High frequency of thrombocytopenia in patients with acute-on-chronic liver failure treated with linezolid.

BACKGROUND: Linezolid is an effective antibiotic reagent for Gram-positive bacterial infection; its most common side effect is thrombocytopenia. However, the incidence of thrombocytopenia in patients with acute-on-chronic liver failure (ACLF) who underwent linezolid therapy was unclear. The present study was to evaluate the incidence of thrombocytopenia in ACLF and non-ACLF patients treated with linezolid and the risk factors of thrombocytopenia in these patients. METHODS: Thirty-five patients with ACLF who had been subjected to intravenous administration of 600 mg linezolid every 12 hours for more than 7 days were categorized as a ACLF treatment (ACLF-T) group, 72 patients without ACLF treated with the same dosage of linezolid were recruited as a non-ACLF treatment (NACLF-T) group, and 70 patients with ACLF without linezolid treatment served as an ACLF control (ACLF-C) group. The incidences of thrombocytopenia in different groups were compared at day 14. Risk factors were investigated using logistic regression analysis. RESULTS: The incidence of thrombocytopenia at day 14 was significantly higher in the ACLF-T group than in the ACLF-C group (20/35 vs 24/70, P=0.025) and in the NACLF-T group (20/35 vs 9/72, P<0.001). Multivariate analysis showed that the ratio of platelet count (day 7/day 0)<1 (OR=10.021; P=0.012) and the baseline platelet count (OR=0.985; P=0.036) were independent risk factors of thrombocytopenia at day 14 of linezolid therapy. CONCLUSIONS: The benefits of linezolid treatment should outweigh the risk of thrombocytopenia in patients with ACLF. Moreover, it is necessary to closely monitor the platelet count during linezolid therapy especially in the patients with decreased platelet count at day 7 of linezolid therapy.

Chemo- and Regioselective Alkylation of Pyridine N-Oxides with Titanacyclopropanes.

While titanacyclopropanes are used to react mainly with ester, amide, and cyano to undergo cyclopropanation, herein they react preferentially with pyridine N-oxide to accomplish C2-H alkylation beyond these functionalities with double regioselectivity. After being pyridylated at the less hindered C-Ti bond, the remaining C-Ti bond of titanacyclopropanes can be further functionalized by various electrophiles, allowing facile introduction of complex alkyls onto the C2 of pyridines. Its synthetic potential has been demonstrated by late-stage diversification of drugs.

Role of bile acids in liver diseases mediated by the gut microbiome.

The intensive crosstalk between the liver and the intestine performs many essential functions. This crosstalk is important for natural immune surveillance, adaptive immune response regulation and nutrient metabolism and elimination of toxic bacterial metabolites. The interaction between the gut microbiome and bile acids is bidirectional. The gut microbiome regulates the synthesis of bile acids and their biological signaling activity and circulation via enzymes. Similarly, bile acids also shape the composition of the gut microbiome by modulating the host's natural antibacterial defense and the intestinal immune system. The interaction between bile acids and the gut microbiome has been implicated in the pathophysiology of many intestinal and extra intestinal diseases, especially liver diseases. As essential mediators of the gut-liver crosstalk, bile acids regulate specific host metabolic pathways and modulate the inflammatory responses through farnesoid X-activated receptor and G protein-coupled bile acid receptor 1. Several clinical trials have demonstrated the signaling effects of bile acids in the context of liver diseases. We hypothesize the existence of a gut microbiome-bile acids-liver triangle and explore the potential therapeutic strategies for liver diseases targeting the triangle.

Risk factors, clinical features, and short-term prognosis of spontaneous fungal peritonitis in cirrhosis: A matched case-control study.

BACKGROUND: Spontaneous peritonitis is one of the most common infectious complications in cirrhotic patients with ascites. Spontaneous fungal peritonitis (SFP) is a type of spontaneous peritonitis that is a less recognized but devastating complication in end-stage cirrhosis. Although high mortality was previously noted, scant data are available to fully define the factors responsible for the occurrence of SFP and its mortality. AIM: To illustrate the differences between SFP and spontaneous bacterial peritonitis (SBP) and discuss the risk factors for the occurrence of SFP and its short-term mortality. METHODS: We performed a matched case-control study between January 1, 2007 and December 30, 2018. Patients with SFP were included in a case group. Sex-, age-, and time-matched patients with SBP were included in a control group and were further divided into control-1 group (positive bacterial culture) and control-2 group (negative bacterial culture). The clinical features and laboratory parameters, severity models, and prognosis were compared between the case and control groups. Logistic regression analysis was used to determine the risk factors for occurrence, and the Cox regression model was used to identify the predictive factors for short-term mortality of SFP. RESULTS: Patients with SFP exhibited more severe systemic inflammation, higher ascites albumin and polymorphonuclear neutrophils, and a worsened 15-d mortality than patients in the control groups. Antibiotic administration (case vs control-1: OR = 1.063, 95%CI: 1.012-1.115, P = 0.014; case vs control-2: OR = 1.054, 95%CI: 1.014-1.095, P = 0.008) remarkably increased the occurrence of SFP or fungiascites. Hepatorenal syndrome (HR = 5.328, 95%CI: 1.050-18.900) and total bilirubin (µmol/L; HR = 1.005, 95%CI: 1.002-1.008) represented independent predictors of SFP-related early mortality. CONCLUSION: Long-term antibiotic administration increases the incidence of SFP, and hepatorenal syndrome and total bilirubin are closely related to short-term mortality.