Objective To evaluate fenebrutinib, an oral and highly selective noncovalent inhibitor of Bruton's tyrosine kinase (BTK), in patients with active rheumatoid arthritis (RA). Methods Patients with RA and an inadequate response to methotrexate (MTX) (cohort 1; n = 480) were randomized to receive fenebrutinib (50 mg once daily, 150 mg once daily, or 200 mg twice daily), adalimumab (40 mg every other week), or placebo. Patients with RA and an inadequate response to tumor necrosis factor inhibitors (cohort 2; n = 98) received fenebrutinib (200 mg twice daily) or placebo. Both cohorts continued MTX therapy. Results In cohort 1, the percentages of patients in whom American College of Rheumatology 50% improvement criteria (ACR50) was achieved at week 12 were similar in the fenebrutinib 50 mg once daily and placebo groups, and were higher in the fenebrutinib 150 mg once daily group (28%) and 200 mg twice daily group (35%) than in the placebo group (15%) (P = 0.016 and P = 0.0003, respectively). Fenebrutinib 200 mg twice daily and adalimumab (36%) were comparable (P = 0.81). In cohort 2, ACR50 was achieved in more patients receiving fenebrutinib 200 mg twice daily (25%) than placebo (12%) (P = 0.072). The most common adverse events in the fenebrutinib groups included nausea, headache, anemia, and upper respiratory tract infections. Fenebrutinib had significant effects on myeloid and B cell biomarkers (CCL4 and rheumatoid factor). Fenebrutinib and adalimumab caused overlapping as well as distinct changes in B cell and myeloid biomarkers. Conclusion Fenebrutinib demonstrates efficacy comparable to adalimumab in patients with an inadequate response to MTX, and safety consistent with existing immunomodulatory therapies for RA. These data support targeting both B and myeloid cells via this novel mechanism for potential efficacy in the treatment of RA.

There is a growing body of evidence for the protective role of vitamin D in diabetes mellitus (DM), infection, cancer, cardiovascular disease, immune disorders and kidney function. Considering the reported high prevalence of vitamin D insufficiency among kidney transplant recipients (KTRs), the aim of this study was to assess the influence of immunosuppressive therapy and other factors on vitamin D status in such patients. The study included 289 KTRs (189 males and 100 females) who consented to participate. The first test for 25-hydrohyvitamin D [25(OH)D] was performed by a validated liquid chromatography–tandem mass spectrometry method. Influence of immunosuppressive drugs and previously reported predictors on vitamin D status was assessed by descriptive statistics, univariate and multivariate regression. Our results showed that only 53 patients (18.34%) of the studied KTRs were vitamin D sufficient. In addition to a well expected positive association between serum 25(OH)D and summer blood sampling (p < 0.05) and inverse relationship between vitamin D status and DM, gender (female) and body mass index, serum 25(OH)D was found to be inversely associated with calcineurin inhibitors (CNI) (p < 0.05) and unaffected by other immunosuppressive agents. Our study demonstrated high prevalence of vitamin D insufficiency after kidney transplantation in the studied cohort of patients. Apart from female gender, winter months, DM and overweight, the use of CNI could be considered an additional significant predictor of lower 25(OH)D in Bulgarian KTRs.

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Due to the harmful effects of nanoparticles in the environment, their effective removal from aqueous media is of great importance. This paper described the research on the silver nanoparticles (Ag-NPs) sorption on biochars obtained from different feedstock types. The sorbents were produced through pyrolysis (double-barrel method) of the vineyard (BV), paulownia tree (BP), and tobacco (BT). BV exhibited the highest specific surface area, porosity, value of variable surface charge, and content of surface acidic functional groups among the used biochars. The pseudo-second order model best described the obtained adsorption kinetics, whereas the Freundlich model accounted for the registered adsorption data. The Ag-NPs removal was highly efficient in the case of BV, especially in the nanoparticle concentration range 50–500 mg/L. Thus, this biochar can be considered as an ecofriendly, effective, low-cost organic adsorbent, potentially used in the aqueous media purification.

Introduction.Recurrent urinary tract infections (rUTIs) after kidney transplantation (KT) are associated with significant decrease in graft survival. There is a growing body of evidence for the pleiotropic effects of vitamin D (VD), including immunomodulatory and antibacterial effect. The number of studies on VD’s pleiotropic effects in kidney transplant recipients (KTRs) however is low. The aim of our study was to assess the influence of VD on the incidence of recurrent UTIs after KT.Methods. The KTRs were tested for 25-hydroxyvitamin D (25VD) between 1.05.2012 and 30.11.2012. Patients within 12 months of transplantation, performed parathyroidectomy, concomitant intake of calcineurin inhibittors and mTOR inhibitors, advanced liver disease and VD supplementation were excluded from the study. Recurrent UTIs were defined as more than 3 episodes of active UTI within the last 12 months of testing for 25VD. Statistical analysis was carried out with SPSS version 22.0 and included descriptive statistics, Mann-Whitney U test. Determination of total 25VD was performed by a validated LC-MS/MS method.Results.A total of 275 patients met the above-mentioned criteria (males 182, females 93). The mean 25VD in patients with rUTIs (n=14) was 51.41±25.17 nmol/L, whereas in the group without rUTIs (n=261) the level was 60.35±23.29 nmol/L. After matching the two groups for seasonal factors (sampling for 25VD in July, August, September) and gender 169 patients were selected, and 11 were with rUTIs. No significant difference was detected in the 25VD level in the two groups (53.30±18.37 vs 49.08±21.04 nmol/L), p=0.342.Conclusions.Despite the higher 25VD in the KTRs without rUTIs, the difference between the two groups remained insignificant.