Validation of the SACOV-19 score for identifying patients at risk of complicated or more severe COVID-19: a prospective study.

PURPOSE: Identification of patients at risk of complicated or more severe COVID-19 is of pivotal importance, since these patients might require monitoring, antiviral treatment, and hospitalization. In this study, we prospectively evaluated the SACOV-19 score for its ability to predict complicated or more severe COVID-19. METHODS: In this prospective multicenter study, we included 124 adult patients with acute COVID-19 in three German hospitals, who were diagnosed in an early, uncomplicated stage of COVID-19 within 72 h of inclusion. We determined the SACOV-19 score at baseline and performed a follow-up at 30 days. RESULTS: The SACOV-19 score's AUC was 0.816. At a cutoff of > 3, it predicted deterioration to complicated or more severe COVID-19 with a sensitivity of 94% and a specificity of 55%. It performed significantly better in predicting complicated COVID-19 than the random tree-based SACOV-19 predictive model, the CURB-65, 4C mortality, or qCSI scores. CONCLUSION: The SACOV-19 score is a feasible tool to aid decision making in acute COVID-19.

Differential MHC-II expression and phagocytic functions of embryo-derived cardiac macrophages in the course of myocardial infarction in mice.

In mouse myocardial infarction, we combined lineage tracing of cardiac macrophages, mapping their ontogeny, with an analysis of their phenotype and phagocytic functions. While embryo-derived macrophages were most abundant in homeostasis, bone marrow-derived MHC-IIlo macrophages increased in both numbers and phagocytic capacity to clear necrotic cardiomyocytes early after ischemia/perfusion injury.

Impact of energy drink versus coffee consumption on periodic repolarization dynamics: an interventional study.

PURPOSE: Caffeinated beverages are consumed daily throughout the world. Caffeine consumption has been linked to dysfunction of the autonomic nervous system. However, the exact effects are still insufficiently understood. METHODS: Sixteen healthy individuals were included in the present non-randomized cross-over interventional study. All study subjects consumed a commercial energy drink (containing 240 mg caffeine), and in a second independent session coffee (containing 240 mg caffeine). High-resolution digital ECGs in Frank-lead configuration were recorded at baseline before consumption, and 45 min after consumption of the respective beverage. Using customized software, we assessed ECG-based biomarker periodic repolarization dynamics (PRD), which mirrors the effect of efferent cardiac sympathetic activity on the ventricular myocardium. RESULTS: The consumption of energy drinks resulted in an increase in PRD levels (3.64 vs. 5.85 deg2; p < 0.001). In contrast, coffee consumption did not alter PRD levels (3.47 vs 3.16 deg2, p = 0.63). The heart rates remained unchanged both after coffee and after energy drink consumption. Spearman analysis showed no significant correlation between PRD changes and heart rate changes (R = 0.34, p = 0.31 for coffee, R = 0.31, p = 0.24 for energy drink). CONCLUSION: Our data suggests that sympathetic activation after consumption of caffeinated beverages is independent from caffeine and might be mediated by other substances. TRIAL NUMBER: NCT04886869, 13 May 2021, retrospectively registered.

Comparison of balanced and unbalanced crystalloids as resuscitation fluid in patients treated for cardiogenic shock.

BACKGROUND: The efficacy and safety of saline versus balanced crystalloid solutions in ICU-patients remains complicated by exceptionally heterogenous study population in past comparative studies. This study sought to compare saline and balanced crystalloids for fluid resuscitation in patients with cardiogenic shock with or without out-of-hospital cardiac arrest (OHCA). METHODS: We retrospectively analyzed 1032 propensity score matched patients with cardiogenic shock from the Munich University Hospital from 2010 to 2022. In 2018, default resuscitation fluid was changed from 0.9% saline to balanced crystalloids. The primary endpoint was defined as 30-day mortality rate. RESULTS: Patients in the saline group (n = 516) had a similar 30-day mortality rate as patients treated with balanced crystalloids (n = 516) (43.1% vs. 43.0%, p = 0.833), but a higher incidence of new onset renal replacement therapy (30.2% vs 22.7%, p = 0.007) and significantly higher doses of catecholamines. However, OHCA-patients with a lactate level higher than 7.4 mmol/L had a significantly lower 30-day mortality rate when treated with saline (58.6% vs. 79.3%, p = 0.013). In addition, use of balanced crystalloids was independently associated with a higher mortality in the multivariate cox regression analysis after OHCA (hazard ratio 1.43, confidence interval: 1.05-1.96, p = 0.024). CONCLUSIONS: In patients with cardiogenic shock, use of balanced crystalloids was associated with a similar all-cause mortality at 30 days but a lower rate of new onset of renal replacement therapy. In the subgroup of patients after OHCA with severe shock, use of balanced crystalloids was associated with a higher mortality than saline. TRIAL REGISTRATION: LMUshock registry (WHO International Clinical Trials Registry Platform Number DRKS00015860).

Impact of Face Masks on Exercise Capacity and Lactate Thresholds in Healthy Young Adults.

BACKGROUND: Although many countries have introduced strict guidelines regarding mouth and nose coverage in public to contain infection rates during the SARS-CoV-2 pandemic, more information is needed regarding the impact of wearing face masks on lactate thresholds (LT) and performance parameters during exercise. METHODS: Ten healthy male and 10 healthy female subjects (age = 33.4 [10.26] y, body mass index = 23.52 [2.36] kg/m2) performed 3 incremental performance tests, wearing no mask (NM), surgical mask (SM), and filtering face piece mask class 2 (FFP2), with a cycle ergometer. The authors analyzed changes in the LT, in blood gas parameters, and in the rating of perceived exertion (RPE). RESULTS: Performance at LT remained unchanged in subjects wearing SM or FFP2 in comparison with NM (162.5 [50.6] vs 167.2 [58.9] vs 162.2 [58.4] W with NM, SM, and FFP2, respectively, P = .24). However, the peak performance was significantly reduced wearing FFP2 compared with NM (213.8 [71.3] vs 230.5 [77.27] W, FFP2 vs NM, respectively, P < .001). Capillary pCO2 was increased while wearing SM as well as FFP2 compared with NM (29 [3.1] vs 33.3 [4] vs 35.8 [4.9] mmHg with NM, SM, and FFP2, respectively; P < .001), and pO2 decreased under maximum performance (84 [6.7] vs 79.1 [7.5] vs 77.3 [8.2] mmHg with NM, SM, and FFP2, P < .01). Importantly, rating of perceived exertion was significantly increased by wearing FFP2 compared with NM at LT according to Mader (16.7 [2.7] vs 15.3 [1.8] FFP2 vs NM, respectively, P < .01). CONCLUSION: Wearing face masks during exercise showed no effect on LT, limited maximum performance, and induced discrete changes in capillary pCO2 and pO2 within the physiologic range while increasing RPE at LT.

ACE Inhibition Modulates Myeloid Hematopoiesis after Acute Myocardial Infarction and Reduces Cardiac and Vascular Inflammation in Ischemic Heart Failure.

AIMS: Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a cornerstone of drug therapy after myocardial infarction (MI) and improve left ventricular function and survival. We aimed to elucidate the impact of early treatment with the ACE inhibitor ramipril on the hematopoietic response after MI, as well as on the chronic systemic and vascular inflammation. Methods and Results: In a mouse model of MI, induced by permanent ligation of the left anterior descending artery, immediate initiation of treatment with ramipril (10 mg/k/d via drinking water) reduced cardiac inflammation and the number of circulating inflammatory monocytes, whereas left ventricular function was not altered significantly, respectively. This effect was accompanied by enhanced retention of hematopoietic stem cells, Lin-Sca1-c-Kit+CD34+CD16/32+ granulocyte-macrophage progenitors (GMP) and Lin-Sca1-c-Kit+CD150-CD48- multipotent progenitors (MPP) in the bone marrow, with an upregulation of the niche factors Angiopoetin 1 and Kitl at 7 d post MI. Long-term ACE inhibition for 28 d limited vascular inflammation, particularly the infiltration of Ly6Chigh monocytes/macrophages, and reduced superoxide formation, resulting in improved endothelial function in mice with ischemic heart failure. Conclusion: ACE inhibition modulates the myeloid inflammatory response after MI due to the retention of myeloid precursor cells in their bone marrow reservoir. This results in a reduction in cardiac and vascular inflammation with improvement in survival after MI.

Nox2+ myeloid cells drive vascular inflammation and endothelial dysfunction in heart failure after myocardial infarction via angiotensin II receptor type 1.

AIMS: Heart failure (HF) ensuing myocardial infarction (MI) is characterized by the initiation of a systemic inflammatory response. We aimed to elucidate the impact of myelomonocytic cells and their activation by angiotensin II on vascular endothelial function in a mouse model of HF after MI. METHODS AND RESULTS: HF was induced in male C57BL/6J mice by permanent ligation of the left anterior descending coronary artery. Compared to sham, HF mice had significantly impaired endothelial function accompanied by enhanced mobilization of Sca-1+c-Kit+ haematopoietic stem cells and Sca-1-c-Kit+ common myeloid and granulocyte-macrophage progenitors in the bone marrow as well as increased vascular infiltration of CD11b+Ly6G-Ly6Chigh monocytes and accumulation of CD11b+ F4/80+ macrophages, assessed by flow cytometry. Using mice with Cre-inducible expression of diphtheria toxin receptor in myeloid cells, we selectively depleted lysozyme M+ myelomonocytic cells for 10 days starting 28 days after MI. While the cardiac phenotype remained unaltered until 38 days post-MI, myeloid cell depletion attenuated vascular accumulation of Nox2+CD45+ cells, endothelial dysfunction, oxidative stress, and vascular expression of adhesion molecules and angiotensin II receptor type 1 (AT1R). Pharmacological blockade of this receptor for 4 weeks did not significantly alter cardiac function, but mimicked the effects of myeloid cell depletion: telmisartan (20 mg/kg/day, fed to C57BL/6J mice) diminished bone marrow myelopoesis and myeloid reactive oxygen species production, attenuated endothelial leucocyte rolling and vascular accumulation of CD11b+Ly6G-Ly6Chigh monocytes and macrophages, resulting in improved vascular function with less abundance of Nox2+CD45+ cells. CONCLUSION: Endothelial dysfunction in HF ensuing MI is mediated by inflammatory Nox2+ myeloid cells infiltrating the vessel wall that can be targeted by AT1R blockade.

Correlation of cardiac function and cerebral perfusion in a murine model of subarachnoid hemorrhage.

Cerebral hypoperfusion is a key factor for determining the outcome after subarachnoid hemorrhage (SAH). A subset of SAH patients develop neurogenic stress cardiomyopathy (NSC), but it is unclear to what extent cerebral hypoperfusion is influenced by cardiac dysfunction after SAH. The aims of this study were to examine the association between cardiac function and cerebral perfusion in a murine model of SAH and to identify electrocardiographic and echocardiographic signs indicative of NSC. We quantified cortical perfusion by laser SPECKLE contrast imaging, and myocardial function by serial high-frequency ultrasound imaging, for up to 7 days after experimental SAH induction in mice by endovascular filament perforation. Cortical perfusion decreased significantly whereas cardiac output and left ventricular ejection fraction increased significantly shortly post-SAH. Transient pathological ECG and echocardiographic abnormalities, indicating NSC (right bundle branch block, reduced left ventricular contractility), were observed up to 3 h post-SAH in a subset of model animals. Cerebral perfusion improved over time after SAH and correlated significantly with left ventricular end-diastolic volume at 3, 24, and 72 h. The murine SAH model is appropriate to experimentally investigate NSC. We conclude that in addition to cerebrovascular dysfunction, cardiac dysfunction may significantly influence cerebral perfusion, with LVEDV presenting a potential parameter for risk stratification.