Echocardiographic evaluation of right ventricular diastolic function in pulmonary hypertension

Background: Right ventricular (RV) diastolic dysfunction may be prognostic in pulmonary hypertension (PH). However, its assessment is complex and relies on conductance catheterisation. We aimed to evaluate echocardiography-based parameters as surrogates of RV diastolic function, provide validation against the gold standard, end-diastolic elastance (Eed), and define the prognostic impact of echocardiography-derived RV diastolic dysfunction. Methods: Patients with suspected PH who underwent right heart catheterisation including conductance catheterisation were prospectively recruited. In this study population, an echocardiography-based RV diastolic function surrogate was derived. Survival analyses were performed in patients with precapillary PH in the Giessen PH Registry, with external validation in patients with pulmonary arterial hypertension at Sapienza University (Rome). Results: In the derivation cohort (n=61), the early/late diastolic tricuspid inflow velocity ratio (E/A) and early tricuspid inflow velocity/early diastolic tricuspid annular velocity ratio (E/e') did not correlate with Eed (p>0.05). Receiver operating characteristic analysis revealed a large area under the curve (AUC) for the peak lateral tricuspid annulus systolic velocity/right atrial area index ratio (S'/RAAi) to detect elevated Eed (AUC 0.913, 95% confidence interval (CI) 0.839-0.986) and elevated end-diastolic pressure (AUC 0.848, 95% CI 0.699-0.998) with an optimal threshold of 0.81 m2·s-1·cm-1. Subgroup analyses demonstrated a large AUC in patients with preserved RV systolic function (AUC 0.963, 95% CI 0.882-1.000). Survival analyses confirmed the prognostic relevance of S'/RAAi in the Giessen PH Registry (n=225) and the external validation cohort (n=106). Conclusions: Our study demonstrates the usefulness of echocardiography-derived S'/RAAi for noninvasive assessment of RV diastolic function and prognosis in PH

Reconfigurable self-assembly through chiral control of interfacial tension

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 481 (2012): 348–351, doi:10.1038/nature10769.From determining optical properties of simple molecular crystals to establishing preferred handedness in highly complex vertebrates, molecular chirality profoundly influences the structural, mechanical, and optical properties of both synthetic and biological matter at macroscopic lengthscales1,2. In soft materials such as amphiphilic lipids and liquid crystals, the competition between local chiral interactions and global constraints imposed by the geometry of the self-assembled structures leads to frustration and the assembly of unique materials3-6. An example of particular interest is smectic liquid crystals, where the 2D layered geometry cannot support twist, expelling chirality to the edges in a manner analogous to the expulsion of a magnetic field from superconductors7-10. Here, we demonstrate a previously unexplored consequence of this geometric frustration which leads to a new design principle for the assembly of chiral molecules. Using a model system of colloidal membranes11, we show that molecular chirality can control the interfacial tension, an important property of multi-component mixtures. This finding suggests an analogy between chiral twist which is expelled to the edge of 2D membranes, and amphiphilic surfactants which are expelled to oil-water interfaces12. Similar to surfactants, chiral control of interfacial tension drives the assembly of myriad polymorphic assemblages such as twisted ribbons with linear and circular topologies, starfish membranes, and double and triple helices. Tuning molecular chirality in situ enables dynamical control of line tension that powers polymorphic transitions between various chiral structures. These findings outline a general strategy for the assembly of reconfigurable chiral materials which can easily be moved, stretched, attached to one another, and transformed between multiple conformational states, thus enabling precise assembly and nano-sculpting of highly dynamical and designable materials with complex topologies.This work was supported by the National Science Foundation (NSF-MRSEC-0820492, NSF-DMR-0955776, NSF-MRI 0923057) and Petroleum Research Fund (ACS-PRF 50558-DNI7).2012-07-0

Influence of anemia on outcomes of hospitalized COVID-19 patients

Covid-19 infektivna je bolest uzrokovana koronavirusom teškog akutnog respiratornog sindroma 2 (SARS-CoV-2). U težim oblicima bolesti, ljudi starije životne dobi, imunokompromitirani i pacijenti opterećeni komorbiditetima često zahtijevaju hospitalizaciju. Anemija je stanje u kojemu krv ima smanjenu mogućnost prenošenja kisika u tkiva te može utjecati na tijek liječenja i preživljenje pacijenata kod COVID-19 bolesti. Cilj ovog rada je istražiti povezanosti kliničkih ishoda liječenja s prisustvom anemije prilikom hospitalizacije kod pacijenata zaraženih virusom SARS-Cov 2 u tercijarnom centru KB Dubrava. Rađena je usporedba laboratorijskih, anamnestičkih i demografskih parametara te broja komplikacija među grupama sa i bez anemije na podatcima od 5872 pacijenata. Pacijenti s anemijom imali su značajne razlike u većini mjerenih laboratorijskih parametara i veće opterećenje komorbiditetima. Prisutnost anemije je bila povećana s većom vjerojatnosti pojave venske tromboembolije, velikog krvarenja i smrti tijekom hospitalizacije. Anemija je značajan negativan prediktivni čimbenik preživljenja pacijenata prilikom hospitalizacije zbog COVID-19 bolesti.Covid-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In more severe forms of the disease, elderly, immunocompromised and patients with comorbidities often require hospitalization. Anemia is a condition in which the blood has a reduced ability to transfer oxygen to the tissues, and may affect the survival of patients with COVID-19 disease. The aim of this paper is to investigate the relationship between clinical treatment outcomes and the presence of anemia during hospitalization in patients infected with the SARS-Cov 2 virus in the tertiary center of KB Dubrava. A comparison of laboratory, anamnestic and demographic parameters and the number of complications between the groups with and without anemia was made on the basis of data from 5872 patients. Patients with anemia had significant differences in most of the measured laboratory parameters and a higher burden of comorbidities. They had higher frequency of venous thromboembolism, major bleeding and death during hospitalization. Anemia is a significant negative predictive factor of patient survival during hospitalization due to COVID-19 disease

Influence of anemia on outcomes of hospitalized COVID-19 patients

Covid-19 infektivna je bolest uzrokovana koronavirusom teškog akutnog respiratornog sindroma 2 (SARS-CoV-2). U težim oblicima bolesti, ljudi starije životne dobi, imunokompromitirani i pacijenti opterećeni komorbiditetima često zahtijevaju hospitalizaciju. Anemija je stanje u kojemu krv ima smanjenu mogućnost prenošenja kisika u tkiva te može utjecati na tijek liječenja i preživljenje pacijenata kod COVID-19 bolesti. Cilj ovog rada je istražiti povezanosti kliničkih ishoda liječenja s prisustvom anemije prilikom hospitalizacije kod pacijenata zaraženih virusom SARS-Cov 2 u tercijarnom centru KB Dubrava. Rađena je usporedba laboratorijskih, anamnestičkih i demografskih parametara te broja komplikacija među grupama sa i bez anemije na podatcima od 5872 pacijenata. Pacijenti s anemijom imali su značajne razlike u većini mjerenih laboratorijskih parametara i veće opterećenje komorbiditetima. Prisutnost anemije je bila povećana s većom vjerojatnosti pojave venske tromboembolije, velikog krvarenja i smrti tijekom hospitalizacije. Anemija je značajan negativan prediktivni čimbenik preživljenja pacijenata prilikom hospitalizacije zbog COVID-19 bolesti.Covid-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In more severe forms of the disease, elderly, immunocompromised and patients with comorbidities often require hospitalization. Anemia is a condition in which the blood has a reduced ability to transfer oxygen to the tissues, and may affect the survival of patients with COVID-19 disease. The aim of this paper is to investigate the relationship between clinical treatment outcomes and the presence of anemia during hospitalization in patients infected with the SARS-Cov 2 virus in the tertiary center of KB Dubrava. A comparison of laboratory, anamnestic and demographic parameters and the number of complications between the groups with and without anemia was made on the basis of data from 5872 patients. Patients with anemia had significant differences in most of the measured laboratory parameters and a higher burden of comorbidities. They had higher frequency of venous thromboembolism, major bleeding and death during hospitalization. Anemia is a significant negative predictive factor of patient survival during hospitalization due to COVID-19 disease

Effect of Zeolite Catalyst on the Pyrolysis Kinetics of Multi-Layered Plastic Food Packaging

Pyrolysis is gaining more significance as a technology used to produce alternative fuels and chemicals. This study dealt with the catalytic pyrolysis of a realistic waste mixture of multi-layered plastic food packaging. The thermal behavior, kinetic parameters, and kinetic model of multi-layered plastic food packaging pyrolysis were determined to show its potential for process scale-up. In particular, we aimed to evaluate the effect of a ZSM-5 zeolite catalyst, modified with iron(III) oxide. The pyrolysis process on this decagonal structure was investigated using thermogravimetric analysis under nitrogen flow at four heating rates ranging between 40 and 600 °C. The kinetic study was conducted using the model-free isoconversional Friedman method as well as advanced statistical analysis to determine the reaction mechanism of the process. The thermal decomposition occurred in the range of 350–510 °C, with a mass loss greater than 90%. The kinetic study revealed a complex pyrolysis process, which consisted of three decomposition stages, diffusion, and Avrami-Erofeev reaction types. The activation energy values determined by the Friedman method rose with the degree of conversion, from 127 kJ mol−1 at 0.01 to 219 kJ mol−1 at 0.95. The doping of the catalyst lowered the activation energy of the reaction by 44% and 8% in the first and second stages, respectively, and increased the acidity of the zeolites, thus enhancing the reactivity on the surface of the catalysts. Lower activation energy meant less energy was required to heat the pyrolysis reactor since the onset temperature of sample decomposition was reduced

Secondary polycythemia in acutely ill COVID-19 patients is associated with higher mortality but not markedly higher thrombotic risk

Secondary polycythemia is commonly observed among patients with chronic pulmonary diseases. However, its significance in the context of Coronavirus disease 2019 (COVID-19) is unknown. We retrospectively evaluated a total of 5872 hospitalized COVID-19 patients with mostly severe and critical symptoms, and without prior or subsequently diagnosed myeloproliferative neoplasm. Patients were stratified based on admission hemoglobin into four subgroups: anemia (hemoglobin 165 g/L for females and >185 g/L for males). Among 5872 patients, a total of 158 (2.7%) had mild and 25 (0.4%) severe polycythemia. Polycythemia was significantly associated with higher respiratory and functional impairment, reduced plasma volume, higher serum osmolarity and comorbidity burden specific to the degree of polycythemia. Patients presenting with mild (odds ratio (OR) = 1.63, p = .003) and severe polycythemia (OR = 4.98, p < .001) had increased risk of death in comparison to patients with normal hemoglobin, whereas no significant associations with venous thromboembolism, arterial thrombosis nor major bleeding were observed. Anemia was associated with higher risk of death (OR = 1.42, p < .001), venous thromboembolism (OR = 1.34, p < .006) and major bleeding (OR = 2.27, p < .001) in comparison to normal hemoglobin. Associations of polycythemia and anemia with mortality diminished, and anemia with venous thromboembolism and major bleeding persisted, after multivariate adjustments for age, sex, comorbidities, COVID-19 severity and functional status. Secondary polycythemia in hospitalized COVID-19 patients without prior of subsequently diagnosed myeloproliferative neoplasm is rare and is associated with high mortality, increasing with degree of polycythemia, but not markedly higher thrombotic ris

Clinical Relevance of Right Atrial Functional Response to Treatment in Pulmonary Arterial Hypertension

Background: Right atrial (RA) function has emerged as an important determinant of outcome in pulmonary arterial hypertension (PAH). However, studies exploring RA function after initiation of specific pulmonary vascular treatment and its association with outcome in patients with incident PAH are lacking.Methods: RA peak longitudinal strain (PLS), passive strain (PS), and peak active contraction strain (PACS) were retrospectively assessed in 56 treatment-naive patients with PAH at baseline and during follow-up after initiation of specific monotherapy or combination therapy. Patients were grouped according to their individual RA functional response to treatment, based on change from baseline (Delta): worsened (first Delta-tertile), stable (second Delta-tertile), and improved (third Delta-tertile). The Spearman's rho correlation and linear regression analysis were used to determine associations. Time to clinical worsening (defined as deterioration of functional class or 6-min walking distance, disease-related hospital admission, or death) was measured from the follow-up assessment. The association of RA functional treatment response with time to clinical worsening was assessed using the Kaplan-Meier and the Cox regression analyses.Results: Median (interquartile range) time to echocardiographic follow-up was 11 (9-12) months. Of the 56 patients, 37 patients (66%) received specific dual or triple combination therapy. Delta RA PLS during follow-up was significantly associated with changes in key hemodynamic and echocardiographic parameters. The change of pulmonary vascular resistance, right ventricular (RV) end-systolic area, and global longitudinal strain were independently associated with Delta RA PLS. The median time to clinical worsening after echocardiographic follow-up was 6 (2-14) months [17 events (30%)]. In the multivariate Cox regression analysis, worsening of RA PLS was significantly associated with clinical deterioration (hazard ratio: 4.87; 95% CI: 1.26-18.76; p = 0.022). Patients with worsened RA PLS had a significantly poorer prognosis than those with stable or improved RA PLS (log-rank p = 0.012). By contrast, PS and PACS did not yield significant prognostic information.Conclusion: Treatment-naive patients with PAH may show different RA functional response patterns to PAH therapy. These functional patterns are significantly associated with clinically relevant outcome measures. Improvements of RA function are driven by reductions of afterload, RV remodeling, and RV dysfunction

Data_Sheet_1_Hepatorenal dysfunction in patients with chronic thromboembolic pulmonary hypertension.docx

BackgroundCardiac interactions with organs such as the liver or kidneys have been described in different cardiovascular diseases. However, the clinical relevance of hepatorenal dysfunction in chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We determined the association of hepatorenal dysfunction (measured using the Model for End-stage Liver Disease Sodium [MELDNa] score) with right heart function and survival in patients with CTEPH.MethodsWe analyzed all patients with CTEPH in the Giessen Pulmonary Hypertension Registry who had available MELDNa scores and were not taking vitamin K antagonists. The MELDNa score was calculated as MELD score − serum Na − (0.025 * MELD score * (140 − serum Na)) + 140; the MELD score was calculated as 10*(0.957*ln(creatinine)+0.378*ln(bilirubin)+1.12*ln(International Normalized Ratio))+6.43.ResultsSeventy-two patients were included (74% female; median [Q1, Q3] MELDNa: 9 [6, 11]). MELDNa correlated well with right atrial and ventricular function and pulmonary hemodynamics. Forward regression analysis revealed that hepatorenal dysfunction mainly depends on right atrial strain and tricuspid regurgitation, but not right ventricular systolic dysfunction. Hepatorenal dysfunction predicted mortality at baseline and follow-up (adjusted hazard ratios [95% confidence intervals] per unit increase of MELDNa: 1.6 [1.1, 2.4] and 1.8 [1.1, 2.9], respectively). Changes in hepatorenal function also predicted mortality.ConclusionHepatorenal dysfunction in CTEPH is primarily associated with venous congestion rather than cardiac forward failure. As a surrogate parameter for hepatorenal dysfunction, MELDNa is a simple method to identify at-risk patients at baseline and follow-up.</p

Unmasking right ventricular-arterial uncoupling during fluid challenge in pulmonary hypertension

Background: Patients with pulmonary hypertension (PH) frequently show preserved right ventricular (RV) function at rest. However, volume challenge may uncover pending RV dysfunction. We aimed to assess the physiological and prognostic impact of RV-pulmonary arterial (RV-PA) uncoupling during volume challenge in patients with precapillary PH. Methods: We prospectively assessed 32 patients with PH (pulmonary arterial hypertension, n = 27; inoperable chronic thromboembolic disease, n = 5) and 4 controls using invasive pressure-volume (PV) catheterization. PV loops were recorded during preload reduction (balloon occlusion of inferior vena cava; baseline) and acute volume loading (200 ml saline in 20 s). Contractility (multi-beat end-systolic elastance [Ees]), arterial elastance (Ea), and RV-PA coupling (Ees/Ea) were obtained at baseline and at maximum volume loading (MVL). Results: Median [interquartile range] time to MVL was 19 [18-22] s. Ees/Ea significantly declined from baseline (0.89 [0.69-1.23]) to MVL (0.16 [0.12-0.34]; p < 0.001) in patients with PH but remained stable in controls (baseline: 1.08 [0.94-1.80]; MVL: 1.01 [0.80-2.49]; p = 0.715). The same pattern was observed for Ees, while Ea remained unchanged. The percent decline of RV-PA coupling (ΔEes/Ea) during fluid challenge was significantly associated with pulmonary resting hemodynamics, RV ejection fraction (RVEF), and RV end-diastolic volume. Kaplan-Meier analysis revealed that patients with PH who had a smaller ΔEes/Ea (<−65%) had a significantly better prognosis (log-rank p = 0.0389). In multivariate Cox regression analysis, clinical worsening was predicted by ΔEes/Ea (hazard ratio: 0.96 [95% confidence interval: 0.93-1.00]) and RVEF (hazard ratio: 0.95 [95% confidence interval: 0.92-0.98]). Conclusions: Assessment of PV loops during fluid challenge uncovers exhausted RV coupling reserve with severely reduced contractility in PH. RV-PA uncoupling during volume challenge can be predicted by pulmonary resting hemodynamics and RVEF. RV-PA uncoupling during fluid challenge and RVEF (as a noninvasive correlate) are predictors of clinical worsening. Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03403868 (January 19, 2018).SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe