Search

Background: CT is thought to play a key role in coronavirus disease 2019 (COVID-19) diagnostic workup. The possibility of comparing data across different settings depends on the systematic and reproducible manner in which the scans are analyzed and reported. The COVID-19 Reporting and Data System (CO-RADS) and the corresponding CT severity score (CTSS) introduced by the Radiological Society of the Netherlands (NVvR) attempt to do so. However, this system has not been externally validated., Research Question: We aimed to prospectively validate the CO-RADS as a COVID-19 diagnostic tool at the ED and to evaluate whether the CTSS is associated with prognosis., Study Design and Methods: We conducted a prospective, observational study in two tertiary centers in The Netherlands, between March 19 and May 28, 2020. We consecutively included 741 adult patients at the ED with suspected COVID-19, who received a chest CT and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR (PCR). Diagnostic accuracy measures were calculated for CO-RADS, using PCR as reference. Logistic regression was performed for CTSS in relation to hospital admission, ICU admission, and 30-day mortality., Results: Seven hundred forty-one patients were included. We found an area under the curve (AUC) of 0.91 (CI, 0.89-0.94) for CO-RADS using PCR as reference. The optimal CO-RADS cutoff was 4, with a sensitivity of 89.4% (CI, 84.7-93.0) and specificity of 87.2% (CI, 83.9-89.9). We found a significant association between CTSS and hospital admission, ICU admission, and 30-day mortality; adjusted ORs per point increase in CTSS were 1.19 (CI, 1.09-1.28), 1.23 (1.15-1.32), 1.14 (1.07-1.22), respectively. Intraclass correlation coefficients for CO-RADS and CTSS were 0.94 (0.91-0.96) and 0.82 (0.70-0.90)., Interpretation: Our findings support the use of CO-RADS and CTSS in triage, diagnosis, and management decisions for patients presenting with possible COVID-19 at the ED., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) can lead to systemic coagulation activation and thrombotic complications., Objectives: To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID-19., Methods: Single-center cohort study of 198 hospitalized patients with COVID-19., Results: Seventy-five patients (38%) were admitted to the intensive care unit (ICU). At time of data collection, 16 (8%) were still hospitalized and 19% had died. During a median follow-up of 7 days (IQR, 3-13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis. The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10-22), 33% (95% CI, 23-43) and 42% (95% CI 30-54) respectively. For symptomatic VTE, these were 10% (95% CI, 5.8-16), 21% (95% CI, 14-30) and 25% (95% CI 16-36). VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02-5.5). The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17-37), 47% (95% CI, 34-58), and 59% (95% CI, 42-72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4-15), 9.2% (95% CI, 2.6-21), and 9.2% (2.6-21) at 7, 14, and 21 days)., Conclusions: The observed risk for VTE in COVID-19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE. Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival., (© 2020 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Background: The intestinal microbiome plays a versatile role in the etiology of arterial thrombosis. In venous thrombosis, driven chiefly by plasma coagulation, no such role has yet been established. We hypothesized that the intestinal microbiome composition affects coagulation in humans., Methods: We used healthy donor fecal microbiota transplant (FMT) to experimentally change the microbiome composition in metabolic syndrome patients. Thirty-five subjects were randomized in a blinded fashion to healthy donor FMT or autologous FMT as a control in a 2:1 ratio. We measured thrombin generation at baseline and after 6 weeks using automated calibrated thrombinography, and we determined plasma abundance of 32 coagulation related proteins using a targeted mass spectrometry-based quantitative proteomics assay with heavy labeled internal standards., Results: Healthy donor FMT prolonged the thrombinography lag time (median delta 0.0 versus 0.25 minutes, P = .039). The other thrombinography parameters showed no significant difference. Unsupervised cluster analysis suggested overall downregulation of coagulation related plasma proteins in subject clusters containing predominantly subjects that had a metabolic response to healthy donor FMT. FMT treatment status itself showed no clear clustering pattern with up- or downregulation, however, and proteins did not cluster according to an apparent biological grouping., Discussion: A single healthy donor FMT tends to modestly suppress the onset thrombin generation in metabolic syndrome patients, representing initial proof-of-principle that the intestinal microbiota composition might affect the coagulation system in humans. The findings merit external validation as a role for intestinal microbiota in coagulation can have clinically important implications., (© 2019 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.)

A 68-year-old woman, previously treated with embolization of the thoracic duct with Lipiodol (an ethiodized oil injection) and cyanoacrylate glue (a topical tissue adhesive), was admitted with an asymptomatic mass in the inferior vena cava (IVC) and right atrium. The mass was surgically removed, and pathologic analysis revealed a Lipiodol-containing thrombus. To our knowledge, this is the first clinicopathologic report of Lipiodol-induced thrombus presenting as an intracavitary mass., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

In this report, we present a patient who suffered from a myocardial infarction at an extremely young age. The only remarkable finding in the risk factor workup was a near undetectable high-density lipoprotein (HDL)-cholesterol plasma level (0.09 mmol/L). Genetic analysis of key genes involved in HDL metabolism resulted in the discovery of 2 very rare mutations in the ABCA1 and APOA1 genes. We discuss the effects of these mutations on HDL metabolism and reverse cholesterol transport and interpret these findings in relation to the extensive atherosclerosis at a very young age in this patient., (Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects of HDL. Patients with the orphan disease, familial hypoalphalipoproteinemia (FHA), are characterized by decreased tissue cholesterol removal and an increased atherogenic burden. We performed an open-label uncontrolled proof-of-concept study to evaluate the effect of infusions with a human apoA-I-containing HDL-mimetic particle (CER-001) on RCT and the arterial vessel wall in FHA. Subjects received 20 infusions of CER-001 (8 mg/kg) during 6 months. Efficacy was assessed by measuring (apo)lipoproteins, plasma-mediated cellular cholesterol efflux, fecal sterol excretion (FSE), and carotid artery wall dimension by MRI and artery wall inflammation by (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography scans. We included seven FHA patients: HDL-cholesterol (HDL-c), 13.8 [1.8-29.1] mg/dl; apoA-I, 28.7 [7.9-59.1] mg/dl. Following nine infusions in 1 month, apoA-I and HDL-c increased directly after infusion by 27.0 and 16.1 mg/dl (P = 0.018). CER-001 induced a 44% relative increase (P = 0.018) in in vitro cellular cholesterol efflux with a trend toward increased FSE (P = 0.068). After nine infusions of CER-001, carotid mean vessel wall area decreased compared with baseline from 25.0 to 22.8 mm(2) (P = 0.043) and target-to-background ratio from 2.04 to 1.81 (P = 0.046). In FHA-subjects, CER-001 stimulates cholesterol mobilization and reduces artery wall dimension and inflammation, supporting further evaluation of CER-001 in FHA patients., (Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.)

Background & Aims: Obesity has been associated with changes in the composition and function of the intestinal microbiota. Modulation of the microbiota by antibiotics also alters bile acid and glucose metabolism in mice. Hence, we hypothesized that short term administration of oral antibiotics in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism., Methods: In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500 mg t.i.d. or 7 days of vancomycin 500 mg t.i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured., Results: Vancomycin reduced fecal microbial diversity with a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly, vancomycin decreased fecal secondary bile acids with a simultaneous postprandial increase in primary bile acids in plasma (p<0.05). Moreover, changes in fecal bile acid concentrations were predominantly associated with altered Firmicutes. Finally, administration of vancomycin decreased peripheral insulin sensitivity (p<0.05). Amoxicillin did not affect any of these parameters., Conclusions: Oral administration of vancomycin significantly impacts host physiology by decreasing intestinal microbiota diversity, bile acid dehydroxylation and peripheral insulin sensitivity in subjects with metabolic syndrome. These data show that intestinal microbiota, particularly of the Firmicutes phylum contributes to bile acid and glucose metabolism in humans. This trial is registered at the Dutch Trial Register (NTR2566)., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objectives: Blocking the interleukin-6 pathway by tocilizumab (TCZ) has been associated with changes in the lipoprotein profile, which could adversely impact cardiovascular (CV) risk in patients with rheumatoid arthritis (RA). In the present study, we addressed the effect of TCZ on lipoproteins in both fasting and non-fasting state in RA patients and tested the effect of TCZ on LDL receptor (LDLr) expression in vitro., Methods: Twenty patients with active RA and an inadequate response to TNF blockers received monthly TCZ intravenously. On week 0, 1 and 6 blood was drawn before and after an oral fat load, the lipid profiles and HDL antioxidative capacity were measured. Effects of TCZ on LDLr expression in transfected HepG2 cells were subjected., Results: After 6 weeks of TCZ, total cholesterol increased by 22% (4.8 ± 0.9 to 5.9 ± 1.3 mmol/L; p < 0.001), LDLc by 22% (3.0 ± 0.6 to 3.6 ± 0.8 mmol/L; p < 0.001) and HDLc by 17% (1.4 ± 0.4 to 1.7 ± 0.7 mmol/L; p < 0.016). Fasting triglycerides (TG) increased by 48% (1.0 ± 0.4 to 1.4 ± 0.8 mmol/L; p = 0.011), whereas postprandial incremental area under the curve TG increased by 62% (p = 0.002). Lipid changes were unrelated to the change in disease activity or inflammatory markers. No difference in HDL antioxidative capacity was found. In vitro, LDLr expression in cultured liver cells was significantly decreased following TCZ incubation (P < 0.001)., Conclusions: TCZ adversely impacts on both LDLc as well as fasting and postprandial TG in patients with RA. The changes in hepatic LDLr expression following TCZ imply that adverse lipid changes may be a direct hepatic effect of TCZ. The net effect of TCZ on CV-morbidity has to be confirmed in future clinical trials., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)