Coronavirus disease 2019 (COVID-19) can lead to multiorgan damage. MicroRNAs (miRNAs) in blood reflect cell activation and tissue injury. We aimed to determine the association of circulating miRNAs with COVID-19 severity and 28 day intensive care unit (ICU) mortality. We performed RNA-Seq in plasma of healthy controls (n = 11), non-severe (n = 18), and severe (n = 18) COVID-19 patients and selected 14 miRNAs according to cell- and tissue origin for measurement by reverse transcription quantitative polymerase chain reaction (RT–qPCR) in a separate cohort of mild (n = 6), moderate (n = 39), and severe (n = 16) patients. Candidates were then measured by RT–qPCR in longitudinal samples of ICU COVID-19 patients (n = 240 samples from n = 65 patients). A total of 60 miRNAs, including platelet-, endothelial-, hepatocyte-, and cardiomyocyte-derived miRNAs, were differentially expressed depending on severity, with increased miR-133a and reduced miR-122 also being associated with 28 day mortality. We leveraged mass spectrometry-based proteomics data for corresponding protein trajectories. Myocyte-derived (myomiR) miR-133a was inversely associated with neutrophil counts and positively with proteins related to neutrophil degranulation, such as myeloperoxidase. In contrast, levels of hepatocyte-derived miR-122 correlated to liver parameters and to liver-derived positive (inverse association) and negative acute phase proteins (positive association). Finally, we compared miRNAs to established markers of COVID-19 severity and outcome, i.e. SARS-CoV-2 RNAemia, age, BMI, D-dimer, and troponin. Whilst RNAemia, age and troponin were better predictors of mortality, miR-133a and miR-122 showed superior classification performance for severity. In binary and triplet combinations, miRNAs improved classification performance of established markers for severity and mortality. Circulating miRNAs of different tissue origin, including several known cardiometabolic biomarkers, rise with COVID-19 severity. MyomiR miR-133a and liver-derived miR-122 also relate to 28 day mortality. MiR-133a reflects inflammation-induced myocyte damage, whilst miR-122 reflects the hepatic acute phase response.

Purpose: Dalbavancin is a novel lipoglycopeptide with potent activity against several gram-positive pathogens, an excellent safety profile and a long elimination half-life. Methods: In this case series observed at the University Hospital of Vienna between 2015 and 2017, all adult patients with gram-positive infections who received at least one dosage of dalbavancin were screened (n = 118). A total of 72 patients were included in the final analysis. The number of included patients stratified by the source of infection was: skin and soft tissue infection (SSTI) (n = 26), osteomyelitis (n = 20), spondylodiscitis (n = 14), acute septic arthritis (n = 4) and prosthetic joint infection (n = 8). Results: In 46 patients (64%), clinical cure was detected at the end of dalbavancin therapy without additional antibiotic therapy. Of the 26 patients who received additional antibiotic therapy other than dalbavancin, 15 patients (21%) showed no clinical improvement under dalbavancin therapy, four patients (5%) had side effects (nausea n = 1, exanthema n = 2, hyperglycemia n = 1), and in seven patients (10%) clinical improvement under dalbavancin therapy was detected but antibiotic therapy was de-escalated to an oral drug. Conclusion: We demonstrated high clinical effectiveness of dalbavancin for acute gram-positive infections primarily acute SSTI, acute septic arthritis, acute osteomyelitis and spondylodiscitis. In patients with biofilm-associated infection (chronic infection or joint prosthesis), source control was absolutely necessary for treatment success.

Essentials In acute coronary syndromes, dual antiplatelet therapy inhibits platelets but confers a bleeding risk. Healthy male volunteers received clopidogrel or ticagrelor plus aspirin or clopidogrel or ticagrelor alone. The decrease in β‐thromboglobulin in shed blood was comparable after single and dual antiplatelet therapy. We hypothesize that patients with acute coronary syndromes may not require dual antiplatelet therapy. Summary Background Dual antiplatelet therapy with a P2Y12 inhibitor and aspirin is standard in acute coronary syndromes. Dual antiplatelet therapy causes more bleeding than single antiplatelet therapy with a P2Y12 inhibitor. Objectives To compare the effects of dual and single antiplatelet therapies on hemostatic system activation. Patients/Methods In a randomized, parallel‐group, double‐blind, placebo‐controlled study, 44 healthy volunteers received clopidogrel (600 mg, then 150 mg d^–1) and aspirin (100 mg d^–1) or placebo for 7 days; An additional 44 volunteers received single‐dose ticagrelor (180 mg) and aspirin (300 mg) or placebo. β‐Thromboglobulin (β‐TG [IU L^–1]) and prothrombin fragment 1.2 (f1.2 [nmol L^–1]) were measured in blood obtained from bleeding time incisions. Data are given as geometric mean ratio (GMR [95% confidence interval]) to describe the differences in the first 2 h and as mean differences (Δ [95% confidence interval]) in area under the curve (AUC) to discriminate differences in effects over the total observation time. Results Clopidogrel plus aspirin and clopidogrel plus placebo reduced β‐TG by a GMR of 0.51 (0.42–0.63) and 0.54 (0.46–0.64) at 2 h. Ticagrelor plus aspirin and ticagrelor plus placebo decreased β‐TG by a GMR of 0.38 (0.26–0.57) and 0.47 (0.31–0.72). Ticagrelor plus aspirin and ticagrelor plus placebo reduced f1.2 by a GMR of 0.58 (0.45–0.75) and 0.55 (0.38–0.80); clopidogrel did not. Over 24 h, no difference in β‐TG occurred between clopidogrel plus aspirin and clopidogrel plus placebo (ΔAUC = −2.9 [−9.9 to 4.1]) or between ticagrelor plus aspirin and ticagrelor plus placebo (ΔAUC = −3.5 [−11.8 to 4.7]). No difference in f1.2 occurred between clopidogrel plus aspirin and clopidogrel plus placebo (ΔAUC = −4.2 [−10.2 to 1.8]) or between ticagrelor plus aspirin and ticagrelor plus placebo (ΔAUC = −3.6 [−10.9 to 3.7]). Conclusions P2Y12 inhibitor monotherapy and dual antiplatelet therapy inhibit hemostatic system activation to a comparable extent.

Venous thromboembolism (VTE) is a multicausal disease which recurs. Hematocrit is associated with a thrombotic risk. We aimed to investigate if hematocrit is associated with the recurrence risk. Patients with a first VTE were followed after anticoagulation. Patients with VTE provoked by a transient risk factor, natural inhibitor deficiency, lupus anticoagulant, homozygous or double heterozygous defects, cancer, or long-term antithrombotic treatment were excluded. The study endpoint was recurrent VTE. 150 (23%) of 653 patients had recurrence. Only high hematocrit was significantly associated with recurrence risk [hazard ratio (HR) for 1% hematocrit increase with the third tertile 1.08; 95% CI 1.01–1.15]. No or only a weak association for hematocrits within the first and second tertile was seen (HR 1.03; 95% CI 0.97–1.09, and 1.07; 95% CI 1.00–1.13). Hematocrit was associated with recurrence risk only among women. After five years, the probability of recurrence was 9.9% (95% CI 3.7%–15.7%), 15.6% (95% CI 9.7%–21.2%) and 25.5% (95% CI 15.1%–34.6%) in women, and was 29.2% (95% CI 21.1%–36.5%), 30.1% (95% CI 24.1%–35.7%) and 30.8% (95% CI 22.0%–38.7%) in men for hematocrits in the first, second and third tertile, respectively. Men had a higher recurrence risk (1.9; 95% CI 1.1–2.7; p = 0.03), which dropped by 23.5% after adjustment for hematocrit. Hematocrit was not a significant mediator of the sex-difference in recurrence risk (p = 0.223). High hematocrit is associated with the recurrence only in women. The different recurrence risk between men and women is possibly partly explained by hematocrit.

Venous thromboembolism (VTE) is a chronic disease, which tends to recur. Whether an abnormal fibrinolytic system is associated with an increased risk of VTE is unclear. We assessed the relationship between fibrinolytic capacity (reflected by clot lysis time [CLT]) and risk of recurrent VTE. We followed 704 patients (378 women; mean age 48 yrs) with a first unprovoked VTE for an average of 46 months after anticoagulation withdrawal. Patients with natural coagulation inhibitor deficiency, lupus anticoagulant, cancer, homozygosity for factor V Leiden or prothrombin mutation, or requirement for indefinite anticoagulation were excluded. Study endpoint was symptomatic recurrent VTE. For measurement of CLT, a tissue factor-induced clot was lysed by adding tissue-type plasminogen activator. Time between clot formation and lysis was determined by measuring the turbidity.135 (19%) patients had recurrent VTE. For each increase in CLT of 10 minutes, the crude relative risk (RR) of recurrence was 1.13 (95% CI 1.02–1.25; p = 0.02) and was 1.08 (95% CI 0.98–1.20; p = 0.13) after adjustment for age and sex. For women only, the adjusted RR was 1.14 (95% CI, 0.91–1.42, p = 0.22) for each increase in CLT of 10 minutes. CLT values in the 4^th quartile of the female patient population, as compared to values in the 1^st quartile, conferred a risk of recurrence of 3.28 (95% CI, 1.07–10.05; p = 0.04). No association between CLT and recurrence risk was found in men. Hypofibrinolysis as assessed by CLT confers a moderate increase in the risk of recurrent VTE. A weak association between CLT and risk of recurrence was found in women only.

Patients with spinal cord injury (SCI) are at risk of thrombosis and bleeding. Data on the risks during rehabilitation are inconsistent, and thromboprophylactic strategies are heterogeneous. We aimed to evaluate the thrombotic risk and bleeding events of SCI patients during rehabilitation. We retrospectively collected hospital record data of 263 consecutive SCI patients admitted at a rehabilitation clinic. 78 patients with acute venous thromboembolism (VTE) at the primary center, without acute trauma or lower extremity paresis, less than one month rehabilitation, or reasons for long-term therapeutic anticoagulation, were excluded. All patients received pharmacologic thromboprophylaxis throughout rehabilitation. Primary endpoint was objectively diagnosed VTE; secondary endpoint was bleeding. Of 185 patients, 162 (88%) were men; mean age was 47.8 years. 94 patients were tetraplegic, 91 paraplegic. During a mean (±SD) time of 5.1±2.1 months, VTE was diagnosed in 8 patients. After excluding five patients with VTE detected within 2 days after admission, the probability of developing VTE after 6 months of rehabilitation was 2% (95% CI 0–4.4%). Only high D-Dimer upon admission was associated with risk of VTE (adjusted HR 2.3, 95% CI 1.4–4.1). Of 24 bleedings, 14 (64%) occurred at the heparin injection site. Two patients had major bleeding and five had clinically relevant non major bleeding. SCI patients are at risk of VTE and bleeding during rehabilitation. Strategies need to be developed to identify these patients in order to initiate adequate anticoagulation. Direct oral anticoagulants, which have a favourable risk-benefit profile and are convenient, should be explored.