Systematic Review and Meta-Analysis of Global Neuroma Incidence in Upper Extremity Amputees.

BACKGROUND: Neuromas substantially decrease a patient's quality of life and obstruct the use of prosthetics. This systematic review and meta-analysis aimed to determine the global incidence of neuroma formation in upper extremity amputees. METHODS: A literature search was performed using 3 databases: Web of Science, MEDLINE, and Cochrane. Inclusion criteria for the systematic review were those studies investigating only upper extremity amputees and reported postamputation neuroma. A random-effects, inverse-variance analysis was conducted to determine the pooled proportion of neuromas within the upper extremity amputation population. Critical appraisal using the JBI Checklist for Studies Reporting Prevalence Data of each individual article were performed for the systematic review. RESULTS: Eleven studies met the inclusion criteria collating a total of 1931 patients across 8 countries. More than three-fourth of patients are young men (77%; age range, 19-54 years) and had an amputation due to trauma. The random-effects analysis found the pooled combined proportion of neuromas to be 13% (95% confidence interval, 8%-18%). The treatment of neuroma is highly variable, with some patients receiving no treatment. CONCLUSIONS: The pooled proportion of neuroma incidence in the 1931 patients was 13%. With the known global prevalence of upper extremity amputees, this translates to nearly 3 million amputees suffering from a neuroma globally. Increasing training in preventative surgical methods could contribute to lowering this incidence and improving the outcomes of this patient population.

Timing of Autologous Tissue Breast Reconstruction Does Not Affect Free Flap Failure.

ABSTRACT: This study aimed to determine whether there is a difference in free flap failure based on the decision to undergo immediate versus delayed autologous tissue breast reconstruction after mastectomy. The National Surgical Quality Improvement Program database was queried for breast free flap procedures performed between 2015 and 2020. This study demonstrates that the decision to undergo immediate versus delayed autologous tissue breast reconstruction does not have a significant association with free flap failure. This remains true regardless of whether patients undergo unilateral mastectomy with reconstruction or whether patients choose to also undergo contralateral prophylactic mastectomy with reconstruction.

Reduced Access to Acute Hand Care and Potential Role of Telemedicine in Tennessee During the COVID Pandemic.

INTRODUCTION: Previous studies have identified that there is limited, although expanding, access to acute hand care in Tennessee. Because of the rapid changes that occurred in health delivery and access during the coronavirus disease pandemic, we reassessed access to acute hand care, with particular interest in the utilization of telemedicine to assess if this increased access. METHOD: We surveyed Tennessee hospitals listed by the Tennessee Hospital Association on their management of hand trauma and availability of telemedicine programs. Census data including population demographics such as race, age, income, and county size were merged with the survey data. Descriptive analysis was performed comparing the 2021 cohort with the historic 2018 cohort and between counties that had hand care versus counties that had no hand care. RESULT: Survey response rate was 71.4% (n = 80 of 112). Telemedicine was used in 80% of the hospitals for other specialties but was not used for hand care. Overall, counties that offered hand trauma care reduced from 60% to 26% from 2018 to 2021 ( P < 0.001). This change was associated with a significant reduction of acute hand care among counties that were classified micropolitan (from 56.3% to 6.7%, P < 0.01). Percentage of hand specialists on staff and 24/7 specialists availability remained low and were similar to the availability in 2018. CONCLUSIONS: There was a decrease of acute hand care access in Tennessee during the coronavirus disease pandemic despite widespread utilization of telemedicine for other specialty consults. Expansion of telemedicine in acute hand care, targeted to micropolitan areas, may help to reduce variability in access to care.

Amputated Digit Replantations: Critical Digit Ischemia Timing, Temperature, and Other Predictors of Survival.

INTRODUCTION: A common consideration for replantation success is the ischemia time following injury and the preservation temperature. A classic principle within the hand surgery community describes 12 hours of warm ischemia and 24 hours of cold ischemia as the upper limits for digit replantation; however, these limits are largely anecdotal and based on older studies. We aimed to compare survival data from the large body of literature to aid surgeons and all those involved in the replantation process in hopes of optimizing success rates. METHODS: The PubMed database was queried on April 4th, 2023, for articles that included data on digit replantation survival in terms of temperature of preservation and ischemia time. All primary outcomes were analyzed with the Mantel-Haenszel method within a random effects model. Secondary outcomes were pooled and analyzed using the chi-square statistic. Statistical analysis and forest plot generation were completed with RevMan 5.4 software with odds ratios calculated within a 95% confidence interval. RESULTS: Our meta-analysis identified that digits preserved in cold ischemia for over 12 hours had significantly higher odds of replantation success than the amputated digits replanted with 0-12 hours of warm ischemia time ( P ≤ 0.05). The odds of survival in the early (0-6 hours) replantation group were around 40% greater than the later (6-12 hours) replantation group ( P ≤ 0.05). Secondary outcomes that were associated with higher survival rates included a clean-cut amputation, increased venous and arterial anastomosis, a repair that did not require a vein graft, and replants performed in nonsmokers ( P ≤ 0.05). DISCUSSION: Overall, these findings suggest that when predicting digit replantation success, time is of the essence when the digit has yet to be preserved in a cold environment. This benefit, however, is almost completely diminished when the amputated digit is appropriately maintained in a cold environment soon after injury. In conclusion, our results suggest that there is potential for broadening the ischemia time limits for digit replant survival outlined in the literature, particularly for digits that have been stored correctly in cold ischemia.

Delayed Versus Immediate Breast Reconstruction in the Ambulatory Surgery Setting: A Cross-Sectional Analysis of the Nationwide Ambulatory Surgery Sample.

BACKGROUND: Breast reconstruction remains an important part of a patient's journey after the diagnosis of breast carcinoma and treatment with mastectomy. Although inpatient immediate breast reconstruction has been described, there is a paucity information about whether similar procedures are performed in the ambulatory setting. OBJECTIVE: The authors sought to investigate rates and patterns for delayed and immediate breast reconstruction in the ambulatory surgery setting using nationally representative data from 2016 to 2019. METHODS: Using the Nationwide Ambulatory Surgery Sample database, we identified patients with an International Statistical Classification of Disease and Related Health Problems, Tenth Revision, procedure code for breast reconstruction. Demographic and clinical characteristics were recorded for each encounter of breast reconstruction, and linear regression and logistic regression were used to assess for trends and disparities. RESULTS: National weighted estimates for ambulatory breast reconstruction increased by 15.6% from 89 237 in 2016 to 103 134 in 2019, resulting in 377 109 procedures during the study period. Inflation-adjusted total charges for ambulatory breast reconstruction were $14 billion between 2016 and 2019, or 1.7% of overall charges for ambulatory surgery. Immediate reconstruction was performed in 34.7% (95% CI, 33.4%-36.1%) of cases and increased by 46.9% from 26 930 in 2016 to 39 559 in 2019. Racial disparities were observed in access, comorbidities, and spending. CONCLUSIONS: Our findings indicate a moderate increase in ambulatory breast reconstruction with a substantial growth in the performance of immediate breast reconstruction in the ambulatory setting.

Effect of a Perioperative Educational Video in Patients Undergoing Mohs Reconstruction: A Randomized Clinical Trial.

BACKGROUND: Skin cancer is the most common type of cancer in the United States, and most are treated with Mohs micrographic surgery (MMS) by fellowship-trained dermatologic surgeons. Complex reconstruction in cosmetically and functionally sensitive areas often requires a plastic surgery consult. The uncertainty regarding reconstructive options and cosmetic appearance is difficult emotionally and cognitively for patients. OBJECTIVES: To improve patient understanding about MMS reconstruction with plastic surgeons, we investigated the utility of a multimedia presentation during perioperative education. METHODS: A randomized clinical trial was conducted at a hospital-affiliated outpatient MMS clinic and surgery center in the United States. Patients in the intervention arm were given a tablet or Web site link to watch a multimedia presentation about reconstruction after MMS. All patients were given a questionnaire about their understanding of MMS reconstruction and satisfaction with the reconstructive care they received. RESULTS: A total of 46 patients were recruited for the study and completed the questionnaire. Of these patients, 22 were randomized to the test intervention arm, and the remaining 24 were in the control group. Among participants in the test intervention arm, feedback regarding the platform was positive with more than 90% of patients reporting that the video was engaging, useful, and easy to understand. Patient understanding and satisfaction scores in the test intervention arm ranked higher across all domains than those of the control group. CONCLUSIONS: This randomized clinical trial showed increases in patient understanding and satisfaction among patients undergoing MMS reconstruction with the implementation of a perioperative educational video.

Pulmonary Embolism Risk After Cosmetic Abdominoplasty and Functional Panniculectomy.

BACKGROUND: Tighter abdominal wall reconstruction may increase intra-abdominal pressure, which can decrease lower extremity venous return. Decreased venous return through the inferior vena cava has been demonstrated to increase risk of deep vein thrombosis. OBJECTIVES: Tighter abdominal wall plication during cosmetic abdominoplasty compared with functional panniculectomy may increase these risks. The purpose of this study was to determine whether cosmetic abdominoplasty increases risk for thromboembolic events compared with functional panniculectomy. METHODS: Retrospective cohort study was conducted using the National Surgical Quality Improvement Program database for excision of excessive subcutaneous infraumbilical skin and soft tissue at participating hospitals between 2015 and 2019. Procedures performed for cosmetic abdominoplasty versus functional panniculectomy were compared for occurrences of postoperative pulmonary embolism (PE). RESULTS: During the study interval, 11,137 patients underwent excision of excessive infraumbilical abdominal skin, including 57.4% (n = 6397) patients undergoing functional panniculectomy and 42.6% (n = 4740) patients undergoing cosmetic abdominoplasty. Patients undergoing functional panniculectomy were significantly more likely to have comorbidities than those undergoing cosmetic abdominoplasty ( P < 0.001). The risk for postoperative PE was independently associated with cosmetic abdominoplasty ( P < 0.001), elevated body mass index ( P = 0.001), preoperative recent weight loss ( P = 0.006), and concurrent hernia repair ( P = 0.049). Most PE events occurred outpatient after discharge (87.2%), and the average postoperative time from surgery until PE was 10.5 ± 6.7 days. CONCLUSIONS: Cosmetic abdominoplasty has greater than 4 times the risk of postoperative PE than functional panniculectomy. Risk of PE is further increased by concurrent hernia repair, elevated body mass index, and rapid weight loss in the immediate preoperative period. It may be advisable to caution patients to delay abdominal excisional body contouring procedures until their weight has plateaued.

Breast Reconstruction Free Flap Failure: Does Platelet Count Matter?

BACKGROUND: Microvascular free tissue transfer is an increasingly popular modality for autologous tissue breast reconstruction. However, flap failure remains an ominous risk that continues to plague surgeons and patients even in the setting of meticulous surgical technique and monitoring. Venous and arterial thromboses are the leading causes of free flap failure. The purpose of this study was to determine whether thrombocytosis is associated with breast free flap failure. METHODS: A retrospective study was conducted of breast reconstruction with free flaps in North America between 2015 and 2020 using the National Surgical Quality Improvement Program database. Patient comorbidities and preoperative laboratory tests were used to determine risk factors for free flap failure. RESULTS: During the study interval, 7522 female patients underwent breast reconstruction with free flaps, and flap failure occurred in 2.7% patients (n = 203). In multivariate regression analysis, breast free flap failure was significantly higher in patients smoking cigarettes within the past year (P = 0.030; AOR, 1.7) and dyspnea on moderate exertion or at rest (P = 0.025; AOR, 2.6). Furthermore, each 50 K/mcL elevation in platelet count was independently associated with an increased odds of flap failure (P < 0.001; AOR, 1.2). Patients experienced significantly higher rates of flap failure with platelet counts greater than 250 K/mcL (P = 0.004), which remained significant through progressively increasing thresholds up to 450 K/mcL. CONCLUSIONS: Platelet count greater than 250 K/mcL is associated with progressively increasing risk of free flap failure in breast reconstruction. Future studies of personalized patient anticoagulation protocols based on hemostatic metrics may improve free flap survival after autologous tissue breast reconstruction.

Anatomic Comparison of Recipient Nerves for Deep Inferior Epigastric Perforator Flap Neurotization: A Randomized Control Trial.

INTRODUCTION: Although neurotization has the potential to improve sensory outcomes after autologous breast reconstruction, this technique remains controversial. There is debate regarding the clinical outcomes and the recipient nerve of choice. This histoanatomical study aims to quantitatively compare the sensory components of the recipient nerves involved in neurotization of the deep inferior epigastric perforator flap. METHODS: Subjects undergoing bilateral autologous breast reconstruction were enrolled. Transected nerve specimens underwent immunohistochemical staining with antibodies against neurofilament 1 and choline acetyltransferase for total and motor neurons within the axons, respectively. Photomicrographs were captured, and axons were analyzed using ImageJ. Sensory axons were calculated as equal to the difference between the total and cholinergic axonal counts. RESULTS: Thirty-eight nerves from 19 subjects were included. The overall mean sensory axon count was 1246.3 (±1171.9) in the lateral cutaneous branch (LCB) of the fourth intercostal nerve and 1123.8 (±1213.0) in the anterior cutaneous branch (ACB) of the third intercostal nerve.The fourth LCB presented with an additional 10.9% sensory axonal count (P > 0.05). On average, sensory fibers constituted 36.7% and 31.7% of all fibers in the third ACBs and fourth LCBs, respectively. CONCLUSIONS: This study provides anatomic and histological evidence that the fourth LCB and third ACB contain comparable mean numbers of sensory axons. Both constitute adequate recipient nerves for coaptation in deep inferior epigastric perforator reinnervation to achieve optimal sensory return after breast reconstruction. The fourth LCB should be preferable when the third ACB remains intact to preserve any native breast flap sensation.

A Systematic Review and Meta-analysis on the Incidence of Patients With Lower-Limb Amputations Who Developed Symptomatic Neuromata in the Residual Limb.

BACKGROUND: Neuromata developed after major extremity amputation can cause pain, limit the use of prosthetics, and negatively affect the quality of life. The frequency of postamputation neuroma varies widely. The objective of this study was to determine the incidence of patients who developed symptomatic neuromata after lower-limb amputation through a systematic review and meta-analysis. METHODS: A systematic review of the literature was performed on 4 major databases. Studies that reported the incidence of symptomatic neuroma in lower-limb amputees were included. A meta-analysis was performed to calculate the pooled incidence of neuromata. RESULTS: Thirteen studies consisting of 1329 patients were included in this meta-analysis. The reported incidence of patients who developed symptomatic neuromata ranged between 4% and 49%. The median duration of follow-up was 8.6 years (interquartile range, 2.0-17.4 years). The pooled percentage (95% confidence interval [CI]) of lower-limb amputees who developed symptomatic neuromata was 19% (12%-29%). In studies with a duration of follow-up at least 3 years, the pooled percentage (95% CI) of lower-limb amputees who developed symptomatic neuromata was 30% (22%-40%). In studies with a follow-up period of fewer than 3 years, the pooled percentage (95% CI) of neuroma incidence was 3% (2%-6%). CONCLUSIONS: In summary, the overall incidence of patients who developed symptomatic neuromata was 19% or approximately 1 in 5 lower-limb amputees. Symptomatic neuromata are more commonly diagnosed when the follow-up period is longer than 3 years. These findings suggest that neuroma after amputation might be underestimated in studies with a short duration of follow-up.

Peripheral nerve repair throughout the body with processed nerve allografts: Results from a large multicenter study.

BACKGROUND: Peripheral nerve damage resulting in pain, loss of sensation, or motor function may necessitate a reconstruction with a bridging material. The RANGER® Registry was designed to evaluate outcomes following nerve repair with processed nerve allograft (Avance® Nerve Graft; Axogen; Alachua, FL). Here we report on the results from the largest peripheral nerve registry to-date. METHODS: This multicenter IRB-approved registry study collected data from patients repaired with processed nerve allograft (PNA). Sites followed their own standard of care for patient treatment and follow-up. Data were assessed for meaningful recovery, defined as ≥S3/M3 to remain consistent with previously published results, and comparisons were made to reference literature. RESULTS: The study included 385 subjects and 624 nerve repairs. Overall, 82% meaningful recovery (MR) was achieved across sensory, mixed, and motor nerve repairs up to gaps of 70 mm. No related adverse events were reported. There were no significant differences in MR across the nerve type, age, time-to-repair, and smoking status subgroups in the upper extremity (p > .05). Significant differences were noted by the mechanism of injury subgroups between complex injures (74%) as compared to lacerations (85%) or neuroma resections (94%) (p = .03) and by gap length between the <15 mm and 50-70 mm gap subgroups, 91 and 69% MR, respectively (p = .01). Results were comparable to historical literature for nerve autograft and exceed that of conduit. CONCLUSIONS: These findings provide clinical evidence to support the continued use of PNA up to 70 mm in sensory, mixed and motor nerve repair throughout the body and across a broad patient population.

An Evaluation of Emergency Hand Coverage in Tennessee After Implementation of the Affordable Care Act.

Although the upper extremity is the most commonly injured part of the body, many studies have indicated that there is a lack of emergency hand coverage in the United States. In 2010, our laboratory evaluated on-call hand coverage in Tennessee (TN) and found that only 7% of hospitals had a hand surgeon on call for emergency cases at all times. In 2014, the Affordable Care Act (ACA) was implemented with the goal of increasing overall access to care and decreasing health care costs. Hand surgeons were surveyed on their attitudes toward the ACA, and the majority of surgeons surveyed disagreed or strongly disagree that the ACA would improve access to emergent hand surgery. This study aimed to determine if there has been an increase in emergency hand coverage in TN since the implementation of the ACA. A survey was administered to all hospitals in TN with both an emergency department and operating room to determine the percentage of TN hospitals offering elective hand surgery and on-call emergency hand coverage. With 94% of TN hospitals responding to the emergency department survey, we determined that there has been a 138% significant increase in the percentage of hospitals reporting 24/7 emergency hand coverage by a hand specialist since our last study in 2010. There has also been a significant increase in elective hand coverage in TN, although much smaller at 13% since 2010. This study suggests that there has been an overall increase in access to hand care in TN since the implementation of the ACA, most profoundly seen in the increase in hand specialists available for emergent cases.

Comparing Processed Nerve Allografts and Assessing Their Capacity to Retain and Release Nerve Growth Factor.

Peripheral nerve gap injuries continue to present a clinical challenge to today's surgeons. One method of surgical repair, implantation of acellular allografts, has been developed with the aim of bridging the gap with a cadaveric graft after removal of its cellular components, thereby accelerating axonal regeneration and eliminating the need for immunosuppression in recipient patients. Although decellularizing allografts reduces rates of graft rejection, the same chemical processing modifies the neural microenvironment, removing neutrotrophic factors and modifying the complex extracellular matrix. In this study, we explore 3 common methods for producing acellular allografts. Extracellular matrix content remaining after processing was investigated and was found to be highly dependent on the decellularization method. In addition, scanning electron micrographs were obtained to evaluate the structural effects of the decellularization methods. Though the content and structure of these processed allografts will contribute to their effectiveness as nerve gap repair candidates, we demonstrate that it also affects their capacity to be supplemented/preloaded with the prototypical neurotrophin, nerve growth factor (NGF), essential to neuronal regeneration. Although all allografts had some capacity for retaining NGF in the first 24 hours, only Sondell-processed grafts retained NGF over the entire experimental period of 21 days. Future studies will include validating these processed and supplemented allografts as viable alternatives to traditional autograft nerve gap repair.

Assessment of the Effect of Autograft Orientation on Peripheral Nerve Regeneration Using Diffusion Tensor Imaging.

PURPOSE: Given no definite consensus on the accepted autograft orientation during peripheral nerve injury repair, we compare outcomes between reverse and normally oriented autografts using an advanced magnetic resonance imaging technique, diffusion tensor imaging. METHODS: Thirty-six female Sprague-Dawley rats were divided into 3 groups: sham-left sciatic nerve isolation without injury, reverse autograft-10-mm cut left sciatic nerve segment reoriented 180° and used to coapt the proximal and distal stumps, or normally oriented autograft-10-mm cut nerve segment kept in its normal orientation for coaptation. Animals underwent sciatic functional index and foot fault behavior studies at 72 hours, and then weekly. At 6 weeks, axons proximal, within, and distal to the autograft were evaluated using diffusion tensor imaging and choline acetyltransferase motor staining for immunohistochemistry. Toluidine blue staining of 1-µm sections was used to assess axon count, density, and diameter. Bilateral gastrocnemius/soleus muscle weights were compared to obtain a net wet weight. Comparison of the groups was performed using Mann-Whiney U or Kruskal-Wallis H tests to determine significance. RESULTS: Diffusion tensor imaging findings including fractional anisotropy, radial diffusivity, and axial diffusivity were similar between reverse and normally oriented autografts. Diffusion tensor imaging tractography demonstrated proximodistal nerve regeneration in both autograft groups. Motor axon counts proximal, within, and distal to the autografts were similar. Likewise, axon count, density, and diameter were similar between the autograft groups. Muscle net weight at 6 weeks and behavioral outcomes (sciatic functional index and foot fault) at any tested time point were also similar between reverse and normally oriented autografts. CONCLUSIONS: Diffusion tensor imaging may be a useful assessment tool for peripheral nerve regeneration. Reversing nerve autograft polarity did not demonstrate to have an influence on functional or regenerative outcomes.

A novel conduit-based coaptation device for primary nerve repair.

BACKGROUND: Conduit-based nerve repairs are commonly used for small nerve gaps, whereas primary repair may be performed if there is no tension on nerve endings. We hypothesize that a conduit-based nerve coaptation device will improve nerve repair outcomes by avoiding sutures at the nerve repair site and utilizing the advantages of a conduit-based repair. METHODS: The left sciatic nerves of female Sprague-Dawley rats were transected and repaired using a novel conduit-based device. The conduit-based device group was compared to a control group of rats that underwent a standard end-to-end microsurgical repair of the sciatic nerve. Animals underwent behavioral assessments at weekly intervals post-operatively using the sciatic functional index (SFI) test. Animals were sacrificed at four weeks to obtain motor axon counts from immunohistochemistry. A sub-group of animals were sacrificed immediately post repair to obtain MRI images. RESULTS: SFI scores were superior in rats which received conduit-based repairs compared to the control group. Motor axon counts distal to the injury in the device group at four weeks were statistically superior to the control group. MRI tractography was used to demonstrate repair of two nerves using the novel conduit device. CONCLUSIONS: A conduit-based nerve coaptation device avoids sutures at the nerve repair site and leads to improved outcomes in a rat model. Conduit-based nerve repair devices have the potential to standardize nerve repairs while improving outcomes.

Evaluation of a Nerve Fusion Technique With Polyethylene Glycol in a Delayed Setting After Nerve Injury.

PURPOSE: Polyethylene glycol (PEG) has been hypothesized to restore axonal continuity using an in vivo rat sciatic nerve injury model when nerve repair occurs within minutes after nerve injury. We hypothesized that PEG could restore axonal continuity when nerve repair was delayed. METHODS: The left sciatic nerves of female Sprague-Dawley rats were transected and repaired in an end-to-end fashion using standard microsurgical techniques at 3 time points (1, 8, and 24 hours) after injury. Polyethylene glycol was delivered to the neurorrhaphy in the experimental group. Post-repair compound action potentials were immediately recorded after repair. Animals underwent behavioral assessments at 3 days and 1 week after surgery using the sciatic functional index test. The animals were sacrificed at 1 week to obtain axon counts. RESULTS: The PEG-treated nerves had improved compound action potential conduction and animals treated with PEG had improved sciatic function index. Compound action potential conduction was restored in PEG-fused rats when nerves were repaired at 1, 8, and 24 hours. In the control groups, no compound action potential conduction was restored when nerves were repaired. Sciatic functional index was superior in PEG-fused rats at 3 and 7 days after surgery compared with control groups at all 3 time points of nerve repair. Distal motor and sensory axon counts were higher in the PEG-treated rats. CONCLUSIONS: Polyethylene glycol fusion is a new adjunct for nerve repair that allows rapid restoration of axonal continuity. It effective when delayed nerve repair is performed. CLINICAL RELEVANCE: Nerve repair with application of PEG is a potential therapy that may have efficacy in a clinical setting. It is an experimental therapy that needs more investigation as well as clinical trials.

Mass spectrometry comparison of nerve allograft decellularization processes.

Peripheral nerve repair using nerve grafts has been investigated for several decades using traditional techniques such as histology, immunohistochemistry, and electron microscopy. Recent advances in mass spectrometry techniques have made it possible to study the proteomes of complex tissues, including extracellular matrix rich tissues similar to peripheral nerves. The present study comparatively assessed three previously described processing methods for generating acellular nerve grafts by mass spectrometry. Acellular nerve grafts were additionally examined by F-actin staining and nuclear staining for debris clearance. Application of newer techniques allowed us to detect and highlight differences among the 3 treatments. Isolated proteins were separated by mass on polyacrylamide gels serving 2 purposes. This further illustrated that these treatments differ from one another and it allowed for selective protein extractions within specific bands/molecular weights. This approach resulted in small pools of proteins that could then be analyzed by mass spectrometry for content. In total, 543 proteins were identified, many of which corroborate previous findings for these processing methods. The remaining proteins are novel discoveries that expand the field. With this pilot study, we have proven that mass spectrometry techniques complement and add value to peripheral nerve repair studies.

Bridging the Gap: Engineered Porcine-derived Urinary Bladder Matrix Conduits as a Novel Scaffold for Peripheral Nerve Regeneration.

PURPOSE: This study aims to compare engineered nerve conduits constructed from porcine-derived urinary bladder matrix (UBM) with the criterion-standard nerve autografts, for segmental loss peripheral nerve repairs. METHODS: Forty-eight Sprague-Dawley rats were divided into 2 groups. All underwent a 10-mm sciatic nerve gap injury. This was repaired using either (1) reverse autograft-the 10-mm cut segment was oriented 180 degrees and used to coapt the proximal and distal stumps or (2) UBM conduit-the 10-mm nerve gap was bridged with UBM conduit. Behavior assessments such as sciatic function index and foot fault asymmetry scores were performed weekly. At 3- or 6-week time endpoints, the repaired nerves and bilateral gastrocnemius/soleus muscles were harvested from each animal. Nerves were evaluated using immunohistochemistry for motor and sensory axon staining and with diffusion tensor imaging. The net wet muscle weights were calculated to assess the degree of muscle atrophy. RESULTS: The UBM group demonstrated significantly improved foot fault asymmetry scores at 2 and 4 weeks, whereas there was no difference in sciatic function index. The net muscle weights were similar between both groups. Motor axon counts proximal/inside/distal to the conduit/graft were similar between UBM conduits and reverse autografts, whereas sensory axon counts within and distal to the conduit were significantly higher than those of the autograft at 6 weeks. Sensory axonal regeneration seemed to be adherent to the inner surface of the UBM conduit, whereas it had a scattered appearance in autografts. Diffusion tensor imaging parameters between groups were similar. CONCLUSIONS: Urinary bladder matrix conduits prove to be at least similar to nerve autografts for the repair of peripheral nerve injuries with a short gap. The matrix perhaps serves as a scaffold to augment sensory nerve growth. CLINICAL RELEVANCE: In a clinical setting, UBM may eliminate the donor site morbidity and increased operative time associated with nerve autografting.

Immediate Enhancement of Nerve Function Using a Novel Axonal Fusion Device After Neurotmesis.

BACKGROUND: The management of peripheral nerve injuries remains a large challenge for plastic surgeons. With the inability to fuse axonal endings, results after microsurgical nerve repair have been inconsistent. Our current nerve repair strategies rely upon the slow and lengthy process of axonal regeneration (~1 mm/d). Polyethylene glycol (PEG) has been investigated as a potential axonal fusion agent; however, the percentage of axonal fusion has been inconsistent. The purpose of this study was to identify a PEG delivery device to standardize outcomes after attempted axonal fusion with PEG. MATERIALS AND METHODS: We used a rat sciatic nerve injury model in which we completely transected and repaired the left sciatic nerve to evaluate the efficacy of PEG fusion over a span of 12 weeks. In addition, we evaluated the effectiveness of a delivery device's ability to optimize results after PEG fusion. RESULTS: We found that PEG rapidly (within minutes) restores axonal continuity as assessed by electrophysiology, fluorescent retrograde tracer, and diffusion tensor imaging. Immunohistochemical analysis shows that motor axon counts are significantly increased at 1 week, 4 weeks, and 12 weeks postoperatively in PEG-treated animals. Furthermore, PEG restored behavioral functions up to 50% compared with animals that received the criterion standard epineurial repair (control animals). CONCLUSIONS: The ability of PEG to rapidly restore nerve function after neurotmesis could have vast implications on the clinical management of traumatic injuries to peripheral nerves.

Effects of extracellular calcium and surgical techniques on restoration of axonal continuity by polyethylene glycol fusion following complete cut or crush severance of rat sciatic nerves.

Complete crush or cut severance of sciatic nerve axons in rats and other mammals produces immediate loss of axonal continuity. Loss of locomotor functions subserved by those axons is restored only after months, if ever, by outgrowths regenerating at ∼1 mm/day from the proximal stumps of severed axonal segments. The distal stump of a severed axon typically begins to degenerate in 1-3 days. We recently developed a polyethylene glycol (PEG) fusion technology, consisting of sequential exposure of severed axonal ends to hypotonic Ca(2+) -free saline, methylene blue, PEG in distilled water, and finally Ca(2+) -containing isotonic saline. This study examines factors that affect the PEG fusion restoration of axonal continuity within minutes, as measured by conduction of action potentials and diffusion of an intracellular fluorescent dye across the lesion site of rat sciatic nerves completely cut or crush severed in the midthigh. Also examined are factors that affect the longer-term PEG fusion restoration of lost behavioral functions within days to weeks, as measured by the sciatic functional index. We report that exposure of cut-severed axonal ends to Ca(2+) -containing saline prior to PEG fusion and stretch/tension of proximal or distal axonal segments of cut-severed axons decrease PEG fusion success. Conversely, trimming cut-severed ends in Ca(2+) -free saline just prior to PEG fusion increases PEG fusion success. PEG fusion prevents or retards the Wallerian degeneration of cut-severed axons, as assessed by measures of axon diameter and G ratio. PEG fusion may produce a paradigm shift in the treatment of peripheral nerve injuries. © 2016 Wiley Periodicals, Inc.