An increased risk of venous thromboembolism (VTE) in patients with COVID-19 pneumonia admitted to intensive care unit (ICU) has been reported. Whether COVID-19 increases the risk of VTE in non-ICU wards remains unknown. We aimed to evaluate the burden of asymptomatic deep vein thrombosis (DVT) in COVID-19 patients with elevated D-dimer levels. Method: In this prospective study consecutive patients hospitalized in non-intensive care units with diagnosis of COVID-19 pneumonia and D-dimer > 1000 ng/ml were screened for asymptomatic DVT with complete compression doppler ultrasound (CCUS). The study was approved by the Institutional Ethics Committee. Results: The study comprised 156 patients (65.4% male). All but three patients received standard doses of thromboprophylaxis. Median days of hospitalization until CCUS was 9 (IQR 5-17). CCUS was positive for DVT in 23 patients (14.7%), of whom only one was proximal DVT. Seven patients (4.5%) had bilateral distal DVT. Patients with DVT had higher median D-dimer levels: 4527 (IQR 1925-9144) ng/ml vs 2050 (IQR 1428-3235) ng/ml; p < 0.001. D-dimer levels > 1570 ng/ml were associated with asymptomatic DVT (OR 9.1; CI 95% 1.1-70.1). D-dimer showed an acceptable discriminative capacity (area under the ROC curve 0.72, 95% CI 0.61-0.84). Conclusion:In patients admitted with COVID-19 pneumonia and elevated D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series. Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients. The aim of our study was to evaluate the burden of asymptomatic

BACKGROUND Increasing age is a risk factor for COVID-19 severity and mortality; emerging science implicates GM-CSF and dysregulated myeloid cell responses in the pathophysiology of severe COVID-19. METHODS We conducted a large, global, double-blind, randomized, placebo-controlled study evaluating a single 90 mg infusion of otilimab (human anti-GM-CSF monoclonal) plus standard of care in adults hospitalized with severe COVID-19 respiratory failure and systemic inflammation, stratified by age and clinical status. Primary outcome was the proportion of patients alive and free of respiratory failure at Day 28; secondary endpoints included all-cause mortality at Day 60. RESULTS Overall, 806 patients were randomized (1:1); 71% of patients receiving otilimab were alive and free of respiratory failure at Day 28 versus 67% receiving placebo, although this did not reach statistical significance (model-adjusted difference 5.3% [95% CI 0.8, 11.4]; p=0.09). However, there was a benefit in the pre-defined ≥70-year age group (model-adjusted difference 19.1% [95% CI 5.2, 33.1]; nominal p=0.009); these patients also had a reduction of 14.4% (95% CI 0.9, 27.9%; nominal p=0.04) in model-adjusted all-cause mortality at Day 60. Safety findings were comparable between otilimab and placebo, and consistent with severe COVID-19. CONCLUSIONS Although not statistically significant in the overall population, otilimab demonstrated a substantial benefit in patients aged ≥70, possibly reflecting a population that could benefit from therapeutic blocking of GM-CSF in severe COVID-19 where myeloid cell dysregulation is predominant. These findings are being confirmed in a further cohort of patients aged ≥70 in Part 2 of this study. (ClinicalTrials.gov number: NCT04376684).

BackgroundGranulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of coronavirus disease 2019 (COVID-19).MethodsIn this randomised, sequential, multicentre, placebo-controlled, double-blind study, adults aged 18–79 years (Part 1) or ≥70 years (Part 2) with severe COVID-19, respiratory failure, and systemic inflammation (elevated C-reactive protein/ferritin) received a single intravenous infusion of otilimab 90 mg (human anti–GM-CSF monoclonal antibody) plus standard care (NCT04376684). The primary outcome was the proportion of patients alive and free of respiratory failure at Day 28.ResultsIn Part 1 (N=806 randomised 1:1 otilimab:placebo), 71% of otilimab-treated patients were alive and free of respiratory failure at Day 28versus67% who received placebo; the model-adjusted difference of 5.3% was not statistically significant (95% CI −0.8, 11.4; p=0.09). A nominally significant model-adjusted difference of 19.1% (95% CI 5.2, 33.1; p=0.009) was observed in the predefined 70–79 years subgroup, but this was not confirmed in Part 2 (N=350 randomised) where the model-adjusted difference was 0.9% (95% CI −9.3, 11.2; p=0.86). Compared with placebo, otilimab resulted in lower serum concentrations of key inflammatory markers, including the putative pharmacodynamic biomarker CCL17, indicative of GM-CSF pathway blockade. Adverse events were comparable between groups and consistent with severe COVID-19.ConclusionsThere was no significant difference in the proportion of patients alive and free of respiratory failure at Day 28. However, despite the lack of clinical benefit, a reduction in inflammatory markers was observed with otilimab, in addition to an acceptable safety profile.

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(1) Background: The relationship between type 2 diabetes (T2DM) and pulmonary embolism (PE) has not been well stablished so far. We aim to analyze incidence, clinical conditions and in-hospital mortality (IHM) according to the presence of T2DM among patients hospitalized for suffering from PE. The factors associated with IHM were identified. (2) Methods: Patients aged ≥40 years hospitalized for PE from 2016 to 2018 included in the Spanish National Health System Hospital Discharge Database were analyzed. Dependent variables included incidence, IHM and length of hospital stay. Independent variables were age, sex, diagnosed comorbidities, thrombolytic therapy and inferior vena cava filter placement. Poisson and logistic regression models were constructed for multivariable analysis. (3) Results: Of the 47,190 hospitalizations for PE recorded, 16.52% had T2DM. Adjusted incidence of PE was higher among T2DM women (IRR 1.83; 95% CI: 1.58–1.96) and men (IRR 1.22; 95% CI: 1.18–1.27) than among non-diabetic subjects. Crude IHM in T2DM patients with PE was similar in both sexes but higher than in non-diabetic patients. Among T2DM patients with PE, risk factors for IHM included older age, comorbidity, atrial fibrillation and massive PE. Obesity was associated with lower IHM. Suffering T2DM was a risk of IHM (OR 1.15; 95% CI 1.05–1.26) after PE. (4) Conclusions: The incidence of PE is higher in T2DM men and women than in non-diabetic patients. T2DM was a risk factor for IHM after PE.

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We determined sex differences in the prevalence of obstructive sleep apnea (OSA) among patients hospitalized with pulmonary embolism (PE) in Spain (2016–2018). We also compared outcomes according to the presence of OSA, and identified variables associated with in-hospital-mortality (IHM) after PE using the Spanish National Hospital Discharge Database. We identified 46,794 hospital admissions for PE; of these, 5.47% had OSA. OSA was more prevalent among men than women (7.57% vs. 3.65%, p < 0.001), as in the general population. Propensity score matching did not reveal differences in concomitant conditions or procedures between patients with and without OSA, except for the use of non-invasive ventilation, which was more frequent in patients with OSA. IHM was similar in patients with and without OSA (3.58% vs. 4.31% for men and 4.39% vs. 4.93% for women; p > 0.05). Older age, cancer, atrial fibrillation, non-septic shock, and need for mechanical ventilation increased IHM in men and women with OSA hospitalized with PE. The logistic regression model showed no sex differences in IHM among patients with OSA.

Background: In Spain, colorectal cancer screening using the fecal occult blood test, targeted towards the 50–69 age bracket, was implemented on different dates. We aim to assess the temporal trend of colorectal cancer (CRC) screening uptake according to the year of screening implementation in each region and to identify predictors for the uptake of CRC screening. Methods: A cross-sectional study with 12,657 participants from the Spanish National Health Surveys 2011 and 2017 was used. Uptake rates were analyzed according to the date that the screening program was implemented. Results: For regions with programs implemented before 2011, the uptake rate increased 3.34-fold from 2011 to 2017 (9.8% vs. 32.7%; p < 0.001). For regions that implemented screening within the 2011–2016 period, the uptake rose from 4.3% to 13.2% (3.07-fold; p < 0.001), and for regions that implemented screening after 2016, the uptake increased from 3.4% to 8.8% (2.59-fold; p < 0.001). For the entire Spanish population, the uptake increased 3.21-fold (6.8% vs. 21.8%; p < 0.001). Positive predictors for uptake were older age, Spanish nationality, middle-to-high educational level, suffering chronic diseases, non-smoking and living in regions where screening programs were implemented earlier. Conclusions: The different periods for the implementation of CRC screening as well as sociodemographic and health inequalities may have limited the improvement in the screening uptake from 2011 to 2017 in Spain.