Incidence and predictors of thrombotic complications in 4742 patients with COVID-19 or other acute infectious respiratory diseases: A propensity score-matched study

Background. A prothrombotic state, attributable to excessive inflammation, cytokine storm, hypoxia, and immobilization, is a feature of SARS-CoV-2 infection. Up to 30% of patients with severe COVID-19 remain at high risk of thromboembolic events despite anticoagulant administration, with adverse impact on in-hospital prognosis. Methods. We retrospectively studied 4742 patients with acute infectious respiratory disease (AIRD); 2579 were diagnosed to have COVID-19 and treated with heparin, whereas 2163 had other causes of AIRD. We compared the incidence and predictors of total, arterial, and venous thrombosis, both in the whole population and in a propensity score-matched subpopulation of 3036 patients (1518 in each group). Results. 271 thrombotic events occurred in the whole population: 121 (4.7%) in the COVID-19 group and 150 (6.9%) in the no-COVID-19 group (p < 0.001). No differences in the incidence of total (p = 0.11), arterial (p = 0.26), and venous (p = 0.38) thrombosis were found between the two groups after adjustment for confounding clinical variables and in the propensity score-matched subpopulation. Likewise, there were no significant differences in bleeding rates between the two groups. Clinical predictors of arterial thrombosis included age (p = 0.006), diabetes mellitus (p = 0.034), peripheral artery disease (p < 0.001), and previous stroke (p < 0.001), whereas history of solid cancer (p < 0.001) and previous deep vein thrombosis (p = 0.007) were associated with higher incidence of venous thrombosis. Conclusions. Hospitalized patients with COVID-19 treated with heparin do not seem to show significant differences in the cumulative incidence of thromboembolic events as well as in the incidence of arterial and venous thrombosis separately, compared with AIRD patients with different etiological diagnosis

Restricted T-Cell Repertoire in the Epicardial Adipose Tissue of Non-ST Segment Elevation Myocardial Infarction Patients

Aims: Human epicardial adipose tissue, a dynamic source of multiple bioactive factors, holds a close functional and anatomic relationship with the epicardial coronary arteries and communicates with the coronary artery wall through paracrine and vasocrine secretions. We explored the hypothesis that T-cell recruitment into epicardial adipose tissue (EAT) in patients with non-ST segment elevation myocardial infarction (NSTEMI) could be part of a specific antigen-driven response implicated in acute coronary syndrome onset and progression. Methods and Results: We enrolled 32 NSTEMI patients and 34 chronic coronary syndrome (CCS) patients undergoing coronary artery bypass grafting (CABG) and 12 mitral valve disease (MVD) patients undergoing surgery. We performed EAT proteome profiling on pooled specimens from three NSTEMI and three CCS patients. We performed T-cell receptor (TCR) spectratyping and CDR3 sequencing in EAT and peripheral blood mononuclear cells of 29 NSTEMI, 31 CCS, and 12 MVD patients. We then used computational modeling studies to predict interactions of the TCR beta chain variable region (TRBV) and explore sequence alignments. The EAT proteome profiling displayed a higher content of pro-inflammatory molecules (CD31, CHI3L1, CRP, EMPRINN, ENG, IL-17, IL-33, MMP-9, MPO, NGAL, RBP-4, RETN, VDB) in NSTEMI as compared to CCS (P < 0.0001). CDR3-beta spectratyping showed a TRBV21 enrichment in EAT of NSTEMI (12/29 patients; 41%) as compared with CCS (1/31 patients; 3%) and MVD (none) (ANOVA for trend P < 0.001). Of note, 11/12 (92%) NSTEMI patients with TRBV21 perturbation were at their first manifestation of ACS. Four patients with the first event shared a distinctive TRBV21-CDR3 sequence of 178 bp length and 2/4 were carriers of the human leukocyte antigen (HLA)-A*03:01 allele. A 3D analysis predicted the most likely epitope able to bind HLA-A3*01 and interact with the TRBV21-CDR3 sequence of 178 bp length, while the alignment results were consistent with microbial DNA sequences. Conclusions: Our study revealed a unique immune signature of the epicardial adipose tissue, which led to a 3D modeling of the TCRBV/peptide/HLA-A3 complex, in acute coronary syndrome patients at their first event, paving the way for epitope-driven therapeutic strategies

Mixed reality navigation of a systemic venous baffle obstruction: Unravelling the percutaneous approach in atrial switch operation

Congenital heart diseases in adulthood (ACHD) are an increasing evidence, hence the need of interventional procedures due to late-onset complications of early-life corrective surgery. Systemic venous baffle (SVB) obstruction occurs in up to 10% of transposition of great arteries after atrial switch operation (TGA-ASO, Supplementary material online, Movie S1) and stenting is the first-line recommended treatment. However, SVB arrangement with the pulmonary systemic baffle remains challenging to interpret, representing a possible limitation for transcatheter approach. Herein, we exploited a novel image-based platform to set up the percutaneous relief of a superior vena cava (SVC) pathway obstruction in TGA-ASO. Three-dimensional (3D) pre-catheterization anatomy (Panel A) was investigated employing a holographic augmented reality prototype (Panel A1, ARTINESS, Milan, Italy) to directly inspect the 3D anatomy (Panel A2) and perceive the severity of SVB stenosis and its longitudinal extension (Panel A3; Supplementary material online, Movie S2). Multi-planar analysis of SVC cross-sections (Panel B1) effectively supported the stent sizing. A 48-mm ANDRA stent (Andramed, Reutlingen, Germany) was deployed on the stenotic baffle and post-dilated with a balloon-in-balloon catheter 18 50 mm (BiBVR Catheter, NUMED, Hopkinton, NY, USA; Supplementary material online, Movie S3); peak-to-peak SVC gradient reverted from 6 mmHg to a baseline value. Post-catheterization 3D computer tomography scan reconstruction was navigated through mixed reality, pinpointing the results of the procedure (Panel B2, Supplementary material online, Movie S4). By enhancing the structural ACHD comprehension, 3D analysis and holographic navigation are promising tools for diagnostic and therapeutic applications, with a glance on their educational potential

Thyroid dysfunction in lung cancer patients treated with immune checkpoint inhibitors (ICI): Role of race, gender, and concurrent chemotherapy in a multiethnic urban cohort.

e21622 Background: Immune-related adverse events (irAE) associated with ICI have been reported, but remain poorly understood. We sought to characterize patterns of thyroid dysfunction—one of the most common irAE—in a large cohort of ethnically-diverse lung cancer patients treated with ICI. Methods: A retrospective chart review of lung cancer patients receiving an anti-PD1 or PD-L1 agent from January 2016 to July 2019 was performed. Subjects included had normal baseline thyroid function. Thyrotoxicosis and hypothyroidism was defined as thyroid-stimulating hormone level less than 0.4 and greater than 4.6, respectively. Time to event analysis with inverted Kaplan Meier curves and log-rank tests were used to compare thyroid dysfunction among race, gender, and treatment subgroups. Results: We identified 256 subjects: 206 had normal baseline thyroid function and 76 went on to develop thyroid dysfunction. Rates of thyroid dysfunction by one year occurred at similar frequencies among all races. Thyrotoxicosis occurred at significantly higher rates in Black (25, 31.7%) than in White (8, 12.9%) and Hispanic (7, 16.7%) subjects. In contrast, hypothyroidism occurred more often in White (13, 21.0%) and Hispanic (18, 42.9%) than in Black (12, 15.2%) subjects. Gender and concurrent chemotherapy showed no significant association with thyroid dysfunction. Of subjects with thyrotoxicosis (N = 42), hypothyroidism followed in 33.3% (N = 14) with 1 subject receiving methimazole and 13 levothyroxine. In those subjects, median time to thyrotoxicosis and hypothyroidism was 4.0 and 7.2 weeks, respectively. Conclusions: Despite the higher prevalence of non-ICI-related thyroid disease among females and the anticipated immunosuppressive effect of chemotherapy, neither gender nor chemotherapy correlated with thyroid dysfunction; however, race did. Black subjects exhibited significantly higher rates of thyrotoxicosis. Our findings are consistent with prior research showing that thyrotoxicosis, including Graves’ disease, occurs more often in Blacks. While the pathogenesis of ICI-related thyroid dysfunction is unclear, the early onset of thyrotoxicosis demonstrated by our study calls for careful monitoring, especially for particular races. [Table: see text] </jats:p