An Open-Label, Randomized Trial Comparing Fidaxomicin With Oral Vancomycin for the Treatment of Clostridioides difficile Infection in Hospitalized Patients Receiving Concomitant Antibiotics for Concurrent Infections.

BACKGROUND: Recurrent Clostridioides difficile infection (rCDI) occurs frequently, and concomitant antibiotic (CA) during the initial episode for treatment of non-CDI is a major risk factor. We sought to address the comparative efficacy of fidaxomicin versus vancomycin in the setting of CA during the initial CDI episode. METHODS: We conducted a randomized, controlled, open-label trial at 2 hospitals in Ann Arbor, Michigan. We consecutively consented and enrolled hospitalized patients ≥18 years old with diarrhea, a positive test for C. difficile, and ≥1 qualifying CA. Complicated CDI, CDI treatment for >24 hours prior to enrollment, and planned long-term (>12 weeks) CA use were notable exclusions. Clinical cure was defined as resolution of diarrhea for 2 consecutive days maintained until 2 days after therapy, and rCDI as recurrent diarrhea with positive testing ≤30 days after initial treatment. Patients were randomized to fidaxomicin or vancomycin. RESULTS: Baseline characteristics were similar in the 2 groups of 144 patients. Rates of clinical cure (73% vs 62.9%, P = .195) and rCDI (3.3% vs 4.0%; P > .99) were similar for fidaxomicin and vancomycin in the intention-to-treat and per-protocol cohorts, respectively. Only 4 patients developed rCDI. CONCLUSIONS: In this study of patients with CDI receiving CA, a numerically higher proportion were cured with fidaxomicin versus vancomycin, but this result did not reach statistical significance. Overall recurrence was lower than anticipated in both arms compared with previous studies that did not extend duration of CDI treatment during CA. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT02692651).

Serum levels of IL-17 are elevated in patients with acute gouty arthritis.

Acute gouty arthritis (AGA) is one of the most common forms of auto-inflammatory arthritis. IL-17 is a key proinflammatory cytokine which has been implicated in several autoimmune diseases. However, to date little is known about the role of IL-17 in AGA. In the present study, we show that serum IL-17 levels are significantly elevated in AGA patients early in the onset of symptoms of gout, and decrease gradually as symptoms diminish. Correlation analysis indicated that IL-17 expression is not only positively correlated with disease activity, but is also correlated with serum levels of IL-1ß which plays a critical role in the differentiation of IL-17- γδT cells into IL-17+γδT cells. Flow cytometry analysis indicated that γδ T cells are a major source of IL-17 production during the early onset of AGA. We therefore identify IL-17 as a potential novel biomarker for AGA and suggest that targeting the γδ T cell/IL-17 immune axis is a potential strategy for treatment of acute flares of AGA.

Increased serum fibronectin levels in patients with hemorrhagic fever with renal syndrome.

BACKGROUND: In view of the role of fibronectin in adhesion, signal transduction pathways and the infectious disease process, changes in serum fibronectin levels may influence disease evolution and severity in patients with hemorrhagic fever with renal syndrome (HFRS). METHODS: The levels of fibronectin were measured in serum samples from 112 patients with HFRS at various phases, and 30 healthy individuals were monitored as controls. RESULTS: The serum levels of fibronectin in patients with HFRS at all clinical phases were higher than those in the controls, with the levels of patients at the fever, oliguric and polyuric phases of disease significantly different from controls (P < 0.01). The serum fibronectin concentration in the patients with more severe clinical disease types was higher than that in those with milder types. The serum fibronectin level in the more severe patient group was significantly higher than that in milder patient group at the oliguric phase (P < 0.05). CONCLUSIONS: Serum fibronectin concentration in patients with HFRS was increased and associated with disease phases and severity, suggesting the value of detection of fibronectin levels for evaluating HFRS disease progression and severity.

Intensity of platelet beta(3) integrin in patients with hemorrhagic fever with renal syndrome and its correlation with disease severity.

beta(3) Integrin has been identified as a cellular receptor for Hantaan virus, which causes hemorrhagic fever with renal syndrome (HFRS). To investigate the relationship between intensity of the platelet membrane beta(3) integrin (CD61) and disease severity, the percentage of CD61-positive platelets and the mean fluorescence intensities (MFI) of platelet CD61 were determined in patients with HFRS by flow cytometry. The intensity levels of CD61 in patients with HFRS were significantly higher than those in the controls and correlated with the clinical phases of the disease. The CD61 intensity at the oliguric phase was inversely correlated with platelet count and serum albumin, and positively correlated with white blood cell count, blood urea nitrogen, serum creatinine, and alanine aminotransferase levels. The results suggest that the intensity levels of platelet CD61 were elevated and associated with clinical phases and disease severity in patients with HFRS, and the intensity of platelet beta(3) integrin in patients with HFRS may be indicative of disease severity.

Serum thrombospondin-1 is altered in patients with hemorrhagic fever with renal syndrome.

Hemorrhagic fever with renal syndrome (HFRS) is a severe acute viral disease with pathological changes of impaired capillary and small vessels and thrombocytopenia. In this study, serum thrombospondin (TSP)-1 concentration in patients with HFRS was determined to explore its possible role in the pathogenesis of HFRS. The concentration of TSP-1 was measured using a competitive enzyme-linked immunoabsorbent assay. Significantly decreased levels of serum TSP-1 were observed in HFRS patients at febrile and hypotensive phases compared with those in the controls. The serum levels of TSP-1 in HFRS patients with more severe clinical types was reduced more profoundly than those in patients with milder clinical types at febrile and hypotensive phases, although the differences in TSP-1 were not significant. It was indicated that insufficient production or increased consumption of TSP-1, or both of these, may contribute to the impairment of capillary and small vessels and the development of hypotension at the early stage of HFRS, and the decreased degree may be associated with disease severity.

Frequency of CD19+CD24hiCD38hi regulatory B cells is decreased in peripheral blood and synovial fluid of patients with juvenile idiopathic arthritis: a preliminary study.

BACKGROUND: To understand the relationship between regulatory B cells (Bregs) and juvenile idiopathic arthritis (JIA), we analyzed the percentages of Bregs and their function in peripheral blood (PB) and synovial fluid (SF) of JIA patients. METHODS: Twenty-one JIA patients and 11 children with growing pain but without known rheumatic diseases as controls were included. The B cell phenotype and intracellular production of IL-10 of Bregs were assessed by flow cytometry. Mononuclear cells from PB and SF were stimulated to produce IL-10 in vitro for the identification of IL-10- producing regulatory B cells. RESULTS: The percentage of CD24hiCD38hi Bregs in the PB of JIA patients was significantly decreased compared to that in controls, and it was even lower in the SF of JIA patients compared to that in the PB. CD24hiCD38hi Bregs frequency was significantly lower in the PB of RF-positive patients than in RF-negative patients. Frequency of IL-10-producing regulatory B cells (B10 cells) was significantly lower in active JIA patients than that in inactive patients. CONCLUSIONS: The inability of the host to produce enough regulatory B cells in PB and especially in SF of JIA patients may contribute to the disease, especially the local inflammation.

Population genetics for Y-chromosomal STRs haplotypes of Chinese Tibetan ethnic minority group in Tibet.

Y-chromosomal STRs loci were analyzed from a sample of 119 healthy unrelated autochthonous male individuals of Chinese Tibetan ethnic minority group using a multiplex PCR system. Allele and haplotype frequencies for DYS19, DYS389 I, DYS389 II, DYS390, DYS391, DYS392, DYS393, DYS385a,b, DYS438, and DYS439 were determined by the Y-PLEXtrade mark 12 kit. The gene diversity values for the Y-STRs loci ranged from 0.3347 (DYS438) to 0.9547 (DYS385a,b). A total of 110 haplotypes were identified in the Y-STR loci, among which 104 were unique, while six occurred more than once. The overall haplotype diversity for the Y-STRs loci was 0.9981, and the discrimination capacity was 0.9897. The results in the present study can be used for routine forensic application in the region, and enrich Chinese ethnical genetic informational resources.

Genetic polymorphisms for 11 Y-STRs haplotypes of Chinese Yi ethnic minority group.

Eleven Y-STRs loci including minimal haplotypes (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, and DYS385a,b) and two additional loci, namely DYS438 and DYS439 have been co-amplified in 100 healthy unrelated males of Chinese Yi minority ethnic group using the Y-PLEX 5 and Y-PLEX 6 kit, in order to investigate allele and haplotype frequencies of Yi population, evaluate their usefulness in forensic paternity testing and human identification, and enrich Chinese population genetic informational resources. Out of a total of 100 individuals 85 showed different haplotypes, while 8 haplotypes occurred more than once. The overall haplotype diversity for 11 Y-STRs loci was 0.9945.

Genetic polymorphism for the PowerPlex 16 system from the Chinese Tujia Ethnic Minority Group.

POPULATIONS: The population studied was the Tujia population, living in the Hunan Province, China. Their ancestors had lived in the region for at least three generations. As a Chinese minority group, the Tujia ethnic group, with a population of 8,028,133 (year of 2000), is mainly distributed in the Wuling mountain area in the three provinces of Hunan, Hubei, and Sichuan. The Tujia population have their own language, which belongs to the Tibetan-Myanmese Language Group of the Chinese-Tibetan Language Family, but the large majority have come to speak the Han and Miao languages, now that the Tujias have been largely assimilated.

Low levels of serum vitronectin associated with clinical phases in patients with hemorrhagic fever with renal syndrome.

beta(3) integrin has been identified as a cellular receptor for Hantaan virus which causes hemorrhagic fever with renal syndrome (HFRS). As one of the ligands of beta(3) integrin, vitronectin (VN) may be altered in HFRS. In this study, changes of serum VN levels were determined in 112 patients with HFRS and 30 age- and sex-matched healthy controls by quantitative sandwich enzyme immunoassay. The levels of serum VN were analyzed in patients at various phases of HFRS and with different severity of clinical types. Serum VN levels in patients with HFRS, at all clinical phases except the convalescent phase, were significantly decreased compared with those in the controls (P < 0.01). The serum levels of VN decreased at febrile phase, maintained at the lowest status during hypotensive and oliguric phases, started to increase from polyuric phase and reached almost normal condition till convalescent phase. The levels of serum VN between patients with milder and more severe clinical types showed no significant difference at each phase (P > 0.05). These results suggest that VN level was altered during the course of HFRS and chronological changes of serum levels of VN may correlate with the evolution of the disease.