targeted-muscle-reinnervation-surgical-protocol-for-randomized

Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain

Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the ...

regenerative-peripheral-nerve-interface-surgical-protocol-for

Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain

Surgical procedures, including nerve reconstruction and end-organ muscle reinnervation, have become more prominent in the prosthetic field over the past ...

University of Alberta

Many North American medical schools have removed didactic surgical teaching from the nonclinical years, and there has been a trend toward shortening surgical clerkships. Of concern is that this policy has led to a decrease in surgical exposure and a diminished interest in students pursuing a surgical career. We aimed to determine the effect of curricular change on practical experiences during surgical clerkship and to evaluate overall practical clinical exposure of students during surgical clerkship.

What procedures are students doing during undergraduate surgical clerkship?

While injured neurons regenerate their axons in the peripheral nervous system, it is well recognized that functional recovery is frequently poor. Animal experiments in which injured motoneurons remain without peripheral targets (chronic axotomy) and Schwann cells in distal nerve stumps remain without innervation (chronic denervation) revealed that it is the duration of chronic axotomy and Schwann cell denervation that accounts for this poor functional recovery and not irreversible muscle atrophy that has been so commonly thought to be the reason. More recently, we demonstrated that axon outgrowth across lesion sites is a major contributing factor to the long delays incurred between the injury and the reinnervation of denervated targets. In the rat, a period of 1 month transpires before all motoneurons regenerate their axons across a lesion site. We have developed a technique of 1 h low-frequency electrical stimulation (ES) of the proximal nerve stump just after surgical repair of a transected peripheral nerve that greatly accelerates axon outgrowth. This technique has been applied in patients after carpal tunnel release surgery where the ES promoted the regeneration of all median nerves to reinnervate thenar muscles within 6-8 months, which contrasted with failure of any injured nerves to reinnervate muscles in the same time frame without ES. These findings are very promising such that the ES method could become a clinically viable tool for accelerating axon regeneration and muscle reinnervation.

Chapter 24: Electrical stimulation for improving nerve regeneration: where do we stand?

Fibroproliferative disorders (FPDs) are common and serious disorders. Hypertrophic scar (HSc) and keloids represent the dermal equivalents of FPD and impose lower mortality but great morbidity. This article reviews current knowledge in the pathophysiology and molecular and cellular characteristics of postburn HSc. Additionally, current treatment modalities and future treatment options based on advancements in the understanding of the pathophysiology of HSc are discussed.

Pathophysiology and management of the burn scar.

Hypertrophic scar (HTS), a fibroproliferative disorder (FPD), complicates burn wound healing. Although the pathogenesis is not understood, prolonged inflammation is a known contributing factor. Emerging evidence suggests that fibroblasts regulate immune/inflammatory responses through toll-like receptor 4 (TLR4) activated by lipopolysaccharide (LPS) through adaptor molecules, leading to nuclear factor kappa-light-chain-enhancer of activated B cells and mitogen-activated protein kinases activation, cytokine gene transcription and co-stimulatory molecule expression resulting in inflammation. This study explored the possible role of TLR4 in HTS formation. Paired normal and HTS tissue from burn patients was collected and dermal fibroblasts isolated and cultured. Immunohistochemical analysis of tissues demonstrated increased TLR4 staining in HTS tissue. Quantitative RT-PCR of three pairs of fibroblasts demonstrated mRNA levels for TLR4 and its legend myeloid differentiation factor 88 (MyD88) in HTS fibroblasts were increased significantly compared with normal fibroblasts. Flow cytometry showed increased TLR4 expression in HTS fibroblasts compared with normal. ELISA demonstrated protein levels for prostaglandin E2, interleukin (IL)-6, IL-8 and monocyte chemotactic protein-1 (MCP-1) were significantly increased in HTS fibroblasts compared to normal. When paired normal and HTS fibroblasts were stimulated with LPS, significant increases in mRNA and protein levels for MyD88, IL-6, IL-8, and MCP-1 were detected. However, when transfected with MyD88 small interfering RNA (siRNA), then stimulated with LPS, a significant decrease in mRNA and protein levels for these molecules compared to only LPS-stimulated fibroblasts was detected. In comparison, a scramble siRNA transfection did not affect mRNA or protein levels for these molecules. Results demonstrate LPS stimulates proinflammatory cytokine expression in dermal fibroblasts and MyD88 siRNA eliminates the expression. Therefore, controlling inflammation and manipulating TLR signaling in skin cells may result in novel treatment strategies for HTS and other FPD.

Toll-like receptors expressed by dermal fibroblasts contribute to hypertrophic scarring.

Progressive atrophy of Schwann cells in denervated nerve stumps is a major reason for progressive failure of functional recovery after peripheral nerve injury and surgical repair.

Side-to-side nerve grafts sustain chronically denervated peripheral nerve pathways during axon regeneration and result in improved functional reinnervation.

Current surgical management of obstetrical brachial plexus injury is primary reconstruction with sural nerve grafts. Recently, the nerve-to-nerve transfer technique has been used to treat brachial plexus injury in adults, affording the benefit of distal coaptations that minimize regenerative distance. The purpose of this study was to test the hypothesis that nerve transfers are effective in reconstructing isolated upper trunk obstetrical brachial plexus injuries.

Distal nerve transfers are effective in treating patients with upper trunk obstetrical brachial plexus injuries: an early experience.

Functional recovery after peripheral nerve injury and surgical repair declines with time and distance because the injured neurons without target contacts (chronic axotomy) progressively lose their regenerative capacity and chronically denervated Schwann cells (SCs) atrophy and fail to support axon regeneration. Findings that brief low frequency electrical stimulation (ES) accelerates axon outgrowth and muscle reinnervation after immediate nerve surgery in rats and human patients suggest that ES might improve regeneration after delayed nerve repair. To test this hypothesis, common peroneal (CP) neurons were chronically axotomized and/or tibial (TIB) SCs and ankle extensor muscles were chronically denervated by transection and ligation in rats. The CP and TIB nerves were cross-sutured after three months and subjected to either sham or one hour 20Hz ES. Using retrograde tracing, we found that ES significantly increased the numbers of both motor and sensory neurons that regenerated their axons after a three month period of chronic CP axotomy and/or chronic TIB SC denervation. Muscle and motor unit forces recorded to determine the numbers of neurons that reinnervated gastrocnemius muscle demonstrated that ES significantly increased the numbers of motoneurons that reinnervated chronically denervated muscles. We conclude that electrical stimulation of chronically axotomized motor and sensory neurons is effective in accelerating axon outgrowth into chronically denervated nerve stumps and improving target reinnervation after delayed nerve repair. Possible mechanisms for the efficacy of ES in promoting axon regeneration and target reinnervation after delayed nerve repair include the upregulation of neurotrophic factors.

Brief electrical stimulation improves nerve regeneration after delayed repair in Sprague Dawley rats.

The University of Alberta established a resident-run hand clinic in 2005 to expeditiously manage the growing numbers of patients with traumatic hand injuries. The purpose of this study was to examine the clinical volume and types of cases assessed and treated in the clinic, as well as gauge patient satisfaction with care received.

The Utility and Efficiency of a Resident Hand Clinic for the Management of Acute Hand Trauma at the University of Alberta.

Neurofibromatosis type 2 (NF2) is a genetic disorder characterized by mutations of the NF2 tumor suppressor gene that predisposes patients to develop multiple tumors in the peripheral and central nervous system. The most common neoplasms associated with the disease are schwannomas and meningiomas. Both have been shown to contain abnormalities in chromosome 22 and the NF2 gene, suggesting a genetic component to their pathogenesis. Perineuriomas are rare benign tumors arising from the perineural cells. They are commonly classified as intraneural and soft tissue perineuriomas. Several studies have reported mutations in genes on chromosome 22 in both types of perineuriomas, and there are reports of soft tissue perineuriomas associated with NF2 gene mutations. Despite this, perineuriomas are not considered as part of the NF2 constellation of tumors.

Association of intraneural perineurioma with neurofibromatosis type 2.

Hepatic artery thrombosis represents a potentially fatal complication following liver transplantation. Rates of hepatic artery thrombosis are significantly higher in children, with mortality reported up to 80 percent. Microsurgical anastomosis has been shown to decrease the rate of hepatic artery thrombosis and now represents the standard of care at the authors' institution. In this article, the authors present the largest study of its type directly comparing rates of hepatic artery thrombosis with and without microsurgical reconstruction of the hepatic artery.

The Transition to Microsurgical Technique for Hepatic Artery Reconstruction in Pediatric Liver Transplantation.

The purpose of this study was to determine the effectiveness of using ultrasonic assisted liposuction (UAL) to achieve sufficient breast symmetry allowing for the use of same sized implants in patients presenting for elective breast augmentation surgery.

Breast Equalization Augmentation: The Use of Ultrasonic Assisted Liposuction for Correction of Primary Breast Asymmetry with Bilateral Augmentation.

Hepatic artery thrombosis (HAT) represents a devastating and often fatal complication of liver transplantation. Due to the small vessel caliber in pediatric patients, the use of an operating microscope has largely become the standard for hepatic artery reconstruction to reduce the rate of HAT. Recent evidence, however, suggests that loupe magnification for anastomosis may be equally effective. We aimed to determine the effect of magnification on the rate of hepatic artery thrombosis in pediatric liver transplantation.

Effect of magnification in pediatric liver transplantation: A systematic review and meta-analysis.

Severe traumatic scalp avulsion requiring an uncommon reconstruction: omental free tissue transfer flap.

Painful conditions such as residual limb pain (RLP) and phantom limb pain (PLP) can manifest after amputation. The mechanisms underlying such postamputation pains are diverse and should be addressed accordingly. Different surgical treatment methods have shown potential for alleviating RLP due to neuroma formation - commonly known as neuroma pain - and to a lesser degree PLP. Two reconstructive surgical interventions, namely targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI), are gaining popularity in postamputation pain treatment with promising results. However, these two methods have not been directly compared in a randomised controlled trial (RCT). Here, we present a study protocol for an international, double-blind, RCT to assess the effectiveness of TMR, RPNI, and a non-reconstructive procedure called neuroma transposition (active control) in alleviating RLP, neuroma pain, and PLP.

ArticleTotal : 2	Year
Publication title Cited by 5	2024
Publication title Cited by 5	2024

Article	Year
What procedures are students doing during undergraduate surgical clerkship? Canadian journal of surgery. Journal canadien de chirurgie\| PubMed ID: 17152570	2006
Chapter 24: Electrical stimulation for improving nerve regeneration: where do we stand? International review of neurobiology\| PubMed ID: 19682653	2009
Pathophysiology and management of the burn scar. Clinics in plastic surgery\| PubMed ID: 19793560	2009
Toll-like receptors expressed by dermal fibroblasts contribute to hypertrophic scarring. Journal of cellular physiology\| PubMed ID: 20945369	2011
Side-to-side nerve grafts sustain chronically denervated peripheral nerve pathways during axon regeneration and result in improved functional reinnervation. Neurosurgery\| PubMed ID: 21346654	2011
Distal nerve transfers are effective in treating patients with upper trunk obstetrical brachial plexus injuries: an early experience. Plastic and reconstructive surgery\| PubMed ID: 24281645	2013
Brief electrical stimulation improves nerve regeneration after delayed repair in Sprague Dawley rats. Experimental neurology\| PubMed ID: 25842267	2015
The Utility and Efficiency of a Resident Hand Clinic for the Management of Acute Hand Trauma at the University of Alberta. Plastic surgery (Oakville, Ont.)\| PubMed ID: 31106180	2019
Association of intraneural perineurioma with neurofibromatosis type 2. Acta neurochirurgica\| PubMed ID: 32529330	2020
The Transition to Microsurgical Technique for Hepatic Artery Reconstruction in Pediatric Liver Transplantation. Plastic and reconstructive surgery\| PubMed ID: 34181598	2021
Breast Equalization Augmentation: The Use of Ultrasonic Assisted Liposuction for Correction of Primary Breast Asymmetry with Bilateral Augmentation. Aesthetic plastic surgery\| PubMed ID: 34462800	2022
Effect of magnification in pediatric liver transplantation: A systematic review and meta-analysis. Pediatric transplantation\| PubMed ID: 35001466	2022
Severe traumatic scalp avulsion requiring an uncommon reconstruction: omental free tissue transfer flap. Trauma surgery & acute care open\| PubMed ID: 35340704	2022
Surgical treatments for postamputation pain: study protocol for an international, double-blind, randomised controlled trial. Trials\| PubMed ID: 37131180	2023
Correction: Surgical treatments for postamputation pain: study protocol for an international, double-blind, randomised controlled trial. Trials\| PubMed ID: 37814331	2023

Adil Ladak

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