Do we need another heart failure biomarker. focus on soluble suppression of tumorigenicity 2 (sST2)

If sST2 indeed turns into the HbA1c of heart failure, its value should increase exponentially in our management of patients with heart failure. Serial sST2 levels should allow us to titrate therapy and monitor the clinical state of the patient. In addition, since sST2 is such a strong marker of the risk of death, it would not be surprising to see a level be used to make decisions when patients are on the cusp of such therapies as ICD, CRT, CardioMems implantation and even left ventricular assist devices. A discussion about the use of biomarkers would not be complete without mentioning the issue of surrogates for determining the therapy effectiveness of some of the newer heart failure drugs. Novartis’s EntrestoVR , the brand name for its recently CE marked and FDA approved ARNI1 drug (previously known as LCZ696) and Servier’s ivabradine drug CorlanorVR (marketed by Amgen in the USA), also CE marked and FDA approved, while offering exciting potential benefits to heart failure patients—even being hailed ‘game-changer’ drugs by some—raises the thorny issue of cost vs. benefit. These new drugs are several times the cost of the generics that have become the mainstay of heart failure treatment, i.e. ACE inhibitors, angiotensin receptor blocker (ARBs), beta-blockers, etc. Pushback is therefore expected from payers. Because sST2 changes rapidly with the underlying condition of the patient, is not affected by normal confounding factors, and has a single cut point, it may be ideally suited to help clinicians determine if these newer mediations are effective for each patient, are improving quality of life, and whether dosing needs to be titrated or changed. The new reality of heart failure care is that while more treatment options have opened up, which can literally be a lifesaver for millions of patients, the burden on healthcare systems has skyrocketed. Biomarkers, and particularly sST2, could offer physicians and payers a way to bring treatment down to an individual patient level, providing

Circulating Biologically Active Adrenomedullin Predicts Organ Failure and Mortality in Sepsis

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Biologically active adrenomedullin (bio-ADM) is an emerging biomarker for sepsis. We explored whether bio-ADM concentration could predict severity, organ failure, and 30-day mortality in septic patients. METHODS: In 215 septic patients (109 patients with sepsis; 106 patients with septic shock), bio-ADM concentration was measured at diagnosis of sepsis, using sphingotest bio-ADM (Sphingotec GmbH, Hennigsdorf, Germany) and analyzed in terms of sepsis severity, vasopressor use, and 30-day mortality. The number of organ failures, sequential (sepsis-related) organ failure assessment (SOFA) score, and 30-day mortality were compared according to bio-ADM quartiles. RESULTS: Bio-ADM concentration was significantly higher in patients with septic shock, vasopressor use, and non-survivors than in patients with solitary sepsis, no vasopressor use, and survivors, respectively (all P<0.0001). Bio-ADM quartiles were associated with the number of organ failures (P<0.0001), as well as SOFA cardiovascular, renal, coagulation, and liver subscores (all P<0.05). The 30-day mortality rate showed a stepwise increase in each bio-ADM quartile (all P<0.0001). Bio-ADM concentration and SOFA score equally predicted the 30-day mortality (area under the curve: 0.827 vs 0.830). CONCLUSIONS: Bio-ADM could serve as a useful and objective biomarker to predict severity, organ failure, and 30-day mortality in septic patients

ST2 and Multimarker Testing in Acute Decompensated Heart Failure

Most data on heart failure biomarkers have been derived from patient cohorts with chronic disease. However, risk prediction in patients admitted with acute decompensated heart failure (ADHF) remains a challenge. ADHF is not a single disease: it presents in various manners, and different causes may underlie ADHF, which may be reflected by different biomarkers. Soluble suppression of tumorigenicity 2 (ST2) has been shown to be a strong independent predictor of short-, mid-, and long-term outcome in ADHF. Furthermore, combining biomarkers may help further improve the prognostic power of ST2. The ProBNP Investigation of Dyspnea in the Emergency Department study showed that elevated plasma levels of ST2 together with elevated levels of 4 other biomarkers have clear incremental values to predict outcome in ADHF. The Multinational Observational Cohort on Acute Heart Failure study is an international collaborative network that recruited 5,306 patients hospitalized for ADHF that demonstrated that ST2 and midregional pro-adrenomedulin had independently strong value to predict 30-day and 1-year outcome in patients with ADHF. The Multinational Observational Cohort on Acute Heart Failure study also showed that C-reactive protein plus ST2 better classified risk in patients with ADHFs than ST2 alone. Combining biomarkers for risk prediction or risk stratification might have clinical and more importantly pathophysiological meaning

3D and 4D Simulations for Landscape Reconstruction and Damage Scenarios. GIS Pilot Applications

The project 3D and 4D Simulations for Landscape Reconstruction and Damage Scenarios: GIS Pilot Applications has been devised with the intention to deal with the demand for research, innovation and applicative methodology on the part of the international programme, requiring concrete results to increase the capacity to know, anticipate and respond to a natural disaster. This project therefore sets out to develop an experimental methodology, a wide geodatabase, a connected performant GIS platform and multifunctional scenarios able to profitably relate the added values deriving from different geotechnologies, aimed at a series of crucial steps regarding landscape reconstruction, event simulation, damage evaluation, emergency management, multi-temporal analysis. The Vesuvius area has been chosen for the pilot application owing to such an impressive number of people and buildings subject to volcanic risk that one could speak in terms of a possible national disaster. The steps of the project move around the following core elements: creation of models that reproduce the territorial and anthropic structure of the past periods, and reconstruction of the urbanized area, with temporal distinctions; three-dimensional representation of the Vesuvius area in terms of infrastructuralresidential aspects; GIS simulation of the expected event; first examination of the healthcareepidemiological consequences; educational proposals. This paper represents a proactive contribution which describes the aims of the project, the steps which constitute a set of specific procedures for the methodology which we are experimenting, and some thoughts regarding the geodatabase useful to “package” illustrative elaborations. Since the involvement of the population and adequate hazard preparedness are very important aspects, some educational and communicational considerations are presented in connection with the use of geotechnologies to promote the knowledge of risk

A lead isotope perspective on urban development in ancient Naples

The influence of a sophisticated water distribution system on urban development in Roman times is tested against the impact of Vesuvius volcanic activity, in particular the great eruption of AD 79, on all of the ancient cities of the Bay of Naples (Neapolis). Written accounts on urbanization outside of Rome are scarce and the archaeological record sketchy, especially during the tumultuous fifth and sixth centuries AD when Neapolis became the dominant city in the region. Here we show that isotopic ratios of lead measured on a well-dated sedimentary sequence from Neapolis’ harbor covering the first six centuries CE have recorded how the AD 79 eruption was followed by a complete overhaul of Neapolis’ water supply network. The Pb isotopic signatures of the sediments further reveal that the previously steady growth of Neapolis’ water distribution system ceased during the collapse of the fifth century AD, although vital repairs to this critical infrastructure were still carried out in the aftermath of invasions and volcanic eruptions

A multidisciplinary study of an exceptional prehistoric waste dump in the mountainous inland of Calabria (Italy) : implications for reconstructions of prehistoric land use and vegetation in Southern Italy

The mountainous inland of northern Calabria (Southern Italy) is known for its sparse prehistoric human occupation. Nevertheless, a thorough multidisciplinary approach of field walking, geophysical survey and invasive research led to the discovery of a major archaeological archive. This archive concerns a rich multi-phased dump, spanning about 3000 years (Late Neolithic to Late Imperial Roman Age) and holding two Somma-Vesuvius tephra. Of these, the younger is a distinct layer of juvenile tephra from the Pompeii eruption, while the older concerns reworked tephra from the Bronze Age AP2 eruption (ca. 1700 cal. yr BP). The large dump contains abundant ceramics, faunal remains and charcoal, and most probably originated through long-continued deposition of waste in a former gully like system of depressions. This resulted in an inversed, mound-like relief, whose anthropogenic origin had not been recognized in earlier research. The tephras were found to be important markers that support the reconstruction of the occupational history of the site. The sequence of occupational phases is very similar to that observed in a recent palaeoecological study from nearby situated former lakes (Lago Forano/Fontana Manca). This suggests that this sequence reflects the more regional occupational history of Calabria, which goes back to ca. 3000 BC. Attention is paid to the potential link between this history and Holocene climatic phases, for which no indication was found. The history deviates strongly from histories deduced from the few, but major palaeorecords elsewhere in the inlands of Southern Italy (Lago Grande di Monticchio and Lago Trifoglietti). We conclude that major regional variation occurred in prehistoric land use and its impacts on the vegetation cover of Southern Italy, and studies of additional palaeoarchives are needed to unravel this complex history. Finally, shortcomings of archaeological predictive models are discussed and the advantages of truly integrated multidisciplinary research

Multiphase procedure for landscape reconstruction and their evolution analysis. GIS modelling for areas exposed to high volcanic risk

This paper – focussed on the province of Naples, where many municipalities with a huge demographic and building density are subject to high volcanic risk owing to the presence of the Campi Flegrei (Phlegrean Fields) caldera and the Somma-Vesuvius complex – highlights the methodological-applicative steps leading to the setting up of a multiphase procedure for landscape reconstruction and their evolution analysis. From the operational point of view, the research led to the: (1) digitalisation, georeferencing and comparison of cartographies of different periods of time and recent satellite images; (2) elaboration and publication of a multilayer Story Map; (3) accurate vectorisation of the data of the buildings, for each period of time considered, and the use of kernel density in 2D and 3D; (4) application of the extrusion techniques to the physical aspects and anthropic structures; (5) production of 4D animations and film clips for each period of time considered. A procedure is thus tested made up of preparatory sequences, leading to a GIS modelling aimed at highlighting and quantifying significant problem areas and high exposure situations and at reconstructing the phases which in time have brought about an intense and widespread growth process of the artificial surfaces, considerably altering the features of the landscape and noticeably showing up the risk values. In a context characterised by land use conflicts and anomalous conditions of anthropic congestion, a diagnostic approach through images in 2D, 3D and 4D is used, with the aim to support the prevention and planning of emergencies, process damage scenarios and identify the main intervention orders, raise awareness and educate to risk, making an impact on the collective imagination through the enhancement of specific geotechnological functionalities of great didactic interest

Imaging polar and dipolar sources of geophysical anomalies by probability tomography. Part II: Application to the Vesuvius volcanic area

In the previous part I, we have developed the generalized theory of the probability tomography method to image polar and dipolar sources of a vector or scalar geophysical anomaly field. The purpose of the new method was to improve the core-and-boundary resolution of the most probable buried sources of the anomalies detected in a datum domain. In this paper, which constitutes the part II of the same study, an application of the new approach to the Vesuvius volcano (Naples, Italy) is illustrated in detail by analyzing geoelectrical, self-potential and gravity datasets collected over the whole volcanic area. The purpose is to get new insights into the shallow structure and hydrothermal system of Vesuvius, and the deep geometry of the tectonic depression within which the volcano grew.Comment: 7 pages, 10 figure

The interpretation of brain natriuretic peptide in critical care patients; will it ever be useful?

The measurement of B-type natriuretic peptide (BNP) is recommended for the diagnosis of decompensated heart failure, the prognosis of chronic heart failure is worse if BNP is increased and studies suggest that BNP is useful to guide therapy. A study by Di Somma and colleagues adds to the body of evidence showing that patients with a marked decrease in BNP concentrations during their hospital admission are less likely to be readmitted with a further adverse cardiac event than patients in whom BNP fails to decrease. However, the wider interpretation of BNP concentrations in critically ill patients with other conditions remains uncertain

Splicing factors Sf3A2 and Prp31 have direct roles in mitotic chromosome segregation

Several studies have shown that RNAi-mediated depletion of splicing factors (SFs) results in mitotic abnormalities. However, it is currently unclear whether these abnormalities reflect defective splicing of specific pre-mRNAs or a direct role of the SFs in mitosis. Here, we show that two highly conserved SFs, Sf3A2 and Prp31, are required for chromosome segregation in both Drosophila and human cells. Injections of anti-Sf3A2 and anti-Prp31 antibodies into Drosophila embryos disrupt mitotic division within 1 min, arguing strongly against a splicing-related mitotic function of these factors. We demonstrate that both SFs bind spindle microtubules (MTs) and the Ndc80 complex, which in Sf3A2- and Prp31-depleted cells is not tightly associated with the kinetochores; in HeLa cells the Ndc80/HEC1-SF interaction is restricted to the M phase. These results indicate that Sf3A2 and Prp31 directly regulate interactions among kinetochores, spindle microtubules and the Ndc80 complex in both Drosophila and human cells