Palliative arthroscopic debridement with continuous irrigation for infected total knee arthroplasty in high mortality risk patients.

PURPOSE: This study aimed to evaluate the infection control rate of palliative arthroscopic debridement, antibiotics, and implant retention (DAIR) for the high mortality risk or terminal cancer stage patients. METHODS: From March 2018 to August 2021, 21 patients met the following inclusion criteria: old age of more than 80, diagnosed as a terminal stage of cancer, high risk of mortality and morbidity representing as Charlson comorbidity index (CCI) ≥ 5, low daily activity with disabled extremity, and re-infection after two-stage revision. Each patient underwent arthroscopic DAIR and additional continuous irrigation for 48 hours. The need for subsequent re-arthroscopic DAIR or two-stage revision was determined by the post-operative trends of C-reactive protein (CRP) levels. Infection control was defined as continuing controlled status of infection based on clinical and laboratory results by one or two times of arthroscopic DAIR within initial two months. Treatment failure was defined as more than three times arthroscopic debridement, two-stage revision surgery, or expired due to uncontrolled infection. RESULTS: Arthroscopic DAIR controlled the infection in 19 (90.5%) of the 21 cases. The other knee underwent a total of three times of re-arthroscopic DAIR and the other one underwent two-stage revision. Although five patients expired during the follow-up period due to worsening medical problems or terminal cancer, there were no deaths from uncontrolled infection, sepsis, or surgery-related complications. CONCLUSIONS: Arthroscopic debridement with continuous irrigation for the infection TKA with high mortality risk or terminal cancer patients showed a 90.5% infection control rate. For high-risk patients, arthroscopic debridement with continuous irrigation can be an alternative treatment to improve the quality of life during survival.

Caffeic acid, morin hydrate and quercetin partially attenuate sulfur mustard-induced cell death by inhibiting the lipoxygenase pathway.

Sulfur mustard (SM) is an alkylating agent, which has been used as in chemical warfare in a number of conflicts. As the generation of reactive oxygen species (ROS), and adducts in DNA and proteins have been suggested as the mechanism underlying SM­induced cytotoxicity, the present study screened several antioxidant candidates, including tannic acid, deferoxamine mesylate, trolox, vitamin C, ellagic acid and caffeic acid (CA) to assess their potential as therapeutic agents for SM­induced cell death. Among several antioxidants, CA partially alleviated SM­induced cell death in a dose­dependent manner. Although CA treatment decreased the phosphorylation of p38 mitogen­activated protein (MAP) kinase and p53, p38 MAP kinase inhibition by SB203580 did not affect SM­induced cell death. As CA has also been reported as a 15­lipoxygenase (15­LOX) inhibitor, the role of 15­LOX in SM­induced cytotoxicity was also examined. Similar to the results observed with CA, treatment with PD146176, a specific 15­LOX inhibitor, decreased SM­induced cytotoxicity, accompanied by decreases in the production of tumor necrosis factor­α and 15­hydroxyeicosatetraenoic acid. Furthermore, the present study investigated the protective effects of two natural 15­LOX inhibitors, morin hydrate and quercetin, in SM­induced cytotoxicity. As expected, these inhibitors had similar protective effects against SM­induced cytotoxicity. These antioxidants also reduced the generation of ROS and nitrate/nitrite. Therefore, the results of the present study indicated that the natural products, CA, quercetin and morin hydrate, offer potential as adjuvant therapeutic agents for SM­induced toxicity, not only by reducing inflammation mediated by the p38 and LOX signaling pathways, but also by decreasing the generation of ROS and nitrate/nitrite.

Characterisation of insulin-producing cells differentiated from tonsil derived mesenchymal stem cells.

Tonsil-derived (T-) mesenchymal stem cells (MSCs) display mutilineage differentiation potential and self-renewal capacity and have potential as a banking source. Diabetes mellitus is a prevalent disease in modern society, and the transplantation of pancreatic progenitor cells or various stem cell-derived insulin-secreting cells has been suggested as a novel therapy for diabetes. The potential of T-MSCs to trans-differentiate into pancreatic progenitor cells or insulin-secreting cells has not yet been investigated. We examined the potential of human T-MSCs to trans-differentiate into pancreatic islet cells using two different methods based on ß-mercaptoethanol and insulin-transferin-selenium, respectively. First, we compared the efficacy of the two methods for inducing differentiation into insulin-producing cells. We demonstrated that the insulin-transferin-selenium method is more efficient for inducing differentiation into insulin-secreting cells regardless of the source of the MSCs. Second, we compared the differentiation potential of two different MSC types: T-MSCs and adipose-derived MSCs (A-MSCs). T-MSCs had a differentiation capacity similar to that of A-MSCs and were capable of secreting insulin in response to glucose concentration. Islet-like clusters differentiated from T-MSCs had lower synaptotagmin-3, -5, -7, and -8 levels, and consequently lower secreted insulin levels than cells differentiated from A-MSCs. These results imply that T-MSCs can differentiate into functional pancreatic islet-like cells and could provide a novel, alternative cell therapy for diabetes mellitus.

Effects of a tetramethoxyhydroxyflavone p7f on the expression of inflammatory mediators in LPS-treated human synovial fibroblast and macrophage cells.

The inhibitory effects of 5,6,3',5'-tetramethoxy 7,4'-hydroxyflavone (labeled as p7F) were elucidated on the productions of proinflammatory cytokines as well as inflammatory mediators in human synovial fibroblasts and macrophage cells. p7F inhibited IL-1beta or TNF-alpha induced expressions of inflammatory mediators (ICAM-1, COX-2, and iNOS). p7F also inhibited LPS-induced productions of nitric oxide and prostaglandin E2 in RAW 264.7 cells. In order to investigate whether p7F would inhibit IL-1 signaling, p7F was added to the D10S Th2 cell line (which is responsive to only IL-1beta and thus proliferates), revealing that p7F inhibited IL-1beta-induced proliferation of D10S Th2 cells in a doseresponse manner. A flow cytometric analysis revealed that p7F reduced the intracellular level of free radical oxygen species in RAW 264.7 cells treated with hydrogen peroxide. p7F inhibited IkappaB degradation and NF-kappaB activation in macrophage cells treated with LPS, supporting that p7F could inhibit signaling mediated via toll-like receptor. Taken together, p7F has inhibitory effects on LPS-induced productions of inflammatory mediators on human synovial fibroblasts and macrophage cells and thus has the potential to be an antiinflammatory agent for inhibiting inflammatory responses.