Highlights An exploratory randomized, controlled trial of baloxavir marboxil and favipiravir in COVID-19 patients were conducted. The free drug concentrations of baloxavir acid and favipiravir are generally lower than their respective EC50 values. Add-on either baloxavir or favipiravir to the current standard treatment resulted in no additional antiviral benefit.

BackgroundMucormycosis is a rare but devastating fungal infection primarily affecting immunocompromised patients such as those with hematological malignancy, bone marrow and solid organ transplantation, and patients with diabetes, and, even more rarely, immunocompetent patients. The objective of this study was to assess the prevalence and burden, both clinical and economic, of mucormycosis among hospitalized patients in the U.S.MethodsThis is a retrospective study using the Premier PerspectiveTM Comparative Database, with more than 560 participating hospitals covering 104 million patients (January 2005-June 2014). All hospitalizations in the database were evaluated for the presence of mucormycosis using either an ICD-9 code of 117.7 or a positive laboratory result for Mucorales. Hospitalizations were further required to have prescriptions of amphotericin B or posaconazole to be considered as mucormycosis-related hospitalizations. The prevalence of mucormycosis-related hospitalizations among all hospital discharges was estimated. Mortality rate at discharge, length of hospital stay, and readmission rates at 1 and 3 months were evaluated among mucormycosis-related hospitalizations. Cost per hospital stay and average per diem cost (inflated to 2014 USD) were reported.ResultsThe prevalence of mucormycosis-related hospitalizations was estimated as 0.12 per 10,000 discharges during January 2005-June 2014. It increased to 0.16 per 10,000 discharges if the definition of mucormycosis was relaxed to not require the use of amphotericin B or posaconazole. The median length of stay was 17 days, with 23% dead at discharge; readmission rates were high, with 30 and 37% of patients readmitted within one and three months of discharge, respectively. The average cost per hospital stay was $112,419, and the average per diem cost was $4,096.ConclusionsThe study provides a recent estimate of the prevalence and burden of mucormycosis among hospitalized patients. The high clinical and economic burden associated with mucormycosis highlights the importance of establishing active surveillance and optimizing prophylactic and active treatment in susceptible patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-2023-z) contains supplementary material, which is available to authorized users.

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Background: Oral microbiota is not only important for maintaining oral health but also plays a role in various oral diseases. However, studies regarding microbiome changes in oral lichen planus (OLP) are very limited. To the best of our knowledge, there has been only two studies investigating salivary microbiome changes in OLP. Therefore, the purpose of this study was to identify the characteristic microbial profile in the saliva of OLP patients, with or without erosive lesions, and compare that with recurrent aphthous ulcer (RAU), a common oral immunological disorder that also shows multiple erosive/ulcerative lesions. Whole saliva samples were collected from 20 patients with OLP (erosive E, n = 10 and non-erosive NE, n = 10), 10 patients with RAU (U) and 10 healthy controls (C). DNA was extracted from the saliva samples, and the 16S rDNA gene V4 hypervariable region was analyzed using Illumina sequencing. Results: We obtained 4949 operational taxonomic units (OTUs) from the V4 region in all saliva samples. Community composition analysis showed a clear decreased relative abundance of genera Streptococcus and Sphingomonas in saliva from RAU patients when compared to the other three groups. Relative abundance of Lautropia and Gemella were higher in E group, whereas relative abundance of Haemophilus and Neisseria were higher in NE group when compared to C group. Abiotrophia and Oribacterium were higher in OLP (combining E and NE groups), while Eikenella and Aggregatibacter were lower when compared to C group. There was statistically significance in α-diversity between E and RAU groups(p < 0.05). Significant differences in β-diversity were detected in bacteria between E and C; NE and C; as well as E and NE groups. The LDA effect size algorithm identified the g_Haemophilus might be the potential biomarker in NE group. Conclusions: We found that salivary microbiome in erosive OLP was significantly different from that found in RAU; and these changes may be related to the underlying disease process rather than presence of ulcerative/erosive lesions clinically. In addition, our findings in bacterial relative abundance in OLP were significantly different from the previously reported findings, which points to the need for further research in salivary microbiome of OLP.

Macrophage-orchestrated chronic inflammation plays an important role in cardiovascular disease, including accelerating the development of calcific aortic valve disease (CAVD). M1 and M2 macrophage polarization imbalances can alter intensity of inflammatory responses. Recombinant human interleukin 37 (IL-37) could be involved in regulating immune cell function to attenuate inflammation. This study aimed to identify IL-37 specifically modulates M1 polarization and investigate the underlying mechanism. Compared with normal valves, there are more M1 macrophages accumulation and less IL-37 expression in calcific aortic valves, which may indicate a negative relationship between IL-37 and M1 polarization. THP-1 cells could differentiate into resting macrophages with phorbol-12-myristate-13-acetate (PMA) and then polarize into M1 macrophages following treatment with lipopolysaccharide (LPS) and interferon gamma (IFN-γ). In vitro, recombinant human IL-37 attenuated the expression of inducible nitric oxide synthase (iNOS), CD11c, IL-6 and monocyte chemoattractant protein 1 (MCP-1) in M1 but augmented the expression of CD206 and IL-10 in M2. The suppression of M1 polarization was associated with the inhibition of the activation of the nuclear factor kappa B (NF-κB) and Notch1 signaling pathways. These results demonstrated that IL-37 inhibits the macrophages polarizing into M1 type via the inhibition of the Notch1 and nuclear factor kappa B pathways. In summary, IL-37 could be a potential therapeutic candidate for progressive CAVD by modulating M1 polarization and its orchestrated inflammation.

For patients with T2DM and CP, hyperglycemic status may exacerbate the inflammation state of gingival tissue by activating the NLRP3 pathway, and this abnormal host inflammatory response may contribute to further tissue breakdown.

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