Crosstalk between CD4 T cells and synovial fibroblasts from human arthritic joints promotes hyaluronan-dependent leukocyte adhesion and inflammatory cytokine expression in vitro.

The content and organization of hyaluronan (HA) in the extracellular matrix (ECM) have been identified as strong indicators of inflammation in joint disease, although the source and role of HA as an effector of inflammation is not clear. In this study, we established co-cultures of activated human CD4 T cells with fibroblast-like synoviocytes (FLS) from osteoarthritis (OA) and rheumatoid arthritis (RA) subjects and examined the role of HA in promoting inflammatory events. Co-cultures of RA FLS with activated CD4 T cells generated an HA-enriched ECM that promoted enhanced monocyte adhesion compared to co-cultures of OA FLS with activated CD4 T cells. In addition, both OA FLS and RA FLS co-cultures with activated CD4 T cells elicited significant increases in the expression of IL1ß, TNF, and IL6, with the increase in IL6 expression most prominent in RA co-cultures. Blocking HA synthesis and accumulation with 4-methylumbelliferone reduced expression of IL6, IL1ß, and TNF in both OA FLS and RA FLS co-cultures. The increase in HA synthesis in the co-cultures was mimicked by IL6 trans-signaling of FLS in the absence of CD4 T cells. Inhibition of HA synthesis blocked the increase in IL6 by RA FLS mediated by IL6 trans-signaling, suggesting that the HA synthetic pathway may be a key mediator in IL6 expression by FLS. Overall, our study indicates that HA-enriched ECM generated by co-cultures of activated CD4 T cells with FLS from human joints creates a pathogenic microenvironment by promoting adhesion of leukocytes and expression of inflammatory cytokines including IL6.

MRI and muscle enzymes do not support the diagnosis of local anesthetic myotoxicity: a descriptive case series.

BACKGROUND: The presence of thigh muscle edema as characterized by increased signal intensity on MRI has been used to support the diagnosis of presumed local anesthetic-induced myotoxicity reported after total knee arthroplasty (TKA) with continuous adductor canal block (CACB). However, neither postoperative baseline imaging appearance nor muscle enzyme values have been described in conjunction with this clinical scenario. Thus, the usefulness of MRI or enzymatic biomarkers of muscle injury for supporting the diagnosis of local anesthetic myotoxicity is unknown. METHODS: This descriptive case series documents postoperative MRI appearance of the ipsilateral upper leg, plus preoperative and postoperative creatine phosphokinase and aldolase values in volunteer patients who underwent uncomplicated TKA with CACB. RESULTS: In 27 volunteer patients with no postsurgical evidence of clinically relevant myotoxicity, anterior thigh muscle edema was universally evident on imaging (n=12) and muscle enzyme values (n=19) were normal or only slightly elevated. CONCLUSIONS: The non-specificity of these findings suggests that MRI and near normal muscle enzyme levels are of limited diagnostic value when there is clinical suspicion of local anesthetic myotoxicity in the setting of TKA with CACB. TRIAL REGISTRATION NUMBER: NCT04821245.

Reduced Length of Hospitalization in Primary Total Knee Arthroplasty Patients Using an Updated Enhanced Recovery After Orthopedic Surgery (ERAS) Pathway.

Decreasing hospital length of stay may attenuate costs associated with total knee arthroplasty. The purpose of this study was to determine if updates to an existing orthopedic enhanced recovery after surgery (ERAS) pathway would improve length of hospitalization. Clinical and demographic data were collected on 252 primary total knee arthroplasties between January 2012 and July 2013. Pre-updated and post-updated ERAS pathway cohorts were analyzed for length of stay, clinical outcomes, and re-admissions. The mean length of stay decreased from 76.6 hours to 56.1 hours after implementation of the evidence-based orthopedic enhanced recovery after surgery pathway (P<0.001). This improvement was possible without a concomitant increase in readmission rates.

Exaggerated inflammatory response after use of recombinant bone morphogenetic protein in recurrent unicameral bone cysts.

BACKGROUND: Recurrent unicameral bone cysts (UBCs) can result in significant morbidity during a child's physical and emotional development. Multiple treatment options are available and a review of the literature fails to clearly define the optimal treatment for UBCs. Recombinant bone morphogenetic protein (BMP) has been used with success in other disorders of poor bone formation. This manuscript is the first to report on the use of recombinant BMP in the treatment of UBCs. METHODS: Three patients with recurrent UBCs underwent revision surgery with recombinant BMP. Radiographic and medical review was performed and is reported here. RESULTS: In these patients, the use of BMP failed to fully resolve their UBC; 2 patients had complete recurrence that required further surgery. In addition to poor radiographic results, all patients developed exaggerated inflammatory responses in the acute postoperative period. Each child developed clinically significant limb swelling and pain that mimicked infection. CONCLUSIONS: On the basis of our poor radiographic results and a paradoxical clinical result, we no longer recommend the use of recombinant BMP in the manner reported here for the treatment of recurrent UBCs. LEVEL OF EVIDENCE: Level IV, case series.