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.

Recovery of Motor Function after Mixed and Motor Nerve Repair with Processed Nerve Allograft.

BACKGROUND: Severe trauma often results in the transection of major peripheral nerves. The RANGER Registry is an ongoing observational study on the use and outcomes of processed nerve allografts (PNAs; Avance Nerve Graft, AxoGen, Inc., Alachua, Fla.). Here, we report on motor recovery outcomes for nerve injuries repaired acutely or in a delayed fashion with PNA and comparisons to historical controls in the literature. METHODS: The RANGER database was queried for mixed and motor nerve injuries in the upper extremities, head, and neck area having completed greater than 1 year of follow-up. All subjects with sufficient assessments to evaluate functional outcomes were included. Meaningful recovery was defined as ≥M3 on the Medical Research Council scale. Demographics, outcomes, and covariate analysis were performed to further characterize this subgroup. RESULTS: The subgroup included 20 subjects with 22 nerve repairs. The mean ± SD (minimum-maximum) age was 38 ± 19 (16-77) years. The median repair time was 9 (0-133) days. The mean graft length was 33 ± 17 (10-70) mm with a mean follow-up of 779 ± 480 (371-2,423) days. Meaningful motor recovery was observed in 73%. Subgroup analysis showed no differences between gap lengths or mechanism of injury. There were no related adverse events. CONCLUSIONS: PNAs were safe and provided functional motor recovery in mixed and motor nerve repairs. Outcomes compare favorably to historical controls for nerve autograft and exceed those for hollow tube conduit. PNA may be considered as an option when reconstructing major peripheral nerve injuries.

Use of Processed Nerve Allografts to Repair Nerve Injuries Greater Than 25 mm in the Hand.

Processed nerve allografts (PNAs) have been demonstrated to have improved clinical results compared with hollow conduits for reconstruction of digital nerve gaps less than 25 mm; however, the use of PNAs for longer gaps warrants further clinical investigation. Long nerve gaps have been traditionally hard to study because of low incidence. The advent of the RANGER registry, a large, institutional review board-approved, active database for PNA (Avance Nerve Graft; AxoGen, Inc, Alachua, FL) has allowed evaluation of lower incidence subsets. The RANGER database was queried for digital nerve repairs of 25 mm or greater. Demographics, injury, treatment, and functional outcomes were recorded on standardized forms. Patients younger than 18 and those lacking quantitative follow-up data were excluded. Recovery was graded according to the Medical Research Council Classification for sensory function, with meaningful recovery defined as S3 or greater level. Fifty digital nerve injuries in 28 subjects were included. There were 22 male and 6 female subjects, and the mean age was 45. Three patients gave a previous history of diabetes, and there were 6 active smokers. The most commonly reported mechanisms of injury were saw injuries (n = 13), crushing injuries (n = 9), resection of neuroma (n = 9), amputation/avulsions (n = 8), sharp lacerations (n = 7), and blast/gunshots (n = 4). The average gap length was 35 ± 8 mm (range, 25-50 mm). Recovery to the S3 or greater level was reported in 86% of repairs. Static 2-point discrimination (s2PD) and Semmes-Weinstein monofilament (SWF) were the most common completed assessments. Mean s2PD in 24 repairs reporting 2PD data was 9 ± 4 mm. For the 38 repairs with SWF data, protective sensation was reported in 33 repairs, deep pressure in 2, and no recovery in 3. These data compared favorably with historical data for nerve autograft repairs, with reported levels of meaningful recovery of 60% to 88%. There were no reported adverse effects. Processed nerve allograft can be used to reconstruct long gap nerve defects in the hand with consistently high rates of meaningful recovery. Results for PNA repairs of digital nerve injuries with gaps longer than 25 mm compare favorably with historical reports for nerve autograft repair but without donor site morbidity.

Functional outcome following nerve repair in the upper extremity using processed nerve allograft.

PURPOSE: Reconstruction of peripheral nerve discontinuities with processed nerve allograft has become increasingly relevant. The RANGER Study registry was initiated in 2007 to study the use of processed nerve allografts in contemporary clinical practice. We undertook this study to analyze outcomes for upper extremity nerve repairs contained in the registry database. METHODS: We identified an upper extremity-specific population within the RANGER Study registry database consisting of 71 nerves repaired with processed nerve allograft. This group was composed of 56 subjects with a mean age of 40 ± 17 years (range, 18-86 y). We analyzed data to determine the safety and efficacy of processed nerve allograft. Quantitative data were available on 51 subjects with 35 sensory, 13 mixed, and 3 motor nerves. The mean gap length was 23 ± 12 mm (range, 5-50 mm). We performed an analysis to evaluate response-to-treatment and to examine sensory and motor recovery according to the international standards for motor and sensory nerve recovery. RESULTS: There were no reported implant complications, tissue rejections, or adverse experiences related to the use of the processed nerve allografts. Overall recovery, S3 or M4 and above, was achieved in 86% of the procedures. Subgroup analysis demonstrated meaningful levels of recovery in sensory, mixed, and motor nerve repairs with graft lengths between 5 and 50 mm. The study also found meaningful levels of recovery in 89% of digital nerve repairs, 75% of median nerve repairs, and 67% of ulnar nerve repairs. CONCLUSIONS: Our data suggest that processed nerve allografts offer a safe and effective method of reconstructing peripheral nerve gaps from 5 to 50 mm in length. These outcomes compare favorably with those reported in the literature for nerve autograft, and exceed those reported for tube conduits.

Processed nerve allografts for peripheral nerve reconstruction: a multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions.

PURPOSE: As alternatives to autograft become more conventional, clinical outcomes data on their effectiveness in restoring meaningful function is essential. In this study we report on the outcomes from a multicenter study on processed nerve allografts (Avance® Nerve Graft, AxoGen, Inc). PATIENTS AND METHODS: Twelve sites with 25 surgeons contributed data from 132 individual nerve injuries. Data was analyzed to determine the safety and efficacy of the nerve allograft. Sufficient data for efficacy analysis were reported in 76 injuries (49 sensory, 18 mixed, and 9 motor nerves). The mean age was 41 ± 17 (18-86) years. The mean graft length was 22 ± 11 (5-50) mm. Subgroup analysis was performed to determine the relationship to factors known to influence outcomes of nerve repair such as nerve type, gap length, patient age, time to repair, age of injury, and mechanism of injury. RESULTS: Meaningful recovery was reported in 87% of the repairs reporting quantitative data. Subgroup analysis demonstrated consistency, showing no significant differences with regard to recovery outcomes between the groups (P > 0.05 Fisher's Exact Test). No graft related adverse experiences were reported and a 5% revision rate was observed. CONCLUSION: Processed nerve allografts performed well and were found to be safe and effective in sensory, mixed and motor nerve defects between 5 and 50 mm. The outcomes for safety and meaningful recovery observed in this study compare favorably to those reported in the literature for nerve autograft and are higher than those reported for nerve conduits.

Aggressively recurrent infantile myofibroma of the axilla and shoulder girdle.

Infantile myofibroma is the most common fibrous tumor of infancy, typically affecting neonates and children under 2 years of age. Though the multicentric variant portends a grave prognosis, solitary lesions have an excellent prognosis and frequently undergo spontaneous regression. Surgical excision of solitary lesions is usually curative. In this report, we describe a pediatric patient with an unusually aggressive solitary myofibroma of the axilla who ultimately required a forequarter amputation as a lifesaving measure following multiple tumor recurrences and progressive tumor growth. The clinical course, radiographic findings, histology, and management rationale are presented.

Multiple costimulatory blockade in the peripheral nerve allograft.

BACKGROUND: In the nerve allograft model, costimulation blockade has permitted good regeneration but is still inferior to the nerve isograft. We hypothesize that a short course of multiple costimulatory pathway blockade will be more effective in inhibiting the redundancy of the immune response and improve nerve regeneration through the nerve allograft. METHODS: The murine sciatic nerve allograft model was used to reconstruct a 1 cm sciatic nerve gap. Treatment consisted of the inhibition of the CD40, CD28/B7 and ICOS pathways and was compared with only single or double costimulation blockade. Assessment methods included quantitative histomorphometry and ELISPOT assay to quantify the host immune response after 3 weeks post-operatively. RESULTS: Triple costimulation blockade permitted regeneration through the nerve allograft that was equivalent to the nerve isograft. A short course of three doses was more effective than a single dose for all combinations tested. ELISPOT assay demonstrated minimal in vitro immune response with a short course of double or triple pathway-blocking agents. CONCLUSION: Costimulation blockade, especially with the simultaneous inhibition of multiple pathways, remains a promising strategy to promote regeneration through the peripheral nerve allograft, and may be uniquely suited to the temporary immunosuppressive requirements of the peripheral nerve allograft.

Salvage of a thumb replant using a bilobed dorsal metacarpal artery island flap: case report and literature review.

Amputations and degloving injuries of the hand are highly disabling, especially when they affect the thumb. Dorsal metacarpal artery (DMCA)-based flaps have been well-documented in the literature for use in extensive degloving injuries of both dorsal and palmar aspects of the thumb surface. Modifications on these flaps, such as the bilobed island flap, offer additional advantages when larger surface areas or more distal defects of the thumb are present. We present a review of the literature on the DMCA flap and describe its use to salvage a partial survival of a thumb amputation through the metacarpophalangeal joint.

The mental health system in Brazil: Policies and future challenges.

BACKGROUND: The aim of this paper is to assess the mental health system in Brazil in relation to the human resources and the services available to the population. METHODS: The World Health Organization Assessment Instrument for Mental Health Systems (WHO AIMS) was recently applied in Brazil. This paper will analyse data on the following sections of the WHO-AIMS: a) mental health services; and b) human resources. In addition, two more national datasets will be used to complete the information provided by the WHO questionnaire: a) the Executive Bureau of the Department of Health (Datasus); and b) the National Register of Health Institutions (CNS). RESULTS: There are 6003 psychiatrists, 18,763 psychologists, 1985 social workers, 3119 nurses and 3589 occupational therapists working for the Unified Health System (SUS). At primary care level, there are 104,789 doctors, 184, 437 nurses and nurse technicians and 210,887 health agents.The number of psychiatrists is roughly 5 per 100,000 inhabitants in the Southeast region, and the Northeast region has less than 1 psychiatrist per 100,000 inhabitants. The number of psychiatric nurses is insufficient in all geographical areas, and psychologists outnumber other mental health professionals in all regions of the country. The rate of beds in psychiatric hospitals in the country is 27.17 beds per 100,000 inhabitants. The rate of patients in psychiatric hospitals is 119 per 100,000 inhabitants. The average length of stay in mental hospitals is 65.29 days. In June 2006, there were 848 Community Psychosocial Centers (CAPS) registered in Brazil, a ratio of 0.9 CAPS per 200,000 inhabitants, unequally distributed in the different geographical areas: the Northeast and the North regions having lower figures than the South and Southeast regions. CONCLUSION: The country has opted for innovative services and programs, such as the expansion of Psychosocial Community Centers and the Return Home program to deinstitutionalize long-stay patients. However, services are unequally distributed across the regions of the country, and the growth of the elderly population, combined with an existing treatment gap is increasing the burden on mental health care. This gap may get even wider if funding does not increase and mental health services are not expanded in the country. There is not yet a good degree of integration between primary care and the mental health teams working at CAPS level, and it is necessary to train professionals to act as mental health planners and as managers. Research on service organization, policy and mental health systems evaluation are strongly recommended in the country. There are no firm data to show the impact of such policies in terms of community service cost-effectiveness and no tangible indicators to assess the results of these policies.

Median nerve mistaken for palmaris longus tendon: restoration of function with sensory nerve transfers.

Intraoperative iatrogenic nerve injuries occur despite vigilance in the operating room. Most of these injuries occur as a result of patient positioning, traction or pressure injury, hematoma, or technical error. The median nerve is especially susceptible to injury during carpal tunnel release. A rare but devastating injury of the median nerve is complete transection. The number of devastating injuries is not well known, as few of the injuries are documented or publicized. We report a case where the median nerve was harvested instead of the palmaris longus tendon. We present a review of the literature and suggest an alternative treatment to median nerve grafting using sensory nerve transfers in the hand.

Climbing the reconstructive ladder in the head and neck.

This article will give the reader an overview of the techniques used to reconstruct surgical, traumatic or congenital defects of the head and neck. The reconstructive ladder concept is used to provide a framework for understanding these techniques, from the simplest to the most complex, with the highest priority given to selecting the procedure that will provide restoration of form and function with the least risk.

Bridging the neural gap.

A major limitation to overall success in peripheral nerve surgery is time for regeneration. Although one can help speed up the regenerative process to some extent, success is hindered by issues such as number of coaptation sites, supply of donor nerves, and the limitations of nerve substitutes. In the case of a large gap, a nerve graft is often used to fill in the deficit. Autogenous nerve grafts are in limited supply, with sural nerve grafts being the primary source. Alternatives to the standard treatment include vein grafts, synthetic nerve conduits, nerve transfers, and nerve transplantation. Schwann cell-lined nerve conduits and tissue-engineered substitutions are still in their infancy and have some limited clinical application.

Palmar arch revascularization for arterial occlusion of the distal upper extremity.

During a period of nine years, 10 patients, ages 42 to 66 years (55 +/- 7, mean +/- SD) underwent upper extremity bypass for ischemic changes to the hand not responsive to conservative management. Patients were referred from the vascular department at the authors' institution. Preoperative angiograms were performed and attempts at angioplasty or intravenous attempts to dissolve clots were carried out (with tissue plasminogen activator-tPA) when appropriate. Patients with persistent upper extremity ischemia and an obvious occlusion with reconstitution in the hand were candidates for upper extremity bypass to the palmar arch. All patients had upper extremity bypasses performed with reverse saphenous vein grafts. The proximal anastomoses (end-to-side) were performed by either the vascular or plastic surgery team, while all distal anastomoses (end-to-side) were performed by plastic surgery team microscopic magnification to the deep or superficial palmar arch. Postoperative follow-up ranged from 3 months to 3 years. The bypass graft to the hand resulted in improved pain and resolution of tissue ischemia in all cases. Patients with preoperative ulcers were completely healed by 3 months. The results are in accordance with previous studies demonstrating that improved blood flow afforded by the procedure can improve the healing of recalcitrant ulcers and mitigate the symptoms of ischemic changes. In addition, end-to-side anastomosis to the palmar arch offers significant advantages, in that the continuity of the arch is maintained with all possible outflow vessels, and the problems associated with size discrepancy in the anastomosed vessels are eliminated.

Pulsed magnetic fields applied to a transferred arterial loop support the rat groin composite flap.

Pulsed magnetic fields have been shown to stimulate neovascularization in the authors' laboratory. The rat groin composite flap was used to create a prospective randomized trial to test the effectiveness of these pulsed magnetic fields. The skin paddle to this flap is highly consistent, and the authors proposed using the flap to study how pulsed magnetic fields affect composite flap survival when the dominant vessel to the flap is divided and flap survival becomes dependent on a transferred vessel loop. Forty-three rats had the tail artery microsurgically anastomosed to the femoral artery and placed between the groin musculature and the abdominal skin. Pulsed magnetic energy of 1 gauss was applied for 8 (n = 14) or 12 (n = 8) weeks to the experimental groups. Control groups were treated in a comparable manner for 8 (n = 16) or 12 (n = 5) weeks. After the 8 or 12 weeks, all groups had an 8 x 4-cm skin flap raised, and the superficial epigastric artery, the main feeding vessel, was ligated. After 5 days, the total area of the flap and the area of necrosis were traced onto velum paper for each rat. The percent survival was calculated per rat, and a mean survival percentage was calculated per group. The experimental animals treated with pulsed magnetic fields for 8 weeks had statistically significant improved flap survival over the control animals. The study provides evidence that pulsed magnetic energy stimulates angiogenesis and suggests a possible use of this modality to create island vascular flaps in otherwise random vascular territories.