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Cigarette smoking causes lung inflammation, and a characteristic of inflammation is an increase in vascular permeability. To determine if cigarette smoke could alter endothelial permeability, we studied flux of radiolabeled albumin across monolayers of porcine pulmonary artery endothelium grown in culture on microporous membranes. Extracts (in either dimethylsulfoxide or phosphate-buffered saline) of cigarette smoke in a range estimate of concentrations simulating cigarette smoke exposure to the lungs in vivo caused a dose-dependent increase in albumin flux that was dependent on extracellular divalent cations and associated with polymerization of cellular actin. The effect was reversible, independent of the surface of endothelial cells exposed (either luminal or abluminal), and due primarily to components of the vapor phase of smoke. The effects occurred without evidence of cell damage, but subtle morphological changes were produced by exposure to the smoke extracts. These findings suggest that cigarette smoke can alter permeability of the lung endothelium through effects on cytoskeletal elements.

Background: There has been an increasing incidence of right-sided infective endocarditis (RSIE) due to the global rise of intravenous drug use (IVDU) and an increasing number of implantable cardiac electronic devices and central venous catheters. Our aim was to investigate differences in the clinical presentation, microbiological findings and prognosis of patients undergoing surgery for RSIE compared to left-sided infective endocarditis (LSIE). Methods: Relevant clinical data of all 432 consecutive patients undergoing valve surgery for infective endocarditis (IE) at our institution between January 2009 and December 2018 were retrospectively analyzed. Acquired data included patients' demographic and preoperative comorbidities, manifestation of IE according to the recently modified Duke Criteria, perioperative data and relevant clinical outcomes. Results: A total of 403 patients (93.3%) underwent surgery for LSIE and twenty-nine patients (6.7%) for RSIE. Eleven patients with RSIE (37.9%) showed a concomitant left-sided infection. Compared to LSIE, RSIE patients were significantly younger [47.5 (40.4-69.3) vs. 65.1 (53.7-74.6); P=0.008] and presented with less comorbidities such as hypertension (41.4% vs. 65.3%; P=0.010) and coronary artery disease (6.9% vs. 29.0%; P=0.010). Rates of IVDU (34.5% vs. 4.5%; P<0.001), human immunodeficiency virus (HIV) (10.3%vs. 1.7%; P=0.023) and hepatitis C virus (HCV) infection (24.1% vs. 5.2%; P=0.001) were greater in RSIE.The proportion of Staphylococcus aureus IE was significantly higher in RSIE compared to LSIE (37.9% vs. 21.1%; P=0.035). 30-day mortality was 6.9% after surgery for RSIE compared to 14.6% after operation for LSIE (P=0.372). Conclusions:Patients undergoing surgery for RSIE compared to LSIE presented with a higher rate of pulmonary septic emboli, more Staphylococcus aureus infections and larger vegetations. Larger multicenter prospective trials are needed to provide more reliable data on the clinical profile of these patients, in order to determine optimal surgical management.

Objectives Chronic kidney disease (CKD) is associated with an increased complication rate after cardiac interventions. Although CKD has a high prevalence among atrial fibrillation patients, the impact of CKD on periprocedural complications and the outcome after an interventional left atrial appendage closure (LAAC) is unclear. The present study, therefore, aimed to investigate whether CKD influences the procedure's effectiveness and safety. Methods LAARGE is a prospective, non-randomised registry. LAAC was conducted with different standard commercial devices, and the follow-up period was one year. CKD was defined by an eGFR < 60 mL/min/1.73 m 2 , and subgroups were further analysed (i.e. eGFR < 15, 15-29, and 30-59 mL/min/1.73 m 2 , respectively). Results Two hundred ninety-nine of 623 patients (48.0%) revealed a CKD. The prevalence of cardiovascular comorbidity, CHA 2 DS 2 -VASc score (4.9 vs. 4.2), and HAS-BLED score (4.3 vs. 3.5) was significantly higher in CKD patients (each p < 0.001). Implantation success was similarly high across all GFR groups (97.9%). Periprocedural MACCE (0.7 vs. 0.3%), and other major complications (4.7 vs. 3.7%) were comparably infrequent. Survival free of stroke was significantly lower among CKD patients within 1 year (82.0 vs. 93.0%; p < 0.001; consistent after adjustment for confounding factors), without significant accentuation in advanced CKD (i.e. eGFR < 30 mL/min/1.73 m 2 ; p > 0.05 vs. eGFR 30-59 mL/min/1.73 m 2 ). Non-fatal strokes were absolutely infrequent during follow-up (0 vs. 1.1%). Severe non-fatal bleedings were observed only among CKD patients (1.4 vs. 0%; p = 0.021). Conclusions Despite an increased cardiovascular risk profile of CKD patients, device implantation was safe, and LAAC was associated with effective stroke prevention across all CKD stages.

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