Background: Persistent infection following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) is a frustrating entity for the patient and rhinologist alike. Mupirocin nasal washes have been proposed as an efficacious treatment in such patients. Two small studies have reported excellent short‐term posttreatment outcomes; however, the long‐term microbiological outcomes following treatment are not known; likewise, the rate of mupirocin‐resistance following treatment has not been explored. Methods: This was a retrospective chart review of 61 patients with Staphylococcus aureus (S. aureus)‐positive surgically‐recalcitrant CRS having undergone 0.05% mupirocin nasal rinse treatment, twice daily for 4 weeks. Specific outcomes reported included posttreatment culture results, time to first posttreatment S. aureus culture, and mupirocin‐sensitivity following treatment. Results: Of 57 patients meeting minimal posttreatment follow‐up criteria, 42 (73.7%) progressed to microbiological failure by subsequently cultured S. aureus. Mean time to first positive culture was 144 days. Of the 42 patients who progressed to microbiological relapse, full antibiotic sensitivity data was available for 41; of these, only 1 was found to subsequently harbor a mupirocin‐resistant strain of S. aureus, thus yielding a posttreatment resistance rate of 2.4%. Conclusion: Treatment with mupirocin nasal washes in S. aureus–positive, surgically recalcitrant CRS has a high microbiological failure rate, with 73.7% of patients subsequently re‐culturing S. aureus. Our current treatment regime of 0.05% nasal washes twice daily for 4 weeks is associated with a posttreatment resistance rate that is consistent with other studies of topical mupirocin use, suggesting that mupirocin washes are no more likely to induce resistance than nasal vestibule decolonization in the high‐risk medical or surgical patient. © 2011 ARS‐AAOA, LLC.

Osteoarthritis (OA) is a degenerative disease of middle-aged and elderly people, contributed a higher burden of disease in China and the world. In 2017, under the support of the Rheumatology and Immunology Expert Committee of the Cross-Strait Medical and Health Exchange Association. The objective was to develop an evidence-based diagnosis and treatment guideline for OA in China based on emerging new evidence. The guideline was registered at International Practice Guidelines Registry Platform (IPGRP-2018CN028). The grading of recommendations assessment, development and evaluation (GRADE) approach was used to rate the quality of evidence and the strength of recommendations, and the RIGHT (Reporting Items for Practice Guidelines in Healthcare) checklist was followed to report the guideline. The guideline provides recommendations for the OA diagnosis, disease risks monitoring and evaluate, treatment purpose and physical, medical and surgical interventions. This guideline is intended to serve as a tool for Chinese clinicians for the best decisions-making on diagnosis and treatment of OA.

The UL efficacy of daily febuxostat 80 mg was greater than that of febuxostat 40 mg and allopurinol 300 mg, which exhibited comparable UL efficacy. Safety of febuxostat and allopurinol was comparable at the doses tested.

Background and PurposeAnnexin A1 (AnxA1) is an endogenous anti‐inflammatory protein and agonist of the formyl peptide receptor 2 (FPR2). However, the potential for therapeutic FPR ligands to modify immune‐mediated disease has been little explored. We investigated the effects of a synthetic FPR agonist on joint disease in the K/BxN model of rheumatoid arthritis (RA) and RA fibroblast‐like synoviocytes (FLS).Experimental ApproachArthritis was induced by injection of K/BxN serum at day 0 and 2 in wild‐type (WT) or AnxA1−/− mice and clinical and histopathological manifestations measured 8–11 days later. WT mice were given the FPR agonist compound 43 (Cpd43) (6 or 30 mg·kg−1 i.p.) for 4 days. Effects of AnxA1 and Cpd43 on RANKL‐induced osteoclastogenesis were assessed in RAW 264.7 cells and human RA FLS and macrophages.Key ResultsTreatment with Cpd43 before or after the onset of arthritis reduced clinical disease severity and attenuated synovial TNF‐α and osteoclast‐associated gene expression. Deletion of AnxA1 in mice exacerbated arthritis severity in the K/BxN model. In vitro, Cpd43 suppressed osteoclastogenesis and NFAT activity elicited by RANKL, and inhibited IL‐6 secretion by mouse macrophages. In human RA joint‐derived FLS and monocyte‐derived macrophages, Cpd43 treatment inhibited IL‐6 release, while blocking FPR2 or silencing AnxA1 increased this release.Conclusions and ImplicationsThe FPR agonist Cpd43 reduced osteoclastogenesis and inflammation in a mouse model of RA and exhibited anti‐inflammatory effects in relevant human cells. These data suggest that FPR ligands may represent novel therapeutic agents capable of ameliorating inflammation and bone damage in RA.

Intracerebral hemorrhage (ICH) can cause secondary brain damage through inflammation-related pathways. Thrombin and one of its receptors, protease activated receptor-1 (PAR-1); matrix metalloproteinase (MMP)-9; and aquaporin (AQP)-4 are stroke-related inflammatory mediators that have been implicated in ICH pathology. To further characterize the inflammatory response after ICH, we studied the temporal profile of the expression of these inflammatory mediators and assessed their potential correlation with brain edema formation after brain hemorrhage in rats. ICH was modeled by infusing autologous blood into the striatum. Then mRNA and protein expression was assessed over the course of 5 days. We found that the mRNA and/or protein expression of thrombin, PAR-1, AQP-4, and MMP-9 was upregulated between 2 h and 5 days after ICH. Each reached a maximal level at day 2, except for AQP-4 protein, which peaked at day 5. Brain water content after ICH presented a similar trend; it was increased at 2 h, peaked at day 2, and then decreased but remained elevated at day 5. Our data provide novel evidence that upregulation of these selected inflammatory mediators occurs very early and persists for several days after ICH, and that temporal patterns of expression of thrombin and AQP-4 are associated with brain edema formation. These findings have important implications for efforts to reduce secondary brain damage after ICH.

Angiogenesis is a critical factor for rheumatoid arthritis (RA). Although anti-TNF biologics work effectively on some RA patients, concerns have been raised about the possible increased development of malignancies alongside such treatments. Arsenic trioxide (As2O3) has attracted worldwide attention and has been reported to treat some cancers. However, the effects of As2O3 on angiogenesis in the RA synovium remain unclear. Here, we report a systematic increased expression of TSP-1, TGF-β1, CTGF and VEGF in supernatants of a RA fibroblast-like synoviocytes (RA-FLS) and human dermal microvascular endothelial cells (HDMECs) co-culture compared with those from a normal human fibroblast-like synoviocytes (NH-FLS) and HDMECs co-culture. This increased expression may up-regulate endothelial tube formation and transwell migration, as well as microvessel sprouting in ex vivo aortic ring assay. These networked angiogenic factors mainly form a functional module regulating angiogenesis in the RA synovium. We show that As2O3 inhibits angiogenesis in the collagen-induced arthritis (CIA) synovium and consequently arthritis severity via significant suppression of TSP-1, TGF-β1, CTGF and VEGF expression in the CIA synovium, plus in the RA-FLS and HDMECs co-culture as well as NH-FLS and HDMECs co-culture system along with the presence or absence of TNF-α treatment. Thus As2O3 has a significant anti-angiogenesis effect on the RA-FLS and CIA synovium via its inhibition of the RA angiogenic functional module of TSP-1, TGF-β1, CTGF and VEGF and may have a potential for treating RA beyond cancer therapy.

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Hypocrellin A, a peryloquinone derivative, has recently been isolated from the sacs of the fungus Hypocrella bambusae. This pigment, in combination with phototherapy, has been used in human medicine to cure various skin diseases. The generation of singlet oxygen during photoirradiation of Hypocrellin A (HA) was detected as an oxidation product of a sterically hindered amine (tetramethylpiperidine oxide; TEMPO) by electron paramagnetic resonance (EPR) spectroscopic techniques. Azide inhibited the EPR signal intensity in a dose-dependent manner with a quenching rate constant of 3.86 x 10(8) M-1s-1 in ethanol. Deuterated solvents, known to increase the lifetime of singlet oxygen, augmented the EPR signal intensity. The rate of production of singlet oxygen was dependent not only upon the concentration of HA and the time of irradiation but also on the oxygen content of the reaction mixture. The hyperfine splitting constant (aN = 16.3 G) and g-value (g = 2.0056) of the photoproduct of TEMP-singlet oxygen and TEMPO were found to be identical. This indicates that the nitroxide species detected by EPR spectroscopy generated by reacting TEMP with photogenerated 1O2 is TEMPO. The rate constant (kT) for the reaction of singlet oxygen with TEMP to form TEMPO radical was found to be 5.3 x 10(5) M-1s-1.