Dutogliptin in Combination with Filgrastim in Early Recovery Post-Myocardial Infarction-The REC-DUT-002 Trial.

Patients with acute myocardial infarction are at high risk for developing heart failure due to scar development. Although regenerative approaches are evolving, consistent clinical benefits have not yet been reported. Treatment with dutogliptin, a second-generation DPP-4 inhibitor, in co-administration with filgrastim (G-CSF) has been shown to enhance endogenous repair mechanisms in experimental models. The REC-DUT-002 trial was a phase 2, multicenter, double-blind placebo-controlled trial which explored the safety, tolerability, and efficacy of dutogliptin and filgrastim in patients with ST-elevation Myocardial Infarction (STEMI). Patients (n = 47, 56.1 ± 10.7 years, 29% female) with STEMI, reduced left ventricular ejection fraction (EF ≤ 45%) and successful revascularization following primary PCI were randomized to receive either study treatment or matching placebo. Cardiac magnetic resonance imaging (cMRI) was performed within 72 h post-PCI and repeated after 3 months. The study was closed out early due to the SARS-CoV-2 pandemic. There was no statistically significant difference between the groups with respect to serious adverse events (SAE). Predefined mean changes within cMRI-derived functional and structural parameters from baseline to 90 days did not differ between placebo and treatment (left ventricular end-diastolic volume: +13.7 mL vs. +15.7 mL; LV-EF: +5.7% vs. +5.9%). Improvement in cardiac tissue health over time was noted in both groups: full-width at half-maximum late gadolinium enhancement (FWHM LGE) mass (placebo: -12.7 g, treatment: -19.9 g; p = 0.23). Concomitant treatment was well tolerated, and no safety issues were detected. Based on the results, the FDA and EMA have already approved an adequately powered large outcome trial.

Simplified Acute Physiology Score 3 Performance in Austrian COVID-19 Patients Admitted to Intensive Care Units with and without Diabetes.

This study evaluated and compared the performance of simplified acute physiology score 3 (SAPS 3) for predicting in-hospital mortality in COVID-19 patients admitted to intensive care units (ICUs) with and without diabetes in Austria. The Austrian national public health institute (GÖG) data of COVID-19 patients admitted to ICUs (n = 5850) were analyzed. Three versions of SAPS 3 were used: standard equation, Central European equation, and Austrian equation customized for COVID-19 patients. The observed in-hospital mortality was 38.9%, 42.9%, and 37.3% in all, diabetes, and non-diabetes patients, respectively. The overall C-statistics was 0.69 with an insignificant (p = 0.193) difference between diabetes (0.70) and non-diabetes (0.68) patients. The Brier score was > 0.20 for all SAPS 3 equations in all cohorts. Calibration was unsatisfactory for both standard and Central European equations in all cohorts, whereas it was satisfactory for the Austrian equation in diabetes patients only. The SAPS 3 score demonstrated low discrimination and accuracy in Austrian COVID-19 patients, with an insignificant difference between diabetes and non-diabetes. All equations were miscalibrated particularly in non-diabetes patients, while the Austrian equation showed satisfactory calibration in diabetes patients only. Both uncalibrated and calibrated versions of SAPS 3 should be used with caution in COVID-19 patients.

A biopsychosocial model of severe fear of COVID-19.

INTRODUCTION: COVID-19 is a respiratory infection that causes not only somatic health issues, but also frequently psychosocial burdens. The aims of this study were to investigate biopsychosocial factors that might further aggravate fear of COVID-19, and to establish a biopsychosocial model of severe fear of COVID-19. METHODS: 368 participants were included in this study. Biopsychosocial factors observed comprised biological factors (somatic risk), psychological factors (state/trait anxiety, physical symptoms of anxiety, severe health anxiety, specific phobias, depression), and psychosocial factors (social support, financial losses, social media consumption, social contacts with COVID-19 infected people). Psychometric questionnaires included State-Trait Anxiety Inventory, Beck's Anxiety Inventory, Whiteley-Index / Illness Attitude Scales, Specific Phobia Questionnaire, WHO-5 and Social Support Survey. RESULTS: 162/368 (44.0%) participants had almost no fear, 170/368 (46.2%) participants had moderate fear, and 45/368 (12.2%) participants had severe fear of COVID-19. Female participants showed higher levels of fear of COVID-19 than male participants (gender: χ2 = 18.47, p<0.001). However, the level of fear of COVID-19 increased in male participants when they had contact with people who were infected with COVID-19, while in contrast the level of fear of COVID-19 decreased in female participants when they had such contacts [ANCOVA: fear of COVID-19 (contact x gender): F(1,363) = 5.596, p = .019]. Moreover, participants without relationships showed higher levels of fear of COVID-19 (marital status: χ2 = 14.582, p = 0.024). Furthermore, financial losses due to the COVID-19 were associated with higher levels of fear of COVID-19 [ANCOVA: fear of COVID-19(financial loss x gender): F(1, 363) = 22.853, p< .001]. Multiple regression analysis revealed female gender, severe health anxiety (WI-IAS) and state /trait anxiety (STAI) as significant predictors of severe fear of COVID-19. CONCLUSION: In this study significant predictors of severe fear of COVID-19 were female gender, pre-existing state and trait anxiety, as well as severe health anxiety. The finding of significant predictors of fear of COVID-19 might contribute to detect people who might suffer most from severe, overwhelming fear of COVID-19 at an early stage.

COVID-19 In-Hospital Mortality in People with Diabetes Is Driven by Comorbidities and Age-Propensity Score-Matched Analysis of Austrian National Public Health Institute Data.

BACKGROUND: It is a matter of debate whether diabetes alone or its associated comorbidities are responsible for severe COVID-19 outcomes. This study assessed the impact of diabetes on intensive care unit (ICU) admission and in-hospital mortality in hospitalized COVID-19 patients. METHODS: A retrospective analysis was performed on a countrywide cohort of 40,632 COVID-19 patients hospitalized between March 2020 and March 2021. Data were provided by the Austrian data platform. The association of diabetes with outcomes was assessed using unmatched and propensity-score matched (PSM) logistic regression. RESULTS: 12.2% of patients had diabetes, 14.5% were admitted to the ICU, and 16.2% died in the hospital. Unmatched logistic regression analysis showed a significant association of diabetes (odds ratio [OR]: 1.24, 95% confidence interval [CI]: 1.15-1.34, p < 0.001) with in-hospital mortality, whereas PSM analysis showed no significant association of diabetes with in-hospital mortality (OR: 1.08, 95%CI: 0.97-1.19, p = 0.146). Diabetes was associated with higher odds of ICU admissions in both unmatched (OR: 1.36, 95%CI: 1.25-1.47, p < 0.001) and PSM analysis (OR: 1.15, 95%CI: 1.04-1.28, p = 0.009). CONCLUSIONS: People with diabetes were more likely to be admitted to ICU compared to those without diabetes. However, advanced age and comorbidities rather than diabetes itself were associated with increased in-hospital mortality in COVID-19 patients.

Complications and mortality of cardiovascular emergency admissions during COVID-19 associated restrictive measures.

While hospital admissions for myocardial infarction (MI) and pulmonary embolism (PE) are decreased during the COVID-19 pandemic, controversy remains about respective complication and mortality rates. This study evaluated admission rates, complications, and intrahospital mortality for selected life-threatening cardiovascular emergencies (MI, PE, and acute aortic dissection (AAD)) during COVID-19-associated restrictive social measures (RM) in Styria, Austria. By screening a patient information system for International Statistical Classification of Diseases and Related Health Problems (ICD) diagnosis codes covering more than 85% of acute hospital admissions in the state of Styria (~1.24 million inhabitants), we retrospectively identified patients with admission diagnoses for MI (I21, I22), PE (I26), and AAD (I71). Rates of complications such as cardiogenic shock and cardiopulmonary resuscitation, treatment escalations (thrombolysis for PE), and mortality were analyzed by patient chart review during 6 weeks following onset of COVID-19 associated RM, and during respective time frames in the years 2016 to 2019. 1,668 patients were included. Cumulative admissions for MI, PE and AAD decreased (RR 0.77; p<0.001) during RM compared to previous years. In contrast, intrahospital mortality increased by 65% (RR 1.65; p = 0.041), mainly driven by mortality following MI (RR 1.80; p = 0.042). PE patients received more frequently thrombolysis treatment (RR 3.63; p = 0.006), while rates of cardiogenic shock and cardiopulmonary resuscitation remained unchanged. Of 226 patients hospitalized during RM, 81 patients with suspected COVID-19 disease were screened for SARS-CoV-2 infection with only 5 testing positive. Thus, cumulative hospital admissions for cardiovascular emergencies decreased during COVID-19 associated RM while intrahospital mortality increased.