Osteoarthritis (OA) is a chronic disability that significantly impairs quality of life. OA is one of the most prevalent joint pathologies in the world, characterized by joint pain and stiffness due to the degeneration of articular cartilage and the remodeling of subchondral bone. OA pathogenesis is unique in that it involves simultaneous reparative and degradative mechanisms. Low-grade inflammation as opposed to high-grade allows for this coexistence. Previously, macrophages and T cells have been identified as playing major roles in the inflammation and destruction of OA joints, but recent studies have demonstrated that neutrophils also contribute to the pathogenesis. Neutrophils are the first immune cells to enter the synovium after joint injury, and neutrophilic activity is indispensably a requisite for the progression of OA. Neutrophils act through multiple mechanisms including tissue degeneration via neutrophil elastase (NE), osteophyte development, and the release of inflammatory cytokines and chemokines. As the actions of neutrophils in OA are discovered, the potential for novel therapeutic targets as well as diagnostic methods are revealed. The use of chondrogenic progenitor cells (CPCs), microRNAs, and exosomes are among the newest therapeutic advances in OA treatment, and this review reveals how they can be used to mitigate destructive neutrophil activity.
Background There is not a prevailing consensus on appropriate antibiotic choice, route, and duration in the treatment of bacterial pleural empyema after appropriate source control. Professional society guidelines note the lack of comparative trials with which to guide recommendations. We assessed clinical outcomes in the treatment of known and suspected empyema based upon three aspects of antibiotic use: (1) total duration, (2) duration of intravenous (IV) antibiotics, and (3) duration of anti-anaerobic antibiotics. Methods We performed a hypothesis-generating retrospective chart review analysis of 355 adult inpatients who had pleural drainage, via either chest tube or surgical intervention, for known or suspected empyema. The primary outcome variable was clinician assessment of resolution or lack thereof. The secondary outcomes were death within 90 days, hospital readmission within 30 days for empyema, and all-cause hospital readmission within 30 days. Mann-Whitney U test was used to compare outcomes with regard to these variables. Results None of the independent variables was significantly associated with a difference in clinical resolution rate despite trends for total antibiotic duration and anti-anaerobic antibiotic duration. None of the independent variables was associated with mortality. Longer total antibiotic duration was associated with lower readmission rate for empyema (median 17 [interquartile range 11–28] antibiotic days in non-readmission group vs. 13 [6-15] days in readmission group), with a non-significant trend for all-cause readmission rate (17 [11–28] days vs. 14 [9–21] days). IV antibiotic duration was not associated with a difference in any of the defined outcomes. Longer duration of anti-anaerobic antibiotics was associated with both lower all-cause readmission (8.5 [0–17] vs. 2 [0–11]) and lower readmission rate for empyema (8 [0–17] vs. 2 [0–3]). Conclusion Our data support the premise that routine use of anti-anaerobic antibiotics is indicated in the treatment of pleural empyema. However, our study casts doubt on the benefits of extended IV rather than oral antibiotics in the treatment of empyema. This represents a target for future investigation that could potentially limit complications associated with the excessive use of IV antibiotics.
Structured Abstract Objectives Skeletal stem cells (SSCs) are characterized by expression of cell surface biomarkers and their ability to differentiate into bone, cartilage and fat. However, the current biomarkers used to identify these cell populations are not cell‐type‐specific or indicative of the differentiation status of these cells and are therefore unreliable. Our objective was to identify alternative cell surface biomarkers and transcription factors shared between SSCs isolated from the bone marrow (BM) and those derived from pluripotent stem cells (PSC). Materials and Methods Human PSCs were induced into SSCs. FACS and qRT‐PCR were used to determine differences in expression of cell surface biomarkers and transcription factors between SSCs derived from PSCs and isolated from BM, in differentiating cells, in cells from early and late passage, and in fibroblasts. Results A significant reduction in proliferation and capacity of SSCs to differentiate into adipocytes and osteoblasts was observed after 3 passages. Protein and mRNA analysis indicated that commonly used biomarkers remain highly expressed in cells that lost capacity for differentiation. However, integrin α6 (CD49f) and transcription factors GATA6, PRDM16, SIM2 and SOX11 were significantly upregulated in SSCs compared to fibroblasts. In early stages of adipogenic and osteogenic differentiation, the expression of CD49f, GATA6 and SIM2 was reduced in later passage cells, which have limited proliferation and differentiation capabilities. Conclusions Our results suggest that CD49f and transcription factors GATA6 and SIM2 identify functional SSCs.
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