Clinical Features of Patients Infected With Coronavirus Disease 2019 With Elevated Liver Biochemistries: A Multicenter, Retrospective Study.

BACKGROUND AND AIMS: In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) emerged in Wuhan, China. Although it has been reported that some patients with COVID-19 showed elevated liver biochemistries, there are few studies regarding the clinical features and prognosis of these patients. APPROACH AND RESULTS: In this multicenter, retrospective study, we collected data on laboratory-confirmed patients with COVID-19 from three hospitals in Wuhan, China, who died or were discharged between February 1, 2020, and February 20, 2020. Data on demographics, comorbidities, clinical symptoms, laboratory examinations on admission, complications, treatment, and outcome were collected. A total of 482 patients were enrolled in this study. Of those, 142 (29.5%) patients showed abnormal liver biochemistries on admission, and patients with elevated alanine aminotransferase, aspartate aminotransferase (AST), and total bilirubin (TBIL) accounted for 67.6%, 69.0%, and 16.2%, respectively. Those with abnormal liver biochemistries showed higher percentages of severe cases and comorbidities and were more likely to have dyspnea, chest distress or pain, and increased hemoglobin (Hb) on admission. Higher rates of complications and mortality and worse recovery when discharged were observed in patients with abnormal AST or TBIL. Multivariable regression analysis showed that chest distress or pain (odds ratio [OR], 1.765; P = 0.018), dyspnea (OR, 2.495; P = 0.001), elevated C-reactive protein level (OR, 1.007; P = 0.008), elevated white blood count (OR, 1.139; P = 0.013), and elevated Hb concentration (OR, 1.024; P = 0.001) were independent factors associated with elevated liver biochemistries in patients with COVID-19. CONCLUSIONS: Elevated liver biochemistries were common in patients with COVID-19. Patients with hypoxia or severe inflammation are more likely to experience increased liver biochemistries on admission. Those with abnormal AST or TBIL on admission are more likely to suffer from severe complications and death.

BAFF Blockade Attenuates Inflammatory Responses and Intestinal Barrier Dysfunction in a Murine Endotoxemia Model.

B cell-activating factor (BAFF) production is increased in septic patients. However, the specific role of BAFF in sepsis remains unknown. This study was designed to investigate the expression and function of BAFF in an experimental endotoxemia model and to identify the potential mechanisms. We established an endotoxemia mouse (6-8 weeks, 20-22 g) model by administering 30 mg/kg lipopolysaccharide (LPS). BAFF levels in the circulating system and organ tissues were measured 4 and 8 h after LPS injection. Survival rates in the endotoxemia mice were monitored for 72 h after BAFF blockade. The effects of BAFF blockade on systemic and local inflammation, organ injuries, and intestinal barrier function were also evaluated 4 h after LPS treatment. BAFF production was systemically and locally elevated after LPS challenge. BAFF blockade improved the survival rate, systemic inflammation, and multi-organ injuries. Moreover, BAFF blockade attenuated both intestinal inflammation and impaired intestinal permeability. BAFF blockade upregulated ZO-1 and occludin protein levels via the NF-κB/MLCK/MLC signaling pathway. These results suggested that BAFF blockade protects against lethal endotoxemia at least partially by alleviating inflammation, multi-organ injuries, and improving intestinal barrier function and provides a novel focus for further research on sepsis and experimental evidence for clinical therapy.

Interleukin-38 is elevated in inflammatory bowel diseases and suppresses intestinal inflammation.

There has been no report investigating the role of IL-38 in inflammatory bowel diseases (IBD). Therefore, we investigated the expression of IL-38 in IBD patients and its role in regulating intestinal inflammation. The levels of IL-38 were significantly elevated in the intestine of IBD patients and DSS-induced colitis mice. Immunofluorescence analysis revealed that B cell, not macrophage or T cell, was the source of IL-38 in the intestine. We found that rIL-38 treatment significantly attenuated DSS-induced colitis, including alleviation of weight loss, disease activity index, macroscopic changes and histological damage of colon, along with lower levels of IL-1ß and TNF-α. In vitro, rIL-38 significantly decreased the expression of proinflammatory cytokines in LPS-stimulated RAW 264.7 cells and BMDM. This is the first study suggesting that IL-38 may have a protective effect in IBD, which inhibits the production of proinflammatory cytokines from macrophages. IL-38 may represent a promising therapeutic strategy in IBD.

The culprit of mesalamine intolerance: case series and literature review.

BACKGROUND: Mesalamine is a first-line drug in the treatment of inflammatory bowel diseases, while its intolerance occasionally occurs in clinical practice. Most of adverse reactions are due to the active components, which may lead to step-up treatment, but excipients are sometimes regarded as the chief culprit and can be resolved by transferring to other preparations. Thus, distinguishing different kinds of intolerance is extremely important for clinical decision. CASE PRESENTATION: Here we reported two cases with mesalamine intolerance. One patient with 5-aminosalicylic acid intolerance had similar adverse reactions to the treatment of different preparations, while another patient with excipients intolerance failed to tolerate Salofalk but could take Pentasa with no symptoms. Meanwhile, clinical manifestations were analysed and the previous reports referring to excipients intolerance were summarized. It is interesting to found that the patients with excipients intolerance mainly presented with acute skin symptoms, such as skin rash, urticaria and angioedema. But the adverse effects of 5-ASA in previous reports include fever, headache, rash, nausea, vomiting, dyspepsia, hepatotoxicity, pancreatitis, interstitial nephritis, pneumonitis, pericarditis and so on. CONCLUSIONS: 5-aminosalicylic acid and excipients should be taken into consideration together when mesalamine-related adverse events occur. Of note, a diagnosis of excipient intolerance should be paid more attention in the patients with the presentation of acute skin symptoms.