Regenerative peripheral nerve interfaces show promise to improve prosthetic rehabilitation in people with upper limb loss.

Background: Originally designed for prosthetic control, regenerative peripheral nerve interfaces (RPNIs) prevent neuroma formation by providing free muscle grafts as physiological targets for peripheral nerve ingrowth. We report the first series of patients undergoing RPNI implantation for treatment of symptomatic postamputation neuromas. Methods: A retrospective case series of all amputees undergoing RPNI implantation for treatment of symptomatic neuromas between November 2013 and June 2015 is presented. Data were obtained via chart review and phone interviews using questions derived from the Patient Reported Outcomes Measurement Information System instruments. Statistical analyses were performed using dependent sample t tests with a significance threshold of P < 0.01. Results: Forty-six RPNIs were implanted into 16 amputees for neuroma relief (3 upper extremities and 14 lower extremities). Mean age was 53.5 years (6 females and 10 males). All patients participated in postoperative phone interviews at 7.5 ± 3.4 (range: 3–15) months. Patients reported a 71% reduction in neuroma pain and a 53% reduction in phantom pain. Most patients felt satisfied or highly satisfied with RPNI surgery (75%), reporting decreased (56%) or stable (44%) levels of analgesic use. Most patients would strongly recommend RPNI surgery to a friend (88%) and would do it again if given the option (94%). Complications included delayed wound healing (n = 4) and neuroma pain at a different site (n = 2). Conclusions: RPNI implantation carries a reasonable complication profile while offering a simple, effective treatment for symptomatic neuromas. Most patients report a significant reduction in neuroma and phantom pain with a high level of satisfaction. The physiological basis for preventing neuroma recurrence is an intriguing benefit to this approach.

Objective: To identify independent predictors of 30-day venous thromboembolism (VTE) events requiring treatment after outpatient surgery. Background: An increasing proportion of surgical procedures are performed in the outpatient setting. The incidence of VTE requiring treatment after outpatient surgery is unknown. Methods: Prospective observational cohort study using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2005 to 2009. Adult patients who had outpatient surgery or surgery with subsequent 23-hour observation were included. The main outcome measure was 30-day VTE requiring treatment. Patients were randomly assigned to derivation (N = 173,501) or validation (N = 85,730) cohorts. Logistic regression examined independent risk factors for 30-day VTE. A weighted risk index was created and applied to the validation cohort. Stratified analyses examined 30-day VTE by risk level. Results: Thirty-day incidence of VTE for the overall cohort was 0.15%. Independent risk factors included current pregnancy (adjusted odds ratio [OR] = 7.80, P = 0.044), active cancer (OR = 3.66, P = 0.005), age 41 to 59 years (OR = 1.72, P = 0.008), age 60 years or more (OR = 2.48, P < 0.001), body mass index 40 kg/m² or higher (OR = 1.81, P = 0.015), operative time 120 minutes or more (OR = 1.69, P = 0.027), arthroscopic surgery (OR = 5.16, P < 0.001), saphenofemoral junction surgery (OR = 13.20, P < 0.001), and venous surgery not involving the great saphenous vein (OR = 15.61, P < 0.001). The weighted risk index identified a 20-fold variation in 30-day VTE between low (0.06%) and highest risk (1.18%) patients. Conclusions: Thirty-day VTE risk after outpatient surgery can be quantified using a weighted risk index. The risk index identifies a high-risk subgroup of patients with 30-day VTE rates of 1.18%.

Background. The purpose of this experiment was to develop a peripheral nerve interface using cultured myoblasts within a scaffold to provide a biologically stable interface while providing signal amplification for neuroprosthetic control and preventing neuroma formation.Methods. A Regenerative Peripheral Nerve Interface (RPNI) composed of a scaffold and cultured myoblasts was implanted on the end of a divided peroneal nerve in rats (n=25). The scaffold material consisted of either silicone mesh, acellular muscle, or acellular muscle with chemically polymerized poly(3,4-ethylenedioxythiophene) conductive polymer. Average implantation time was 93 days. Electrophysiological tests were performed at endpoint to determine RPNI viability and ability to transduce neural signals. Tissue samples were examined using both light microscopy and immunohistochemistry.Results. All implanted RPNIs, regardless of scaffold type, remained viable and displayed robust vascularity. Electromyographic activity and stimulated compound muscle action potentials were successfully recorded from all RPNIs. Physiologic efferent motor action potentials were detected from RPNIs in response to sensory foot stimulation. Histology and transmission electron microscopy revealed mature muscle fibers, axonal regeneration without neuroma formation, neovascularization, and synaptogenesis. Desmin staining confirmed the preservation and maturation of myoblasts within the RPNIs.Conclusions. RPNI demonstrates significant myoblast maturation, innervation, and vascularization without neuroma formation.

Patients sustaining a peripheral nerve injury will frequently experience residual muscle weakness after muscle reinnervation, even if the nerve repair is performed under optimal circumstances to allow rapid muscle reinnervation. The mechanisms responsible for this contractile dysfunction remain unclear. It is hypothesized that after peripheral nerve injury and repair, a reduced number of axons are available for skeletal muscle reinnervation that results in whole muscle force and specific force deficits. A rat model of peroneal nerve injury and repair was designed so that the number of axons available for reinnervation could be systematically reduced. In adult rats, the peroneal nerve to the extensor digitorum longus muscle was either left intact (sham group, n = 8) or divided and repaired with either 50 percent (R50 group, n = 7) or 100 percent (R100 group, n = 8) of the axons in the proximal stump included in the repair. Four months after surgery, maximal tetanic isometric force was measured and specific force was calculated for each animal. Mean tetanic isometric force for extensor digitorum longus muscles from R50 rats (2765.7 ± 767.6 mN) was significantly lower than sham (4082.8 ± 196.5 mN) and R100 (3729.0 ± 370.2 mN) rats (p < 0.003). Mean specific force calculations revealed significant deficits in both the R100 (242.1 ± 30 kN/m2) and R50 (190.6 ± 51.8 kN/m2) rats compared with the sham animals (295.9 ± 14 kN/m2) (p < 0.0005). These data support our hypothesis that after peripheral nerve injury and repair, reinnervation of skeletal muscle by a reduced number of axons results in a reduction in tetanic isometric force and specific force. The greater relative reduction in specific force compared with absolute force production after partial nerve repair may indicate that a population of residual denervated muscle fibers is responsible for this deficit.

Objective . Loss of even part of the upper limb is a devastating injury. In order to fully restore natural function when lacking sufficient residual musculature, it is necessary to record directly from peripheral nerves. However, current approaches must make trade-offs between signal quality and longevity which limit their clinical potential. To address this issue, we have developed the regenerative peripheral nerve interface (RPNI) and tested its use in non-human primates. Approach . The RPNI consists of a small, autologous partial muscle graft reinnervated by a transected peripheral nerve branch. After reinnervation, the graft acts as a bioamplifier for descending motor commands in the nerve, enabling long-term recording of high signal-to-noise ratio (SNR), functionally-specific electromyographic (EMG) signals. We implanted nine RPNIs on separate branches of the median and radial nerves in two rhesus macaques who were trained to perform cued finger movements. Main results. No adverse events were noted in either monkey, and we recorded normal EMG with high SNR (>8) from the RPNIs for up to 20 months post-implantation. Using RPNI signals recorded during the behavioral task, we were able to classify each monkey’s finger movements as flexion, extension, or rest with >96% accuracy. RPNI signals also enabled functional prosthetic control, allowing the monkeys to perform the same behavioral task equally well with either physical finger movements or RPNI-based movement classifications. Significance . The RPNI signal strength, stability, and longevity demonstrated here represents a promising method for controlling advanced prosthetic limbs and fully restoring natural movement.