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Individuals with upper limb loss lack sensation of the missing hand, which can negatively impact their daily function. Several groups have attempted to restore this sensation through electrical stimulation of residual nerves. The purpose of this study was to explore the utility of regenerative peripheral nerve interfaces (RPNIs) in eliciting referred sensation. In four participants with upper limb loss, we characterized the quality and location of sensation elicited through electrical stimulation of RPNIs over time. We also measured functional stimulation ranges (sensory perception and discomfort thresholds), sensitivity to changes in stimulation amplitude, and ability to differentiate objects of different stiffness and sizes. Over a period of up to 54 months, stimulation of RPNIs elicited sensations that were consistent in quality (e.g. tingling, kinesthesia) and were perceived in the missing hand and forearm. The location of elicited sensation was partially-stable to stable in 13 of 14 RPNIs. For 5 of 7 RPNIs tested, participants demonstrated a sensitivity to changes in stimulation amplitude, with an average just noticeable difference of 45 nC. In a case study, one participant was provided RPNI stimulation proportional to prosthetic grip force. She identified four objects of different sizes and stiffness with 56% accuracy with stimulation alone and 100% accuracy when stimulation was combined with visual feedback of hand position. Collectively, these experiments suggest that RPNIs have the potential to be used in future bi-directional prosthetic systems.

Background:. The coronavirus disease 2019 (COVID-19) pandemic required an unprecedented transformation of medical education, shifting from traditional, in-person learning to distanced, online learning. This study aimed to review changes to medical education and describe the advantages and disadvantages of virtual medical education experienced by medical students during the pandemic. Methods:. An online survey study was conducted at two medical schools, University of Michigan Medical School in the United States and Koc University School of Medicine in Turkey. Medical students completed questionnaires regarding their educational experience before and during the pandemic. Survey instruments were designed to assess differences in the educational curriculum, study methods, clinical skills self-evaluations, perceptions of the quality of in-person and online learning, and overall satisfaction. Results:. A total of 184 medical students completed the survey. There was an increase in the use of online study tools since the pandemic. There was no statistically significant difference in self-reported assessments of clinical preparedness and overall clinical competence during surgical clerkship. The percentage of students interested in pursuing a career in surgery has nearly doubled from 34% to 63%. A majority of students (83%) believed that the time available for self-study and research increased during the pandemic. Fifty-two percent of students believed that online education is less efficacious than in-person education, but 86% of students still preferred a blended approach. Conclusions:. Medical schools have continued to update their curricula following the COVID-19 pandemic. This study illustrates the transformations in medical education to ensure that the most effective and suitable teaching is delivered.

Background:. Opioid misuse after surgery remains a public health crisis in the United States. Recent efforts have focused on tracking pain medication use in surgical populations. However, accurate interpretations of medication use remain quite challenging given inconsistent usage of different datasets. The purpose of this study was to investigate the agreement between electronic medical records (EMR) versus patient self-reported use of pain medications in a surgical amputation population. Methods:. Patients undergoing major lower extremity amputation or amputation-related procedures were included in this study. Both self-reported and EMR data for pain medication intake were obtained for each patient at three time points (preoperatively, 4 months postoperatively, and 12 months postoperatively). Percentage agreement and the kappa statistic were calculated for both usage (yes/no) and dose categories. Results:. Forty-five patients were included in this study, resulting in 108 pairs of self-reported and EMR datasets. Substantial levels of agreement (>70% agreement, kappa >0.61) for opioid use was seen at preoperative and 12 months postoperative. However, agreement dropped at 4 months postoperatively. Anticonvulsant medication showed high levels, whereas acetaminophen showed lower levels of agreements at all time points. Conclusions:. Either self-reported or EMR data may be used in research and clinical settings for preoperative or 12-month postoperative patients with little concern for discrepancies. However, at time points immediately following the expected end of acute surgical pain, self-reported data may be needed for more accurate medication reporting. With these findings in mind, usage of datasets should be driven by study objectives and the dataset’s strength (eg, accuracy, ease, lack of bias).

Summary:. Regenerative peripheral nerve interface (RPNI) surgery has been demonstrated to be an effective tool as an interface for neuroprosthetics. Additionally, it has been shown to be a reproducible and reliable strategy for the active treatment and for prevention of neuromas. The purpose of this article is to provide a comprehensive review of RPNI surgery to demonstrate its simplicity and empower reconstructive surgeons to add this to their armamentarium. This article discusses the basic science of neuroma formation and prevention, as well as the theory of RPNI. An anatomic review and discussion of surgical technique for each level of amputation and considerations for other etiologies of traumatic neuromas are included. Lastly, the authors discuss the future of RPNI surgery and compare this with other active techniques for the treatment of neuromas.

Soft tissue trauma can result in aberrant osteochondral differentiation of local mesenchymal progenitor cells. Here the authors show that, in mice, soft tissue trauma results in NGF expression by perivascular cells, which leads to axonal invasion and drives abnormal osteochondral differentiation, and show that this process can be prevented by inhibition of NGF signaling.

Background:. Despite advancements in surgical and rehabilitation strategies, extremity amputations are frequently associated with disability, phantom limb sensations, and chronic pain. Investigation into potential treatment modalities has focused on the pathophysiological changes in both the peripheral and central nervous systems to better understand the underlying mechanism in the development of chronic pain in persons with amputations. Methods:. Presented in this article is a discussion outlining the physiological changes that occur in the peripheral and central nervous systems following amputation. In this review, the authors examine the molecular and neuroplastic changes occurring in the nervous system, as well as the state-of-the-art treatment to help reduce the development of postamputation pain. Results:. This review summarizes the current literature regarding neurological changes following amputation. Development of both central sensitization and neuronal remodeling in the spinal cord and cerebral cortex allows for the development of neuropathic and phantom limb pain postamputation. Recently developed treatments targeting these pathophysiological changes have enabled a reduction in the severity of pain; however, complete resolution remains elusive. Conclusions:. Changes in the peripheral and central nervous systems following amputation should not be viewed as separate pathologies, but rather two interdependent mechanisms that underlie the development of pathological pain. A better understanding of the physiological changes following amputation will allow for improvements in therapeutic treatments to minimize pathological pain caused by amputation.

Regenerative Peripheral Nerve Interface represents a surgical technique, whereby a free muscle graft is utilized as a physiological ‘target’ for peripheral nerve ingrowth. This procedure was first developed for increasing the amplitude of motor nerve signals to control neuro-prosthetic devices. Regenerative Peripheral Nerve Interface has since been broadened for painful stump neuroma management in amputees, in addition to further optimizing advances in neuro-prosthetic function. To the best of our knowledge, this paper presents two cases, with the first documented use of Regenerative Peripheral Nerve Interface, as an innovative technique for the management of iatrogenic, symptomatic neuroma in-continuity complications involving the forefoot.

Summary:. Systemic scleroderma is a chronic connective tissue disease characterized by internal organ and skin fibrosis. Unfortunately, there is a lack of efficacious treatments for cutaneous manifestations, and alternative interventions should be considered. Fat grafting has gained significant attention due to its regenerative properties and success in improving skin quality and volume deficits in fibrotic diseases. While some studies have investigated the efficacy of autologous fat grafting, we utilized the Coleman method for harvesting and processing to determine the efficacy of fat grafting to improve skin fibrosis in the hands and face of scleroderma patients without excess processing of adipose tissue. Patients with a diagnosis of scleroderma who underwent fat grafting between March 2015 and March 2019 at the University of Michigan were included. Ten female patients were identified that met inclusion criteria. The mean age at the time of surgery was 48.7 (± 17.6) years. An average of 53.2 (± 15.5) ml of fat was injected into the hands and 26.1 (± 16.4) ml into the face. Patients were treated with 1–4 rounds of grafting depending on the initial severity of skin fibrosis and volume deficiency. Fat grafting subjectively and qualitatively improved perioral skin quality, facial animation, hand range of motion, and hand pain for patients with systemic scleroderma. No complications were identified. Additional studies are necessary to determine the ideal volume, timing of treatments, and type of fat to optimize the efficacy of autologous fat grafting for the treatment of systemic scleroderma.

Summary:. The Coronavirus Disease 2019 (COVID-19) pandemic has presented a major threat to public health worldwide alongside unprecedented global economic and social implications. In the absence of a “gold standard” treatment, the rapid development of a safe and effective vaccine is considered the most promising way to control the pandemic. In recent years, traditional vaccine technologies have seemed insufficient to provide global protection against the rapid spread of emerging pandemics. Therefore, the establishment of novel approaches that are independent of whole pathogen cultivation, cost-effective, and able to be rapidly developed and produced on a large scale are of paramount importance for global health. This article summarizes the current efforts to develop a COVID-19 vaccine, including the ongoing and future anticipated clinical trials. We also provide plastic and reconstructive surgeons with insight into the novel technologies currently utilized for COVID-19 vaccine development, focusing on the very promising viral-vector-based and gene-based vaccine technologies. Each platform has its own advantages and disadvantages related to its efficacy and ability to induce certain immune responses, manufacturing capacity, and safety for human use. Once the fundamental key challenges have been addressed for viral-vector-based and gene-based vaccines, these novel technologies may become helpful in winning the fight against COVID-19 and transforming the future of health care.

Summary:. Painful neuromas result from traumatic injuries of the hand and digits and cause substantial physical disability, psychological distress, and decreased quality of life among affected patients. The regenerative peripheral nerve interface (RPNI) is a novel surgical technique that involves implanting the divided end of a peripheral nerve into a free muscle graft for the purposes of mitigating neuroma formation and facilitating prosthetic limb control. The RPNI is effective in treating and preventing neuroma pain in major extremity amputations. The purpose of this study was to determine if RPNIs can be used to effectively treat neuroma pain following partial hand and digital amputations. We retrospectively reviewed the use of RPNI to treat symptomatic hand and digital neuromas at our institutions. Between November 2014 and July 2019, we performed 30 therapeutic RPNIs on 14 symptomatic neuroma patients. The average patient follow-up was 37 weeks (6–128 weeks); 85% of patients were pain-free or considerably improved at the last office visit. The RPNI can serve as a safe and effective surgical solution to treat symptomatic neuromas after hand trauma.

Abstract Introduction Regenerative peripheral nerve interfaces (RPNIs) are biological constructs which amplify neural signals and have shown long-term stability in rat models. Real-time control of a neuroprosthesis in rat models has not yet been demonstrated. The purpose of this study was to: a) design and validate a system for translating electromyography (EMG) signals from an RPNI in a rat model into real-time control of a neuroprosthetic hand, and; b) use the system to demonstrate RPNI proportional neuroprosthesis control. Methods Animals were randomly assigned to three experimental groups: (1) Control; (2) Denervated, and; (3) RPNI. In the RPNI group, the extensor digitorum longus (EDL) muscle was dissected free, denervated, transferred to the lateral thigh and neurotized with the residual end of the transected common peroneal nerve. Rats received tactile stimuli to the hind-limb via monofilaments, and electrodes were used to record EMG. Signals were filtered, rectified and integrated using a moving sample window. Processed EMG signals (iEMG) from RPNIs were validated against Control and Denervated group outputs. Results Voluntary reflexive rat movements produced signaling that activated the prosthesis in both the Control and RPNI groups, but produced no activation in the Denervated group. Signal-to-Noise ratio between hind-limb movement and resting iEMG was 3.55 for Controls and 3.81 for RPNIs. Both Control and RPNI groups exhibited a logarithmic iEMG increase with increased monofilament pressure, allowing graded prosthetic hand speed control (R2 = 0.758 and R2 = 0.802, respectively). Conclusion EMG signals were successfully acquired from RPNIs and translated into real-time neuroprosthetic control. Signal contamination from muscles adjacent to the RPNI was minimal. RPNI constructs provided reliable proportional prosthetic hand control.

Abstract Background The role of the kidney in glucose homeostasis has gained global interest. Kidneys are innervated by renal nerves, and renal denervation animal models have shown improved glucose regulation. We hypothesized that stimulation of renal nerves at kilohertz frequencies, which can block propagation of action potentials, would increase urine glucose excretion. Conversely, we hypothesized that low frequency stimulation, which has been shown to increase renal nerve activity, would decrease urine glucose excretion. Methods We performed non-survival experiments on male rats under thiobutabarbital anesthesia. A cuff electrode was placed around the left renal artery, encircling the renal nerves. Ureters were cannulated bilaterally to obtain urine samples from each kidney independently for comparison. Renal nerves were stimulated at kilohertz frequencies (1–50 kHz) or low frequencies (2–5 Hz), with intravenous administration of a glucose bolus shortly into the 25–40-min stimulation period. Urine samples were collected at 5–10-min intervals, and colorimetric assays were used to quantify glucose excretion and concentration between stimulated and non-stimulated kidneys. A Kruskal-Wallis test was performed across all stimulation frequencies (α = 0.05), followed by a post-hoc Wilcoxon rank sum test with Bonferroni correction (α = 0.005). Results For kilohertz frequency trials, the stimulated kidney yielded a higher average total urine glucose excretion at 33 kHz (+ 24.5%; n = 9) than 1 kHz (− 5.9%; n = 6) and 50 kHz (+ 2.3%; n = 14). In low frequency stimulation trials, 5 Hz stimulation led to a lower average total urine glucose excretion (− 40.4%; n = 6) than 2 Hz (− 27.2%; n = 5). The average total urine glucose excretion between 33 kHz and 5 Hz was statistically significant (p

Purpose: Although advanced prosthetic devices have the potential to allow fine-motor movements and extract somatosensory signals via sensitive pressure sensors, an ideal interface to integrate the human nervous system with the prosthetic doesn’t exist. Furthermore, the requirement for the implantation of indwelling electrodes and prohibitive costs limits the application of current technologies. The Regenerative Peripheral Nerve Interface (RPNI) was developed as a stable biologic interface on the notion of providing physiologic end-organ targets for regenerating axons by implantation of a residual nerve into an autogenous free muscle graft. Despite providing intuitive motor control, RPNI sensory feedback is limited and also relies on implantable electrodes for myoelectric signal transmission. To address these challenges, we investigated the placement of RPNIs underneath the defatted skin in rats to capture myoelectric signals using surface electrodes. This strategy simultaneously provides sensory feedback through the sensory reinnervation of the overlying skin. Methods: Utilizing six male F344 rats, the right tibial nerve was transected distally in the thigh before entering the leg’s posterior compartment. Subsequently, the left side extensor digitorum longus (EDL) muscle was harvested and co-apted with the proximal segment of the tibial nerve for RPNI fabrication. The RPNI was placed and secured in between the biceps femoris muscle near the skin while the side opposite to the nerve coaptation was facing the dermis. The overlying skin was defatted and fixed on top of the superficial RPNI (S-RPNI). At two months post-surgery, functional motor reinnervation was evaluated by electrical stimulation of the tibial nerve and compound muscle action potentials (CMAPs) were recorded using surface electrodes. Sensory feedback was assessed by electrical and mechanical stimulation of the skin to respectively record sensory nerve action potentials (SNAPs) and sensory afferent signals. The S-RPNI construct and its overlying skin were subsequently harvested and processed for immunohistochemistry and whole-mount immunostaining. Results: Recording muscle CMAPs from the skin was readily feasible in all animals, showing robust signals with minimal noise distortion (366 µV ± 86.3). Electrical stimulation of the skin on the lateral thigh, which is not innervated by the tibial nerve normally, resulted in classic tri-phasic SNAP generation in this nerve. Brushing the overlying skin using a cotton swab generated synchronized monomorphic afferent signals. Sensory reinnervation of the skin was shown using IHC. Whole-mount staining of the muscle component showed regenerated muscle with new neuromuscular junctions (NMJs) and spatial segregation of sensory fibers toward their end-target organ. Conclusion: Superficially placed RPNI is a viable and an alternate methodology that is simple to implicate and has the potential to transmit simultaneous, real-time, and independent sensory and motor signals between the residual nerve and the prostheses.

Background:. Lymphedema is a debilitating condition characterized by swelling from lymph fluid exceeding transport capacity. A gold standard for arm measurement is not established, and measurement methods vary. This study evaluates the comparability of the tape measure and Analytic Morphomics in deriving limb circumference measurements in patients with upper extremity lymphedema. Methods:. Fifteen participants with diagnosed upper limb lymphedema were included between July 2013 and June 2017 at Chang Gung Memorial Hospital in Taipei, Taiwan. Affected and unaffected arm circumferences were measured using a flexible tape or morphomic measurement at 10 cm above and below the elbow. Computed tomography scans were standardized, processed, smoothed with a piecewise polynomial algorithm for Analytic Morphomics of arm circumference. Comparative plots, mean percent difference, and adjusted coefficient of determination (R2) were utilized to compare the consistency of both measurement procedures. Results:. The tape measure and Analytic Morphomics demonstrated consistent measures of arm circumference. On the affected arm, the mean (95% CI) difference in arm circumference between methods was 1.60 cm (0.99–2.20) above, and 0.57 cm (0.23–0.91) below the elbow. Mean percent differences in circumference was 6.65% (SD 3.52%) above and 1.38% (SD 2.11%) below the elbow. The adjusted R2 for both methods was 94% above and 96% below the elbow. Conclusions:. Analytic Morphomics showed strong consistency with the manual tape measure of arm circumference measurement in those with upper extremity lymphedema. Analytic Morphomics present an opportunity for a precise, granular measurement of limb composition for assessment of disease state and patient planning.

Background:. Many insurance carriers continue to deny coverage for reduction mammaplasty unless a minimum amount of resected breast tissue per breast is achieved during surgery. This study investigates the accuracy of preoperative prediction that a minimum weight of 500 g can be resected and evaluates potential risk factors for not meeting this insurance requirement. Methods:. A retrospective review was performed on 445 patients with bilateral symptomatic macromastia who sought consultation for breast reduction surgery from 2007 to 2012. Women were included for analysis if they had documented predicted resection weights and underwent small-to-moderate breast reduction (< 1,000 g per side; n = 323). Relevant demographic information, mean predicted resection weight, and the mean actual resection weight were collected for analysis. Results:. Surgeon prediction of resection weight being over 500 g had a positive predictive value of 73%. In 61 patients (19%), the predicted weights were ≥ 500 g, but the actual weights were < 500 g. Thirty percentage of these 61 patients did not meet either Schnur or minimum weight requirements. Women with a body mass index < 30 were at significantly increased odds (odds ratio, 3.76; 95% confidence interval, 1.89–7.48; P = 0.002) of not meeting the minimum weight requirement at surgery compared with patients with a body mass index ≥ 30. Conclusions:. The common insurance criterion of removing ≥ 500 g per breast during breast reduction surgery are not met in a distinct cohort of women who are clinically appropriate candidates. This risk is particularly increased in nonobese women possibly due to proportionately smaller breast mass compared with obese women.