Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: Results from the Metocard-CNIC trial (Effect of Metoprolol in Cardioprotection during an Acute Myocardial Infarction)

The goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events. Early IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI). The METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up. Left ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval [CI]: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046). In patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction and ICD indications, and fewer heart failure admissions.

Early intravenous beta-blockers in patients with ST-segment elevation myocardial infarction before primary percutaneous coronary intervention

The impact of intravenous (IV) beta-blockers before primary percutaneous coronary intervention (PPCI) on infarct size and clinical outcomes is not well established. This study sought to conduct the first double-blind, placebo-controlled international multicenter study testing the effect of early IV beta-blockers before PPCI in a general ST-segment elevation myocardial infarction (STEMI) population. STEMI patients presenting <12 h from symptom onset in Killip class I to II without atrioventricular block were randomized 1:1 to IV metoprolol (2 × 5-mg bolus) or matched placebo before PPCI. Primary endpoint was myocardial infarct size as assessed by cardiac magnetic resonance imaging (CMR) at 30 days. Secondary endpoints were enzymatic infarct size and incidence of ventricular arrhythmias. Safety endpoints included symptomatic bradycardia, symptomatic hypotension, and cardiogenic shock. A total of 683 patients (mean age 62 ± 12 years; 75% male) were randomized to metoprolol (n = 336) or placebo (n = 346). CMR was performed in 342 patients (54.8%). Infarct size (percent of left ventricle [LV]) by CMR did not differ between the metoprolol (15.3 ± 11.0%) and placebo groups (14.9 ± 11.5%; p = 0.616). Peak and area under the creatine kinase curve did not differ between both groups. LV ejection fraction by CMR was 51.0 ± 10.9% in the metoprolol group and 51.6 ± 10.8% in the placebo group (p = 0.68). The incidence of malignant arrhythmias was 3.6% in the metoprolol group versus 6.9% in placebo (p = 0.050). The incidence of adverse events was not different between groups. In a nonrestricted STEMI population, early intravenous metoprolol before PPCI was not associated with a reduction in infarct size. Metoprolol reduced the incidence of malignant arrhythmias in the acute phase and was not associated with an increase in adverse events.

An Analysis of the Early Prediction of Highway Construction Project Completion using the Contract Status Report

History has shown that projects move in and out of poor status through the life of the project. Predicting the success or failure of a project to complete on time because of its recent history on the contract status report could provide our project managers another tool for monitoring contract progress. In many instances, poor contract progress results in the loss of contract time and late completion of projects. This research evaluates the combinations of work type, point in time physical work begins, recent poor status, and contract bid amount as indicators of late project completion.

Patterns in the space use of the Bearded Reedling, Panurus biarmicus, on the Tay Reedbeds, Scotland

This thesis presents research into the space use of a specialist reedbed Passerine, the Bearded Reedling, or Bearded Tit, Panurus biarmicus, with a view to inform the conservation of this species and reedbeds as a whole. How a species uses space, and how space use changes between individuals or over time, can influence: the ability to forage and hunt effectively, breeding success, susceptibility to predation, genetic health, disease spread, robustness against environmental change and ultimately, colonisation or extinction. Thus, understanding the space use of animals can provide critical insight into ecological systems. Birds offer interesting models when studying animal space use, as, by being intrinsically mobile, many bird species can occupy multiple spatial scales. As a consequence of being completely dependent on patchy and ephemeral reedbed habitats, the Bearded Reedling, has a clustered, inhomogeneous distribution throughout its range. This drives the existence of distinct spatial scales upon which space use studies should be characterised. Distribution and movement within a single reedbed can be considered local-scale, while spatial processes between reedbeds can be considered wide-scale. Temporal processes may act upon both of these scales. For example, changing interactions with predators may influence nest positioning at a local-scale, while seasonal changes in resource requirements might drive processes such as migration at a wide-scale. The Bearded Reedling has a wide temperate breeding range, extending over much of Eurasia. On the IUCN’s red list, it is listed as ‘of least concern’, with an estimated European population between 240,000-480,000 breeding pairs. Despite its relatively favourable conservation status, its dependence on reedbed habitats drives a fragmented distribution, with populations being concentrated in small, isolated, stands. Over the last century reedbed wetlands have suffered rapid declines caused by drainage schemes undertaken to improve land for development or agriculture. Additionally, many remaining reed stands are subject to extensive commercial management to produce thatch or biofuel. Conversely, in other areas, management is driven by conservation motives which recognise the present threats to reedbeds, and aim to encourage the diversity of species associated with these habitats. As the Bearded Reedling is fundamentally linked to the quality and structure of a reed stand, understanding the space use of this species will offer information for the direct conservation of this specialist species, and for the effects of reedbed management as a whole. This thesis first presents studies of space use at a local-scale. All local-scale research is conducted at the Tay Reedbeds in eastern Scotland. Mist netting and bird ringing data are used within capture recapture models, which include an explicit spatial component, to gain insight into the abundance of the Bearded Reedling on the Tay. This abundance estimation approach suggests the Tay reedbeds are a stronghold for this species on the British Isles, and that, as a high latitude site, the Tay may have importance for range expansion. A combination of transect surveys and radio-tracking data are then used to establish the local-scale space use of this species during the breeding and autumnal seasons. These data are related to changes in the structure of reed caused by local management in the form of mosaic winter reed cutting. Results suggest that birds exploit young and cut patches of reed as foraging resources when they are available, and that old, unmanaged reed is critical for nesting and winter foraging. Further local-scale studies concern the spatial patterns in the nesting habits of this species. Mosaic reed cutting creates clear edges in a reedbed. Artificial nests placed in the Tay Reedbeds demonstrate increased nest predation rates closer to the edges of cut patches. Additionally, high predation rates become reduced as the cut reed re-grows, suggesting that reed cutting may increase accessibility of the stand to predators. As Bearded Reedling nests are uncommon and difficult to locate, the timing, site selection and structure of a sample of real nests from the Tay is then detailed. These demonstrate an early, and relatively rigid breeding onset in this species, the importance of dense, compacted reeds as nesting sites and a degree of flexibility in nest structure. Conservation efforts will also benefit from studies into wide-scale spatial processes. These may be important when establishing how colonisation events occur and when predicting the effects of climatic change. The Bearded Reedling has been traditionally considered a resident species which only occasionally undertakes wide-scale, between-reedbed, movements. Indeed, the ecology of this species suggests strict year round local residency to reedbeds, with distinct seasonal changes in diet allowing occupation of these habitats year round. The European ringing recoveries of this species, since the 1970s are investigated to better characterise the wider movements of specialist resident. These suggest residency in southern populations, but higher instances of movement than expected in more northerly regions. In these regions wide-scale movement patterns resemble those of partial regular migratory species. An understanding of local and wide-scale spatial processes can offer a strong foundation on which to build conservation strategies. This thesis aims to use studies of space use to provide this foundation for the Bearded Reedling and offer further insight into the ecology of reedbed habitats as a whole. The thesis concludes by proposing an effective strategy for the conservation management of reedbeds that will especially benefit the Bearded Reedling.

Relación entre atrofia cortical difusa y desempeño cognitivo : estudio en población mayor de 60 años en un hospital universitario en la ciudad de Bogotá

El presente trabajo tuvo como objetivo evaluar la existencia de la relación entre la atrofia cortical difusa objetivada por neuroimagenes cerebrales y desempeños cognitivos determinados mediante la aplicación de pruebas neuropsicológicas que evalúan memoria de trabajo, razonamiento simbólico verbal y memoria anterógrada declarativa. Participaron 114 sujetos reclutados en el Hospital Universitario Mayor Méderi de la ciudad de Bogotá mediante muestreo de conveniencia. Los resultados arrojaron diferencias significativas entre los dos grupos (pacientes con diagnóstico de atrofia cortical difusa y pacientes con neuroimagenes interpretadas como dentro de los límites normales) en todas las pruebas neuropsicológicas aplicadas. Respecto a las variables demográficas se pudo observar que el grado de escolaridad contribuye como factor neuroprotector de un posible deterioro cognitivo. Tales hallazgos son importantes para determinar protocoles tempranos de detección de posible instalación de enfermedades neurodegenerativas primarias.

Early Carboniferous synorogenic basins evolution of the Ossa-Morena and

The stratigraphic record of the Early Carboniferous in Iberia reveals that synorogenic deposition was important and occurred simultaneously in basins influenced by extension and contraction with gravitational instability. In NW Iberia (Galicia – Trás-os-Montes Zone) contraction was dominant and the deposition took place in a forebulge outwards from the nappe stacking front. Here, synorogenic deposits were strongly affected by folding and thrusting as they were imbricated and incorporated in the allochthonous pile. In a different way, in SW Iberia (Ossa-Morena Zone) synorogenic deposition was influenced by extension and happened simultaneously with the onset of significant magmatism.

Late onset spinal cord ischemia after thoracoabdominal aortic aneurysm open repair

The aim of this study is to evaluate if spinal cord ischemia (SCI), especially its late presentation, and can be correlated to the results of intraoperative evoked potential monitoring (IOM). Methods. This study is a physician-initiated, retrospective, single-center, non-randomized study. Data from all patients undergoing a thoracoabdominal aortic aneurysm surgical repair (TAAA SR) between January 2016 and March 2020 IOM was collected and analyzed. Results. During the study period, 261 patients underwent TAAA SR with MEP/SSEPs monitoring [190 males, 73%; median age 65 (57-71)]. Thirty-seven patients suffered from SCI, for an overall rate of 14% (permanent 9%). When stratifying patients according to the SCI onset, 18 patients presented with an early (11 permanent) and 19 with a late SCI (<24h) (11 permanent). Of 261 patients undergoing TAAA SR with IOM, 15 were excluded due to changes in the upper extremity motor evoked potentials. For the remaining 246, the association between SCI and IOM was investigated: only irreversible IOM loss without peripheral changes have been found to be a risk factor for late onset SCI (p=.006). Furthermore, given that no statistical differences were found between the two groups when no IOM changes were recorded (p=.679), this situation cannot reliably rule out any SCI in our cohort. Independent risk factors for late spinal cord ischemia onset found at multivariate analysis were smoking history (p=.008), BMI>28 (p=.048) and TAAA extent II (p=.009). The irreversible MEP change without peripheral showed a trend of significance (p=.052). Conclusions. Evoked potential intraoperative monitoring is an important adjunct during thoracoabdominal aortic open repair to predict and possibly prevent spinal cord ischemia. Irreversible IOM loss without peripheral changes was predictive of late SCI, therefore more attention should be paid to the postoperative management of this subgroup of patients.

A prospective study on the early evaluation of response to androgen receptor-targeted agents with 11C-Choline, 68Ga-PSMA and 18F-FACBC PET in metastatic castration-resistant prostate cancer: a single center experience.

Background: The early identification of responsive and resistant patients to androgen-receptor targeting agents (ARTA) in metastatic castration resistant-prostate cancer (CRPC) is not completely possible with PSA assessment and conventional imaging. Considering its ability to determine metabolic activity of lesions, PET assessment might be a promising tool. Materials and methods: We performed a monocentric prospective study in patients with metastatic CRPC under treatment with ARTA to evaluate the role of different PET radiotracers: 49 patients were randomized to receive 11C-Choline, 18F-FACBC or 68Ga-PSMA PET, one scan before therapy onset and one two months later. The primary aim was to investigate the performance of three different novel PET radiotracers for the early evaluation of response to ARTA in metastatic CRPC patients; with regards to this aim, the outcome evaluated was biochemical response (PSA reduction ≥50%). The secondary aim was to investigate the prognostic role of several semiquantitative PET parameters and their variations with the different radiotracers in terms of biochemical PFS (bPFS) and overall survival (OS). The study was promoted by the Italian Department of Health (code RF-2016-02364809). Results: With regards to the primary endpoint, at univariate analysis a statistically significant correlation was found between MTV_VARIATION% (p=0.018) and TLA_VARIATION% (p=0.025) with 68Ga-PSMA PET and biochemical response. As for the secondary endpoints, significant correlations with bPFS were found for 68Ga-PSMA PET MTV_TOT_PET1 (p=0.001), TLA_TOT_PET1 (p=0.025), MTV_VARIATION% (p=0.031). For OS, statistically significant correlations were found for: MAJ_SUV_MAX_PET1 with 11C-Choline PET (p=0.007); MTV_TOT_PET1 (p=0.004), MAJ_SUV_MAX_PET1 (p=0.029), SUVMAX_VARIATION% (p=0.04), MTV_VARIATION% (p=0.015), TLA_VARIATION% (p=0.03) with 68Ga-PSMA PET,; MTV_TOT_PET1 (p=0.011), TLA_TOT_PET1 (p=0.009), MAJ_SUV_MAX_PET1 (p=0.027), MTV_VARIATION% (p=0.048) with 18F-FACBC. Conclusions: Our prospective study highlighted that several 68Ga-PSMA and 18F-FACBC semiquantitative PET parameters and their variations present a prognostic value in terms of OS and bPFS and a correlation with biochemical response, that could help to assess response to ARTA.

Fractalkine (cx3cl1) Is Involved In The Early Activation Of Hypothalamic Inflammation In Experimental Obesity.

Hypothalamic inflammation is a common feature of experimental obesity. Dietary fats are important triggers of this process, inducing the activation of toll-like receptor-4 (TLR4) signaling and endoplasmic reticulum stress. Microglia cells, which are the cellular components of the innate immune system in the brain, are expected to play a role in the early activation of diet-induced hypothalamic inflammation. Here, we use bone marrow transplants to generate mice chimeras that express a functional TLR4 in the entire body except in bone marrow-derived cells or only in bone marrow-derived cells. We show that a functional TLR4 in bone marrow-derived cells is required for the complete expression of the diet-induced obese phenotype and for the perpetuation of inflammation in the hypothalamus. In an obesity-prone mouse strain, the chemokine CX3CL1 (fractalkine) is rapidly induced in the neurons of the hypothalamus after the introduction of a high-fat diet. The inhibition of hypothalamic fractalkine reduces diet-induced hypothalamic inflammation and the recruitment of bone marrow-derived monocytic cells to the hypothalamus; in addition, this inhibition reduces obesity and protects against diet-induced glucose intolerance. Thus, fractalkine is an important player in the early induction of diet-induced hypothalamic inflammation, and its inhibition impairs the induction of the obese and glucose intolerance phenotypes.

Neonatal Outcomes Of Late Preterm And Early Term Birth.

To compare neonatal deaths and complications in infants born at 34-36 weeks and six days (late preterm: LPT) with those born at term (37-41 weeks and six days); to compare deaths of early term (37-38 weeks) versus late term (39-41 weeks and six days) infants; to search for any temporal trend in LPT rate. A retrospective cohort study of live births was conducted in the Campinas State University, Brazil, from January 2004 to December 2010. Multiple pregnancies, malformations and congenital diseases were excluded. Control for confounders was performed. The level of significance was set at p<0.05. After exclusions, there were 17,988 births (1653 late preterm and 16,345 term infants). A higher mortality in LPT versus term was observed, with an adjusted odds ratio (OR) of 5.29 (p<0.0001). Most complications were significantly associated with LPT births. There was a significant increase in LPT rate throughout the study period, but no significant trend in the rate of medically indicated deliveries. A higher mortality was observed in early term versus late term infants, with adjusted OR: 2.43 (p=0.038). LPT and early term infants have a significantly higher risk of death.

Newborn Hearing Screening And Early Diagnostic In The Nicu.

The aim was to describe the outcome of neonatal hearing screening (NHS) and audiological diagnosis in neonates in the NICU. The sample was divided into Group I: neonates who underwent NHS in one step and Group II: neonates who underwent a test and retest NHS. NHS procedure was automated auditory brainstem response. NHS was performed in 82.1% of surviving neonates. For GI, referral rate was 18.6% and false-positive was 62.2% (normal hearing in the diagnostic stage). In GII, with retest, referral rate dropped to 4.1% and false-positive to 12.5%. Sensorineural hearing loss was found in 13.2% of infants and conductive in 26.4% of cases. There was one case of auditory neuropathy spectrum (1.9%). Dropout rate in whole process was 21.7% for GI and 24.03% for GII. We concluded that it was not possible to perform universal NHS in the studied sample or, in many cases, to apply it within the first month of life. Retest reduced failure and false-positive rate and did not increase evasion, indicating that it is a recommendable step in NHS programs in the NICU. The incidence of hearing loss was 2.9%, considering sensorineural hearing loss (0.91%), conductive (1.83%) and auditory neuropathy spectrum (0.19%).

Hypothermia And Early Neonatal Mortality In Preterm Infants.

To evaluate intervention practices associated with hypothermia at both 5 minutes after birth and at neonatal intensive care unit (NICU) admission and to determine whether hypothermia at NICU admission is associated with early neonatal death in preterm infants. This prospective cohort included 1764 inborn neonates of 22-33 weeks without malformations admitted to 9 university NICUs from August 2010 through April 2012. All centers followed neonatal International Liaison Committee on Resuscitation recommendations for the stabilization and resuscitation in the delivery room (DR). Variables associated with hypothermia (axillary temperature <36.0 °C) 5 minutes after birth and at NICU admission, as well as those associated with early death, were analyzed by logistic regression. Hypothermia 5 minutes after birth and at NICU admission was noted in 44% and 51%, respectively, with 6% of early neonatal deaths. Adjusted for confounding variables, practices associated with hypothermia at 5 minutes after birth were DR temperature <25 °C (OR 2.13, 95% CI 1.67-2.28), maternal temperature at delivery <36.0 °C (OR 1.93, 95% CI 1.49-2.51), and use of plastic bag/wrap (OR 0.53, 95% CI 0.40-0.70). The variables associated with hypothermia at NICU admission were DR temperature <25 °C (OR 1.44, 95% CI 1.10-1.88), respiratory support with cold air in the DR (OR 1.40, 95% CI 1.03-1.88) and during transport to NICU (OR 1.51, 95% CI 1.08-2.13), and cap use (OR 0.55, 95% CI 0.39-0.78). Hypothermia at NICU admission increased the chance of early neonatal death by 1.64-fold (95% CI 1.03-2.61). Simple interventions, such as maintaining DR temperature >25 °C, reducing maternal hypothermia prior to delivery, providing plastic bags/wraps and caps for the newly born infants, and using warm resuscitation gases, may decrease hypothermia at NICU admission and improve early neonatal survival.

Oxidative Stress And Susceptibility To Mitochondrial Permeability Transition Precedes The Onset Of Diabetes In Autoimmune Non-obese Diabetic Mice.

Beta cell destruction in type 1 diabetes (TID) is associated with cellular oxidative stress and mitochondrial pathway of cell death. The aim of this study was to determine whether oxidative stress and mitochondrial dysfunction are present in T1D model (non-obese diabetic mouse, NOD) and if they are related to the stages of disease development. NOD mice were studied at three stages: non-diabetic, pre-diabetic, and diabetic and compared with age-matched Balb/c mice. Mitochondria respiration rates measured at phosphorylating and resting states in liver and soleus biopsies and in isolated liver mitochondria were similar in NOD and Balb/c mice at the three disease stages. However, NOD liver mitochondria were more susceptible to calcium-induced mitochondrial permeability transition as determined by cyclosporine-A-sensitive swelling and by decreased calcium retention capacity in all three stages of diabetes development. Mitochondria H2O2 production rate was higher in non-diabetic, but unaltered in pre-diabetic and diabetic NOD mice. The global cell reactive oxygen species (ROS), but not specific mitochondria ROS production, was significantly increased in NOD lymphomononuclear and stem cells in all disease stages. In addition, marked elevated rates of 2',7'-dichlorodihydrofluorescein (H2DCF) oxidation were observed in pancreatic islets from non-diabetic NOD mice. Using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) and lipidomic approach, we identified oxidized lipid markers in NOD liver mitochondria for each disease stage, most of them being derivatives of diacylglycerols and phospholipids. These results suggest that the cellular oxidative stress precedes the establishment of diabetes and may be the cause of mitochondrial dysfunction that is involved in beta cell death.

Factors Associated With The Onset Of Hypertension In Women Of 50 Years Of Age Or More In A City In Southeastern Brazil.

To evaluate factors associated with hypertension in Brazilian women of 50 years of age or more. A cross-sectional population based study using self-reports. A total of 622 women were included. The association between sociodemographic, clinical and behavioral factors and the woman's age at the onset of hypertension was evaluated. Data were analyzed according to cumulative continuation rates without hypertension, using the life-table method and considering annual intervals. Next, a Cox multiple regression analysis model was adjusted to analyze the occurrence rates of hypertension according to various predictor variables. Significance level was pre-established at 5% (95% confidence level) and the sampling plan (primary sampling unit) was taken into consideration. Median age at onset of hypertension was 64.3 years. Cumulative continuation rate without hypertension at 90 years was 20%. Higher body mass index (BMI) at 20-30 years of age was associated with a higher cumulative occurrence rate of hypertension over time (coefficient=0.078; p<0.001). Being white was associated with a lower cumulative occurrence rate of hypertension over time (coefficient= -0.439; p=0.003), while smoking >15 cigarettes/day was associated with a higher rate over time (coefficient=0.485; p=0.004). The results of the present study highlight the importance of weight control in young adulthood and of avoiding smoking in preventing hypertension in women aged ≥50 years.

Factors Associated With The Age Of The Onset Of Diabetes In Women Aged 50 years Or More: A Population-based Study.

Investigate factors associated with the onset of diabetes in women aged more than 49 years. Cross-sectional, population-based study using self-reports with 622 women. The dependent variable was the age of occurrence of diabetes using the life table method. Cox multiple regression models were adjusted to analyse the onset of diabetes according to predictor variables. Sociodemographic, clinical and behavioural factors were evaluated. Of the 622 women interviewed, 22.7% had diabetes. The mean age at onset was 56 years. The factors associated with the age of occurrence of diabetes were self-rated health (very good, good) (coefficient=-0.792; SE of the coefficient=0.215; p=0.0001), more than two individuals living in the household (coefficient=0.656, SE of the coefficient=0.223; p=0.003), and body mass index (BMI) (kg/m(2)) at 20-30 years of age (coefficient= 0.056, SE of the coefficient=0.023; p=0.014). Self-rated health considered good or very good was associated with a higher rate of survival without diabetes. Sharing a home with two or more other people and a weight increase at 20-30 years of age was associated with the onset of type 2 diabetes.