Background: Acute pulmonary embolism (PE) has a wide spectrum of outcomes, but the best method to risk-stratify normotensive patients for adverse outcomes remains unclear.Methods: A multicentre retrospective cohort study of acute PE patients admitted from emergency departments in Calgary, Canada, between 2012 and 2017 was used to develop a refined acute PE risk score. The composite primary outcome of in-hospital PE-related death or haemodynamic decompensation. The model was internally validated using bootstrapping and the prognostic value of the derived risk score was compared to the Bova score.Results: Of 2067 patients with normotensive acute PE, the primary outcome (haemodynamic decompensation or PE-related death) occurred in 32 (1.5%) patients. In simplified Pulmonary Embolism Severity Index high-risk patients (n=1498, 78%), a multivariable model used to predict the primary outcome retained computed tomography (CT) right–left ventricular diameter ratio ≥1.5, systolic blood pressure 90–100 mmHg, central pulmonary artery clot and heart rate ≥100 beats·min⁻¹with a C-statistic of 0.89 (95% CI 0.82–0.93). Three risk groups were derived using a weighted score (score, prevalence, primary outcome event rate): group 1 (0–3, 73.8%, 0.34%), group 2 (4–6, 17.6%, 5.8%), group 3 (7–9, 8.7%, 12.8%) with a C-statistic 0.85 (95% CI 0.78–0.91). In comparison the prevalence (primary outcome) by Bova risk stages (n=1179) were stage I 49.8% (0.2%); stage II 31.9% (2.7%); and stage III 18.4% (7.8%) with a C-statistic 0.80 (95% CI 0.74–0.86).Conclusions: A simple four-variable risk score using clinical data immediately available after CT diagnosis of acute PE predicts in-hospital adverse outcomes. External validation of the Calgary Acute Pulmonary Embolism score is required.

While the use of topical drops for the delivery of drugs to the anterior of the eye is well accepted, it is far from efficient with as little as 5% of the drug instilled on the eye actually reaching the target tissue. The ability to prolong the residence time on the eye is desirable. Based on the acceptability of 2-hydroxyethyl methacrylate based polymers in contact lens applications, the current work focuses on the development of a poly(2-hydroxyethyl methacrylate (HEMA)) nanoparticle system. The particles were modified to allow for degradation and to permit mucoadhesion. Size and morphological analysis of the final polymer products showed that nano-sized, spherical particles were produced. FTIR spectra demonstrated that the nanoparticles comprised poly(HEMA) and that 3-(acrylamido)phenylboronic acid (3AAPBA), as a mucoadhesive, was successfully incorporated. Degradation of nanoparticles containing N,N′-bis(acryloyl)cystamine (BAC) after incubation with DL-dithiothreitol (DTT) was confirmed by a decrease in turbidity and through transmission electron microscopy (TEM). Nanoparticle mucoadhesion was shown through an in-vitro zeta potential analysis.

Cardiogenic shock is associated with poor clinical outcomes. There is a paucity of prospective data examining the efficacy and safety of inotropic therapy in patients with cardiogenic shock and renal dysfunction. This study sought to examine the treatment effect of milrinone compared to dobutamine in relation to renal function. In this post hoc analysis of the DOREMI (Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock) trial, we examined clinical outcomes with milrinone compared to dobutamine after stratification based on baseline estimated glomerular filtration rate (eGFR) 60 ml/min/1.73 m² and acute kidney injury (AKI). The primary outcome was the composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Baseline eGFR <60 ml/min/1.73 m² and AKI were observed in 78 (45%) and 124 (65%) of patients, respectively. The primary outcome and death from any cause occurred in 99 (52%) and 76 (40%) patients, respectively. eGFR <60 ml/min/1.73 m² did not appear to modulate the treatment effect of milrinone compared to dobutamine. In contrast, there was a significant interaction between the treatment effect of milrinone compared to dobutamine and AKI with respect to the primary outcome (P interaction = 0.02) and death (P interaction = 0.04). The interaction was characterized by lower risk of primary outcome and death with milrinone compared to dobutamine in patients without, but not with, AKI. In patients requiring inotropic support for cardiogenic shock, baseline renal dysfunction and AKI are common. A modulating effect of AKI on the relative efficacy of milrinone compared to dobutamine was observed, characterized by attenuation of a potential clinical benefit with milrinone compared to dobutamine in patients who develop AKI.

During acute pulmonary embolism (PE) a compensatory increase in right ventricular (RV) contractility is required to match increased afterload to maintain right ventricular-pulmonary arterial (RV-PA) coupling. The aim of this study was to assess the prognostic utility of RV-PA decoupling in acute PE. We assessed the association between measures of transthoracic echocardiography (TTE)-derived RV-PA coupling including tricuspid annular plane systolic excursion (TAPSE)/right ventricular systolic pressure (RVSP) and right ventricular fractional area change (FAC)/RVSP as well as stroke volume index (SVI)/RVSP (a measure of pulmonary artery capacitance) with adverse PE-related events (in-hospital PE-related mortality or cardiopulmonary decompensation) using logistic regression analysis. In 820 normotensive patients TTE-derived markers of RV-PA coupling were associated with PE-related adverse events. For each 0.1 mm/mmHg decrease in TAPSE/RVSP the odds of an adverse event increased by 2.5-fold [adjusted OR (aOR) 2.49, 95% confidence interval (CI) 1.46–4.24, p = 0.001], for every 0.1%/mmHg decrease in FAC/RVSP the odds of an adverse event increased by 1.4-fold (aOR 1.42, CI 1.09–1.86, p = 0.010), and for every 0.1 mL/mmHg m² decrease in SVI/RVSP the odds of an event increased by 2.75-fold (aOR 2.78, CI 1.72–4.50, p < 0.001). In multivariable analysis, TAPSE/RVSP and SVI/RVSP were independent of other risk stratification methods including computed tomography-derived right ventricular dysfunction (RVD), the Bova score, and subjective assessment of TTE-derived RVD. In patients with normotensive acute PE, TTE-derived measures of RV-PA coupling are associated with adverse in-hospital PE-related events and provide incremental value in the risk assessment beyond computed tomography-derived RVD, the Bova score, or subjective TTE-derived RVD.