thrombotic complications. In the NC-OAPS group, 176/640 (27.5%) did not fulfil Sydney clinical criteria (subgroup A), 175/640 (27.34%) had a low titre and/or non-persistent aPL positivity but did meet the clinical criteria (subgroup B) and 289/640 (45.15%) had a high aPL titre but did not fulfil Sydney clinical criteria (subgroup C). CONCLUSION: Significant clinical and laboratory differences were found between groups. Fetal-maternal outcomes were similar in both groups when treated. These results suggest that we could improve our clinical practice with better understanding of NC-OAPS patients.

Photochemical emission and fixation of NOX gases in soils.

Gaseous nitrogen oxides (NOx), which result from the combustion of fossil fuels, volcanic eruptions, forest fires, and biological reactions in soils, not only affect air quality and the atmospheric concentration of ozone, but also contribute to global warming and acid rain. Soil NOx emissions have been largely ascribed to soil microbiological processes; but there is no proof of abiotic catalytic activity affecting soil NO emissions. We provide evidence of gas exchange in soils involving emissions of NOx by photochemical reactions, and their counterpart fixation through photocatalytic reactions under UV-visible irradiation. The catalytic activity promoting NOx capture as nitrate varied widely amongst different soil types, from low in quartzitic sandy soils to high in iron oxide and TiO2 rich soils. Clay soils with significant amounts of smectite also exhibited high rates of NOx sequestration and fixed amounts of N comparable to that of NO (nitric oxide) losses through biotic reactions. In these soils, a flux of 100 µg NNO m-2 h-1, as usually found in most ecosystems, could be reduced by these photochemical reactions by more than 60%. This mechanism of N fixation provides new insight into the nitrogen cycle and may inspire alternative strategies to reduce NO emissions from soils.

Different Responses of Various Chlorophyll Meters to Increasing Nitrogen Supply in Sweet Pepper.

Intensive vegetable production is commonly associated with excessive nitrogen (N) fertilization and associated environmental problems. Monitoring of crop N status can enhance crop N management. Chlorophyll meters (CMs) could be used to monitor crop N status because leaf chlorophyll (chl) content is strongly related to crop N status. To monitor crop N status, relationships between CM measurements and leaf chl content require evaluation, particularly when excessive N is supplied. The SPAD-502 meter, atLEAF+ sensor, MC-100 Chlorophyll Concentration Meter, and Multiplex sensor were evaluated in sweet pepper with different N supply, throughout the crop, ranging from very deficient to very excessive. CM measurements of all sensors and indices were strongly and positively related to leaf chlorophyll a + b content with curvilinear relationships over the entire range of chl measured (∼0-80 µg cm-2). Measurements with the SPAD-502, and atLEAF+, and of the Multiplex's simple fluorescence ratio index (SFR) had asymptotic responses to increasing leaf chl. In contrast, the MC-100's chlorophyll content index (CCI) had a progressively increasing response. At higher chlorophyll a + b contents (e.g., >40 µg cm-2), SPAD-502, atLEAF+ and SFR measurements tended to saturate, which did not occur with CCI. Leaf chl content was most accurately estimated by CCI (R 2 = 0.87), followed by the SPAD-502 meter (R 2 = 0.85). The atLEAF+ sensor was the least accurate (R 2 = 0.76). For leaf chl estimation, CCI measured with the MC-100 meter was the most effective of the four sensors examined because it: (1) most accurately estimated leaf chl content, and (2) had no saturation response at higher leaf chl content. For non-saturating leaf chl content (∼0-40 µg cm-2), all indices were sensitive indicators. As excessive applications of N are frequent in intensive vegetable crop production, the capacity of measuring high leaf chl contents without a saturation response is an important consideration for the practical use of chlorophyll meters.

Recurrent miscarriage: causes, evaluation and management.

Recurrent miscarriage is frustrating for the physician and a heartbreaking experience for the patient. Approximately 5% of couples trying to conceive have two consecutive miscarriages. Despite a thorough study of patients, the aetiology of this common obstetric complication is unknown in 50% of cases. Known causes include abnormal chromosomes, endocrinological disorders and uterine abnormalities. Although antiphospholipid antibodies have been demonstrated in miscarriages, the role played by alloimmune mechanisms remains unclear. New immunological approaches such as natural killer cells, regulatory T cells, tumour necrosis factor α, cell-derived microparticles, leptin, certain glycoproteins and cytokines should be considered. The management of thyroid diseases and immunological disorders is continuously evolving. Several genetic diagnostic procedures such as parental karyotyping and preimplantation genetic screening should probably not be used routinely. Antiphopholipid syndrome and some recurrent miscarriage-related endocrinological disorders can be effectively treated. Finally, new therapeutic approaches and the pleiotropic effects of old ones have led to improved fetal-maternal outcomes.

Current concepts and new trends in the diagnosis and management of recurrent miscarriage.

Pregnancy is a proinflammatory and hypercoagulable state. Miscarriage concerns approximately 15% of pregnancies. Recurrent miscarriage is a rather rare condition with an estimated incidence of 1% to 3%. However, despite years of investigation, the etiology is not established in up to 50% of cases. A multidisciplinary approach in the evaluation of miscarriage is essential to understand the cause and risk of recurrence. Although genetic factors are the major cause of spontaneous miscarriages, their relationship with recurrent miscarriage is less frequent. Recently, many kinds of genetic polymorphisms have also been found to be associated. Endocrine disorders such as poorly controlled diabetes, polycystic ovary syndrome, and hypothyroidism are linked with recurrent miscarriage. The relationship between recurrent miscarriage and subclinical thyroid disorders and thyroid autoimmunity is disputed, especially in early miscarriages. Uterine malformations should be considered as a cause of recurrent miscarriage. Although autoimmune-based recurrent miscarriage has been described, mainly antiphospholipid antibodies, the role of alloimmune mechanisms remains poorly understood. The influence of congenital thrombophilia is controversial. Antiphospholipid syndrome or antiphospholipid antibody-related recurrent miscarriage, and some endocrinologic disorders, have a specific and effective treatment. Still, the effectiveness of some common treatments needs to be demonstrated.

Índice de Charlson versus índice de Barthel como predictor de mortalidad e institucionalización en una unidad geriátrica de agudos y media estancia / Barthel and Charlson indexes for the prognosis of mortality and institutionalization in hospitalized geriatric patients

Introducción Comparar la validez del índice de Barthel (IB), el índice de comorbilidad de Charlson (ICC) y, una variante de este último, el índice de comorbilidad de Charlson corregido por la edad (ICCE) en el pronóstico de mortalidad e institucionalización en pacientes geriátricos hospitalizados.Material y métodos Se realiza un estudio retrospectivo de todos los pacientes ingresados durante el año 2006 en una unidad de agudos y media estancia de un servicio de geriatría (n=343). Como variables independientes se recogieron el IB al ingreso (registrado en la historia clínica de los pacientes) y el ICC e ICCE recogidos a posteriori con la información disponible. La variable resultado fue la ocurrencia de muerte o la institucionalización al alta del paciente, recogiéndose valores de sensibilidad y especificidad para cada uno de los puntos de corte seleccionados de las escalas evaluadas, y elaborando una curva ROC para cada una de ellas, calculando el área bajo la curva (ABC) con su intervalo de confianza (IC) del 95%. Resultados La muestra tenía una edad media de 82,3 años, con el 58,6% de mujeres. El ABC correspondiente al IB fue de 0,736 (IC del 95%=0,68–0,79), para el ICC fue de 0,61 (IC del 95%=0,55–0,67) y para el ICCE fue de 0,625 (IC del 95%=0,56–0,69), encontrándose diferencias estadísticamente significativas entre el ABC del IB frente al ABC de los otros dos índices (p<0,01).Conclusiones Como predictores de mortalidad e institucionalización, la validez del IB fue superior a la de los ICC (original y corregido por la edad). Por este motivo, el IB puede tener una mayor utilidad para el uso más adecuado de los recursos sanitarios disponibles(AU)

Introduction To compare the validity of the Barthel (BI) and Charlson comorbidity index (CCI) as well as the age-adjusted CCI for the prognosis of mortality and institutionalization in hospitalized geriatric patients.Material and methods A retrospective study was conducted to evaluate patients admitted to an acute care geriatric ward and mid-term care facility in 2006 (n=343). The independent variables were the admission BI (registered in the clinical history in all patients) and the CCI and the age-adjusted CCI, which were registered “a posteriori” using the available information. The outcome variable was mortality or institutionalization when the patient was discharged. The sensitivity and specificity values for each of the cut-off points selected from the scales analyzed were recorded and ROC curves were constructed for each of these points; the area under the curve (AUC) with a confidence interval (CI) of up to 95% was calculated.Results The mean age was 82.3 years (58.6% women). The AUC was 0.736 (95% CI=0.68–0.79) for the BI, 0.61 (95% CI=0.55–0.67) for the CCI and 0.625 (95% CI=0.56–0.69) for the age-adjusted CCI. Statistically significant differences were found among the AUC of the BI compared with that of the other two indexes (p<0.01).Conclusions As predictors of mortality and institutionalization, the BI was superior to the CCI and the age-adjusted CCI. The BI could therefore be more useful than the other two indexes when considering an adequate use of healthcare services (AU)

[Barthel and Charlson indexes for the prognosis of mortality and institutionalization in hospitalized geriatric patients]. / Indice de Charlson versus índice de Barthel como predictor de mortalidad e institucionalización en una unidad geriátrica de agudos y media estancia.

INTRODUCTION: To compare the validity of the Barthel (BI) and Charlson comorbidity index (CCI) as well as the age-adjusted CCI for the prognosis of mortality and institutionalization in hospitalized geriatric patients. MATERIAL AND METHODS: A retrospective study was conducted to evaluate patients admitted to an acute care geriatric ward and mid-term care facility in 2006 (n=343). The independent variables were the admission BI (registered in the clinical history in all patients) and the CCI and the age-adjusted CCI, which were registered "a posteriori" using the available information. The outcome variable was mortality or institutionalization when the patient was discharged. The sensitivity and specificity values for each of the cut-off points selected from the scales analyzed were recorded and ROC curves were constructed for each of these points; the area under the curve (AUC) with a confidence interval (CI) of up to 95% was calculated. RESULTS: The mean age was 82.3 years (58.6% women). The AUC was 0.736 (95% CI=0.68-0.79) for the BI, 0.61 (95% CI=0.55-0.67) for the CCI and 0.625 (95% CI=0.56-0.69) for the age-adjusted CCI. Statistically significant differences were found among the AUC of the BI compared with that of the other two indexes (p<0.01). CONCLUSIONS: As predictors of mortality and institutionalization, the BI was superior to the CCI and the age-adjusted CCI. The BI could therefore be more useful than the other two indexes when considering an adequate use of healthcare services.

Clinical implications and methodological challenges in the study of the neuropsychological correlates of cannabis, stimulant, and opioid abuse.

Chronic consumption of several drugs of abuse (cannabis, stimulants, opioids) has been associated with the presence of neuropsychological impairments in a broad range of functions. Nevertheless, in recent years neuropsychological research on substance abuse has focused on the study of impairments in the executive functions linked to the prefrontal cortex and their influence on the personality, cognitions, and behaviors of the substance abusers. The aim of our review is, first, to summarize the main neuropsychological impairments shown by classic studies, as well as these new discoveries in executive functioning; second, to consider the mediating role of neuropsychological status on treatment outcomes and analyze the impact of these impairments in clinical practice with drug addicts; and third, to review the principal methodological challenges associated with research in the field of the neuropsychology of substance abuse. We also highlight the convenience of intervening in those functions most relevant to the abusers' persistence in consumption and risk of relapse.