Effects of 4-Aminopyridine on Combined Nerve and Muscle Injury and Bone Loss.

PURPOSE: Musculoskeletal injuries are common, and peripheral nerve injury (PNI) causes significant muscle and bone loss within weeks. After PNI, 4-aminopyridine (4-AP) improves functional recovery and muscle atrophy. However, it is unknown whether 4-AP has any effect on isolated traumatic muscle injury and PNI-induced bone loss. METHODS: A standardized crush injury was performed on the sciatic nerve and muscles in mice, and the mice were assigned to receive normal saline or 4-AP treatment daily for 21 days. The postinjury motor and sensory function recovery was assessed, injured muscles were processed for histomorphometry, and the tibial bone was scanned for bone density. RESULTS: 4-Aminopyridine significantly accelerated the postinjury motor and sensory function recovery, improved muscle histomorphometry, increased muscle satellite cell numbers, and shifted muscle fiber types after combined nerve and muscle injury. Importantly, the 4-AP treatment significantly reduced PNI-induced bone loss. In contrast, in the case of isolated muscle injury, 4-AP had no effect on functional recovery and bone density, but it improved muscle-specific histomorphometry to a limited extent. CONCLUSIONS: These findings demonstrate the potential beneficial effects of 4-AP on the recovery of muscle morphology and bone density after combined muscle and nerve injury. CLINICAL RELEVANCE: Nerve injuries frequently involve muscle and result in rapid muscle and bone atrophy. In this scenario, 4-AP, in addition to accelerating nerve functional recovery, might work as an adjunctive agent to improve the recovery of injured muscle and attenuate PNI-induced bone loss.

Process Mapping Total Knee Arthroplasty: A Comparison of Instrument Designs.

BACKGROUND: Total knee arthroplasty (TKA) is commonly performed with proprietary, manual instrumentation provided by the surgical implant manufacturer. Registry studies and meta-analysis, with few outliers, have consistently shown similar functional outcomes and implant survival after TKA regardless of implant manufacturer, implant design, or surgical technique. We hypothesized that process mapping could identify areas for improvement in TKA instrumentation. METHODS: Seventeen TKA implant systems from 10 companies representing over 90% of all TKAs performed in the United States were evaluated. Instrumentation required for femoral, tibial, and patellar preparation was compared. The number of steps including surgical technician assembly steps, instrument handoffs, and surgeon steps were tabulated based off application of a standardized surgical flow, adjusted for manufacturer-recommended steps during completion of a TKA operation. RESULTS: Cruciate-retaining (CR) knee instrumentation in studied systems required 158-225 discrete steps and posterior-stabilized (PS) knees required 181-230 steps. With the fewest steps for femoral, tibial, and patellar instrumentation, CR and PS knee systems could be improved to 145 and 163 steps, respectively. The Arthrex iBalance and the Biomet Vanguard Microplasty required fewest steps among CR systems; the OrthoDevelopment Balanced and the Corin Unity required fewest steps among PS systems. CONCLUSIONS: Process mapping identified potential areas for improved instrumentation in all studied systems, suggesting the possibility to reduce operative steps broadly across the TKA industry. Patient outcomes were not evaluated by system. Future implant system design changes may do well to reduce unnecessary steps and instrumentation.