An increase in CD62Ldim neutrophils precedes the development of pulmonary embolisms in COVID-19 patients.

OBJECTIVES: A high incidence of pulmonary embolism (PE) is reported in patients with critical coronavirus disease 2019 (COVID-19). Neutrophils may contribute to this through a process referred to as immunothrombosis. The aim of this study was to investigate the occurrence of neutrophil subpopulations in blood preceding the development of COVID-19 associated PE. METHODS: We studied COVID-19 patients admitted to the ICU of our tertiary hospital between 19-03-2020 and 17-05-2020. Point-of-care fully automated flow cytometry was performed prior to ICU admission, measuring the neutrophil activation/maturation markers CD10, CD11b, CD16 and CD62L. Neutrophil receptor expression was compared between patients who did or did not develop PE (as diagnosed on CT angiography) during or after their ICU stay. RESULTS: Among 25 eligible ICU patients, 22 subjects were included for analysis, of whom nine developed PE. The median (IQR) time between neutrophil phenotyping and PE occurrence was 9 (7-12) days. A significant increase in the immune-suppressive neutrophil phenotype CD16bright /CD62Ldim was observed on the day of ICU admission (P = 0.014) in patients developing PE compared to patients who did not. CONCLUSION: The increase in this neutrophil phenotype indicates that the increased number of CD16bright /CD62Ldim neutrophils might be used as prognostic marker to predict those patients that will develop PE in critical COVID-19 patients.

Systematic Review of the Co-Prevalence of Arterial Aneurysms Within the Vasculature.

OBJECTIVE: Aneurysms are considered focal manifestations of a systemic vascular condition, and various studies report co-prevalence of aneurysms in different vascular beds. Insight into profiles of patients at risk of multiple aneurysms is lacking, and few clinical algorithms exist if additional screening is indicated. This systematic review assessed the co-prevalence of aneurysms in different vascular beds and analysed putative risk factors for multiple aneurysms. METHODS: Medline, Embase, and Cochrane libraries were searched up to February 2020 for studies reporting co-prevalence of aneurysms in different vascular beds using the keywords: "aneurysm", "co-prevalence", or synonyms. All studies were reviewed by two authors independently. Studies were excluded if they described concomitant treatment of multi-aneurysms, or if the aneurysm was reported solely bilateral, post-dissection, mycotic, traumatic, iatrogenic, or caused by a connective tissue disease. Radar plots were used to indicate studies that found an association between the investigated features and aneurysm co-prevalence against those that did not. RESULTS: Thirty-two studies met the inclusion criteria, describing in total 16 353 patients of whom 2 015 had at least one additional aneurysm. The weighted co-prevalence was 16.9% (95% confidence interval [CI] 11.8-22.6), I2 > 90%. At least 19 combinations of aneurysms were described, mostly derived from retrospective studies. Seventeen of 32 (53%) studies described concurrent aneurysms in patients with an abdominal aortic aneurysm. Predominantly positive associations were found for higher age, hypertension, stenotic disease, presence of multiple (at least three) aneurysms, and primary aneurysm size. CONCLUSION: Approximately one in six patients with a primary aneurysm harbours an additional aneurysm, increasing to one in four if the patient has a popliteal artery aneurysm. Higher age, hypertension, stenotic disease, presence of multiple (at least three) aneurysms, and primary aneurysm size were predictive of aneurysm co-prevalence. These clinical predictors may assist when deciding whether a patient with a primary aneurysm needs to be screened for additional aneurysms.

Stereotactic radiotherapy or metastasectomy for oligometastatic esophagogastric cancer: A nationwide population-based cohort study.

Background and purpose: This nationwide population-based study analyzed the outcomes of local treatment (i.e. stereotactic body radiotherapy [SBRT] or metastasectomy) or systemic therapy for oligometastatic disease (OMD) in patients with esophagogastric cancer in The Netherlands. Materials and methods: Between 2015 and 2016, all patients in The Netherlands with esophagogastric cancer and synchronous or metachronous OMD were eligible for inclusion. Patients who underwent local treatment of OMD (SBRT or metastasectomy) and/or systemic therapy were included. OMD was defined as distant metastases in 1 organ or 1 extra-regional lymph node region. The primary outcomes were overall survival (OS) and independent prognostic factors for OS. OS was calculated from diagnosis of OMD. Prognostic factors for OS were analyzed using a multivariable Cox proportional hazard model. Results: A total of 594 patients were included, of whom 83 underwent local treatment for OMD alone, 22 local treatment plus systemic therapy, and 489 systemic therapy alone. Median OS after local treatment for OMD alone was 16.0 months, local treatment plus systemic therapy 22.7 months, and after systemic therapy alone 8.5 months. Improved OS was independently associated with local treatment for OMD alone or combined with systemic therapy as compared with systemic therapy alone (hazard ratio [HR] 0.52, 95% CI: 0.31-0.90 and HR 0.42, 95% CI: 0.22-0.82, respectively) and a controlled primary tumor(HR 0.48, 95% CI: 0.27-0.86). Worse OS was independently associated with worse performance scores (HR 1.41, 95%: 1.32-1.75), poorly or undiffertumor as compared with good or moderadifferentiated tumor (HR 1.37, 95% CI: 1.06-1.76), and peritoneal as compared with lymph mode metastases (HR 1.39, 95% CI: 1.00-1.93). Conclusion: Local treatment of OMD alone or combined with systemic therapy was independently associated with improved OS as compared with systemic therapy alone in this population-based cohort study in The Netherlands. Randomized controlled trials are warranted to confirm these results.

Flow cytometric evaluation of the neutrophil compartment in COVID-19 at hospital presentation: A normal response to an abnormal situation.

Coronavirus disease 2019 (COVID-19) is a rapidly emerging pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Critical COVID-19 is thought to be associated with a hyper-inflammatory process that can develop into acute respiratory distress syndrome, a critical disease normally mediated by dysfunctional neutrophils. This study tested the hypothesis whether the neutrophil compartment displays characteristics of hyperinflammation in COVID-19 patients. Therefore, a prospective study was performed on all patients with suspected COVID-19 presenting at the emergency room of a large academic hospital. Blood drawn within 2 d after hospital presentation was analyzed by point-of-care automated flow cytometry and compared with blood samples collected at later time points. COVID-19 patients did not exhibit neutrophilia or eosinopenia. Unexpectedly neutrophil activation markers (CD11b, CD16, CD10, and CD62L) did not differ between COVID-19-positive patients and COVID-19-negative patients diagnosed with other bacterial/viral infections, or between COVID-19 severity groups. In all patients, a decrease was found in the neutrophil maturation markers indicating an inflammation-induced left shift of the neutrophil compartment. In COVID-19 this was associated with disease severity.

Thrombotic Events in COVID-19 Are Associated With a Lower Use of Prophylactic Anticoagulation Before Hospitalization and Followed by Decreases in Platelet Reactivity.

Background: Coronavirus disease of 2019 (COVID-19) is associated with a prothrombotic state and a high incidence of thrombotic event(s) (TE). Objectives: To study platelet reactivity in hospitalized COVID-19 patients and determine a possible association with the clinical outcomes thrombosis and all-cause mortality. Methods: Seventy nine hospitalized COVID-19 patients were enrolled in this retrospective cohort study and provided blood samples in which platelet reactivity in response to stimulation with ADP and TRAP-6 was determined using flow cytometry. Clinical outcomes included thrombotic events, and all-cause mortality. Results: The incidence of TE in this study was 28% and all-cause mortality 16%. Patients that developed a TE were younger than patients that did not develop a TE [median age of 55 vs. 70 years; adjusted odds ratio (AOR) = 0.96 per 1 year of age, 95% confidence interval (CI) 0.92-1.00; p = 0.041]. Furthermore, patients using preexisting thromboprophylaxis were less likely to develop a thrombotic complication than patients that were not (18 vs. 54%; AOR = 0.19, 95% CI 0.04-0.84; p = 0.029). Conversely, having asthma strongly increased the risk on TE development (AOR = 6.2, 95% CI 1.15-33.7; p = 0.034). No significant differences in baseline P-selectin expression or platelet reactivity were observed between the COVID-19 positive patients (n = 79) and COVID-19 negative hospitalized control patients (n = 21), nor between COVID-19 positive survivors or non-survivors. However, patients showed decreased platelet reactivity in response to TRAP-6 following TE development. Conclusion: We observed an association between the use of preexisting thromboprophylaxis and a decreased risk of TE during COVID-19. This suggests that these therapies are beneficial for coping with COVID-19 associated hypercoagulability. This highlights the importance of patient therapy adherence. We observed lowered platelet reactivity after the development of TE, which might be attributed to platelet desensitization during thromboinflammation.