Injectable Fibrin/Polyethylene Oxide Semi-IPN Hydrogel for a Segmental Meniscal Defect Regeneration.

BACKGROUND: Meniscal deficiency from meniscectomy is a common situation in clinical practices. Regeneration of the deficient meniscal portion, however, is still not feasible. PURPOSE: To develop an injectable hydrogel system consisting of fibrin (Fb) and polyethylene oxide (PEO) and to estimate its clinical potential for treating a segmental defect of the meniscus in a rabbit meniscal defect model. STUDY DESIGN: Controlled laboratory study. METHODS: The Fb/PEO hydrogel was fabricated by extruding 100 mg·mL-1 of fibrinogen solution and 2,500 U·mL-1 of thrombin solution containing 100 mg·mL-1 of PEO through a dual-syringe system. The hydrogels were characterized by rheological analysis and biodegradation tests. The meniscal defects of New Zealand White male rabbits were generated by removing 60% of the medial meniscus from the anterior side. The removed portion included the central portion. The Fb/PEO hydrogel was injected into the meniscal defect of the experimental knee through the joint space between the femoral condyle and tibial plateau at the anterior knee without a skin incision. The entire medial menisci from both knees of each rabbit were collected and photographed before placement in formalin for histological processing. Hematoxylin and eosin, safranin O, and immunohistochemical staining for type II collagen was performed. The biomechanical property of the regenerated meniscus was evaluated using a universal tensile machine. RESULTS: The Fb/PEO hydrogel was fabricated by an in situ gelation process, and the hydrogel displayed a semi-interpenetrating polymer network structure. We demonstrated that the mechanical properties of Fb-based hydrogels increased in a PEO-dependent manner. Furthermore, the addition of PEO delayed the biodegradation of the hydrogel. Our in vivo data demonstrated that, as compared with Fb hydrogel, Fb/PEO hydrogel injection into the meniscectomy model showed improved tissue regeneration. The regenerated meniscal tissue by Fb/PEO hydrogel showed enhanced tissue quality, which was supported by the histological and biomechanical properties. CONCLUSION: The Fb/PEO hydrogel had an effective tissue-regenerative ability through injection into the in vivo rabbit meniscal defect model. CLINICAL RELEVANCE: This injectable hydrogel system can promote meniscal repair and be readily utilized in clinical application.

Femoral nerve block for patient undergoing total knee arthroplasty: Prospective, randomized, double-blinded study evaluating analgesic effect of perineural fentanyl additive to local anesthetics.

BACKGROUND: The existence of peripheral opioid receptors and its effectiveness in peripheral nerve block remain controversial. The aim of this prospective, randomized, double-blinded study was to examine the analgesic effects of adding fentanyl to ropivacaine for continuous femoral nerve block (CFNB) using patient-controlled analgesia after total knee arthroplasty (TKA). METHODS: The patients were divided into 2 groups, each with n = 40 in ropivacaine (R) group and n = 42 in R with fentanyl (R + F) group. After operation, the patients in each group received R + F and R alone via a femoral nerve catheter, respectively. We assessed the visual analog scale (VAS) pain immediately before administration (baseline) and at 15, 30, and 60 minutes on postanesthesia care unit (PACU), and resting and ambulatory VAS score up to 24 hours. RESULTS: Overall, the average VAS scores in the R + F group were slightly lower than those of the R group. However, the VAS score differences between groups were not statistically significant, except for 30 minutes (P = 0.009) in PACU. R group showed higher supplemental analgesics consumption in average compared with R + F group, but not significant. CONCLUSION: Additional fentanyl did not show prominent enhancement of analgesic effect in the field of CFNB after TKA.

Stearoyl lysophosphatidylcholine enhances the phagocytic ability of macrophages through the AMP-activated protein kinase/p38 mitogen activated protein kinase pathway.

A previous study showed that stearoyl lysophosphatidylcholine (sLPC) suppressed extracellular high mobility group box 1 translocation in macrophages stimulated with lipopolysaccharide through AMP-activated protein kinase (AMPK) activation. In the present study, we investigated whether sLPC-induced AMPK activation could enhance macrophages phagocytosis of bacteria. We found that sLPC increased phosphorylation of AMPK and acetyl-CoA carboxylase, a downstream target of AMPK, in a time- and dose-dependent manner in macrophages. Furthermore, sLPC increased the uptake of FITC-conjugated Escherichia coli by macrophages in a dose-dependent manner, and treatment with an AMPK inhibitor (compound C) or siRNA to AMPKα1 reversed this uptake. sLPC increased the phosphorylation of p38 mitogen-activated protein kinase (MAPK), but inhibition of AMPK activity with compound C or siRNA to AMPKα1 prevented the sLPC-induced increase in p38 MAPK phosphorylation. SB203580, a p38 MAPK inhibitor, decreased sLPC-induced phagocytosis. In vivo, systemic administration of sLPC to mice led to increased AMPK and p38 MAPK activity in the lung and to increased phagocytosis of fluorescent E. coli in bronchoalveolar lavage cells. These results suggest that sLPC increases macrophages phagocytosis through activation of the AMPK/p38 MAPK pathway. Therefore, sLPC is a candidate pharmacological agent for the treatment of bacterial infections in clinically relevant conditions.

Effect of Immunotherapy on Seizure Outcome in Patients with Autoimmune Encephalitis: A Prospective Observational Registry Study.

OBJECTIVE: To evaluate the seizure characteristics and outcome after immunotherapy in adult patients with autoimmune encephalitis (AE) and new-onset seizure. METHODS: Adult (age ≥18 years) patients with AE and new-onset seizure who underwent immunotherapy and were followed-up for at least 6 months were included. Seizure frequency was evaluated at 2-4 weeks and 6 months after the onset of the initial immunotherapy and was categorized as "seizure remission", "> 50% seizure reduction", or "no change" based on the degree of its decrease. RESULTS: Forty-one AE patients who presented with new-onset seizure were analysed. At 2-4 weeks after the initial immunotherapy, 51.2% of the patients were seizure free, and 24.4% had significant seizure reduction. At 6 months, seizure remission was observed in 73.2% of the patients, although four patients died during hospitalization. Rituximab was used as a second-line immunotherapy in 12 patients who continued to have seizures despite the initial immunotherapy, and additional seizure remission was achieved in 66.6% of them. In particular, those who exhibited partial response to the initial immunotherapy had a better seizure outcome after rituximab, with low adverse events. CONCLUSION: AE frequently presented as seizure, but only 18.9% of the living patients suffered from seizure at 6 months after immunotherapy. Aggressive immunotherapy can improve seizure outcome in patients with AE.