Usefulness of bronchoalveolar lavage in suspect COVID-19 repeatedly negative swab test and interstitial lung disease

The diagnosis of coronavirus disease 2019 (COVID-19) relies on nasopharyngeal swab, which shows a 20–30% risk of false negativity [1]. Bronchoalveolar lavage (BAL) is reported to be useful in patients with pulmonary interstitial infiltrates on high-resolution computed tomography (HRCT). We investigated the usefulness of BAL in symptomatic patients with positive HRCT and a repeatedly negative swab test (‘grey zone’)

Colchicine in ischemic heart disease: the good, the bad and the ugly

Inflammation is the main pathophysiological process involved in atherosclerotic plaque formation, progression, instability, and healing during the evolution of coronary artery disease (CAD). The use of colchicine, a drug used for decades in non-ischemic cardiovascular (CV) diseases and/or systemic inflammatory conditions, stimulated new perspectives on its potential application in patients with CAD. Previous mechanistic and preclinical studies revealed anti-inflammatory and immunomodulatory effects of colchicine exerted through its principal mechanism of microtubule polymerization inhibition, however, other pleiotropic effects beneficial to the CV system were observed such as inhibition of platelet aggregation and suppression of endothelial proliferation. In randomized double-blinded clinical trials informing our clinical practice, low doses of colchicine were associated with the significant reduction of cardiovascular events in patients with stable CAD and chronic coronary syndrome (CCS) while in patients with a recent acute coronary syndrome (ACS), early initiation of colchicine treatment significantly reduced major adverse CV events (MACE). On the other hand, the safety profile of colchicine and its potential causal relationship to the observed increase in non-CV deaths warrants further investigation. For these reasons, postulates of precision medicine and patient-tailored approach with regards to benefits and harms of colchicine treatment should be employed at all times due to potential toxicity of colchicine as well as the currently unresolved signal of harm concerning non-CV mortality. The main goal of this review is to provide a balanced, critical, and comprehensive evaluation of currently available evidence with respect to colchicine use in the setting of CAD. Simil

Bile acids with differing hydrophilic-hydrophobic properties do not influence cytokine production by human monocytes and murine Kupffer cells

Bile acids have been proposed to exert immunological effects of potential pathogenic or therapeutic relevance, yet the experimental evidence remains preliminary. We reexamined the effects of a variety of bile salts with differing hydrophilic-hydrophobic properties on the production of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) from monocytes and Kupffer cells. Monocytes from healthy human donors and Kupffer cells from 5-week-old mice were incubated for up to 18 hours with or without varying concentrations of bile salts and lipopolysaccharide (LPS). Monocyte viability was greater than or equal to 95% with up to 250 mu mol/L sodium ursodeoxycholate and mu 90% with 200 mu mol/L chenodeoxycholate, decreasing sharply at higher concentrations. Kupffer cells were more vulnerable, particularly to chenodeoxycholate (viabilities of 25% and 0% at concentrations of 100 mu mol/L and 200 mu mol/L, respectively). In monocytes incubated in the presence of 20% fetal calf serum, neither ursodeoxycholate and chenodeoxycholate, nor a variety of other unconjugated and conjugated bile acids, tested up to their maximal noncytotoxic concentrations, influenced the IL-6 and TNF(alpha production, at any level of LPS stimulation. Similar to monocytes, incubation of murine Kupffer cells with ursodeoxycholate and chenodeoxycholate did not influence cytokine release. In contrast, the addition of 10 nmol/L dexamethasone to monocytes significantly decreased TNF-alpha and IL-6 release (69 +/- 11% and 48 +/- 15%, respectively). When monocytes were incubated with 200 mu mol/L chenodeoxycholate in the presence of lower concentrations of fetal calf serum (10% and 5%, respectively) a significant inhibition of cytokine release was observed, whereas incubation with ursodeoxycholate did not cause any effect. Flow cytometry using fluoresceinated LPS showed that chenodeoxycholate does not interact with the CD14 receptor, thus excluding the possibility of an interference with the LPS uptake by monocytes. Incubation with [C-14]-chenodeoxycholate showed that the intracellular bile acid uptake was inversely related to the concentration of fetal calf serum, being negligible (<3 fmol/cell) at the highest level. In conclusion, bile acids with widely different hydrophobicities are incapable of influencing the release of IL-6 and TNF alpha by monocytes and Kupffer cells, provided they are studied at noncytotoxic concentrations and in the presence of physiological amounts of proteins

Human immunodeficiency virus-induced cell death in cytokine-treated macrophages can be prevented by compounds that inhibit late stages of viral replication

The basis of the cytopathic effect induced by a laboratory strain and several clinical isolates of human immunodeficiency virus (HIV) in human macrophages cultured in the presence of macrophage colony-stimulating factor was studied. Infected macrophages die of necrosis, the consequence of the production of mature virions in infected cells. Cell death can be prevented by antiviral compounds that interfere with the assembly and budding of virions. Programmed cell death (apoptosis), a potential mechanism of HIV-mediated cell death in CD4 T lymphocytes, does not occur in infected macrophages as shown by electron microscopy, cytofluorometric and gel electrophoretic DNA analysis, and nuclear fluorescent staining by Hoechst and terminal dUTP-nick-end-labeling (TUNEL) assay. The data suggest that macrophage killing by HIV may occur in vivo. Thus, combination therapies that include compounds that inhibit the cytopathic effect of HIV in macrophages should be considered for AIDS patients