Gal - T Knockout Porcine Nerve Xenografts Support Axonal Regeneration in a Rodent Sciatic Nerve Model.

BACKGROUND: Nerve xenografts harvested from transgenic α1,3-galactosyltransferase knockout (GalT-KO) pigs lack the epitope responsible for hyperacute rejection in pig-to-primate transplants. It is unknown whether these cold preserved nerve grafts support axonal regeneration in another species during and after immunosuppression. In this study, we compare outcomes between autografts and cold preserved xenografts in a rat sciatic model of nerve gap repair. METHODS: Fifty male Lewis rats had a 1 cm sciatic nerve defect repaired using either: autograft and suture (n=10); 1-week or 4-week cold preserved xenograft and suture (n=10 per group); 1-week or 4-week cold preserved xenograft and photochemical tissue bonding using a human amnion wrap (PTB/HAM) (n=10 per group). Rats with xenografts were given tacrolimus until 4 months post-operatively. At 4 and 7 months, rats were euthanized and nerve sections harvested. Monthly sciatic functional index (SFI) scores were calculated. RESULTS: All groups showed increases in SFI scores by 4 and 7 months. The autograft suture group had the highest axon density at 4 and 7 months. The largest decrease in axon density from 4 to 7 months was in the 1-week cold preserved PTB/HAM group. The only significant difference between group SFI scores occurred at 5 months, when both 1-week cold preserved groups had significantly lower scores than the 4-week cold preserved suture group. CONCLUSIONS: Our results in the rat sciatic model suggest that GalT-KO nerve xenografts may be viable alternatives to autografts and demonstrate the need for further studies of long-gap repair and comparison with acellular nerve allografts. CLINICAL RELEVANCE: This proof-of-concept study in the rat sciatic model demonstrates that cold preserved GalT-KO porcine xenografts support axonal regeneration, as well as axonal viability following immunosuppression withdrawal. These results further suggest a role for both cold preservation and photochemical tissue bonding in modulating the immunological response at the nerve repair site.

A Technical Guide for Sciatic Nerve Targeted Muscle Reinnervation in a Transfemoral Amputee.

There are approximately 2 million people living with the loss of a major limb in America. It is estimated that 95% of these will have some form of pain associated with their amputation. Phantom limb pain, related to symptomatic neuromas, contributes to amputation morbidity and can be difficult to treat. Studies have shown that targeted muscle reinnervation (TMR), by giving symptomatic neuromas "somewhere to go and something to do," can be an effective therapy. However, a large proportion of surgeons still treat symptomatic neuromas by burying them in nearby tissue. Methods: We treated a patient with previous above-the-knee amputation, complicated by a symptomatic neuroma, with TMR. We identified and described nine steps to the procedure. Our description is accompanied by illustrative, intraoperative photographs and technical pearls. Results: This article provides a description of TMR technique involving a neuroma of the sciatic nerve and its branches, to treat an above-the-knee amputation, with the aim of making this approach more accessible. At 9-month follow-up, the patient had active firing of the recipient muscles with donor nerve stimulation indicating successful reinnervation. The patient continued to report stump pain, but with intermittent pain-free days. Conclusions: TMR has proven potential as a therapy for amputation-related, neuropathic pain. With this technical guide to TMR, surgeons should feel more comfortable adding this technique to their armamentarium, to be utilized either at the time of amputation or as a secondary measure.

The Relationship of Psychiatric Comorbidities and Their Impact on Trigger Site Deactivation Surgery for Headaches.

BACKGROUND: Patients seeking trigger site deactivation surgery for headaches often have debilitating symptoms that can affect their functional and mental health. Although prior studies have shown a strong correlation between psychiatric variables and chronic headaches, their associations in patients undergoing surgery have not been fully elucidated. This study aims to analyze psychiatric comorbidities and their impact on patients undergoing trigger site deactivation surgery for headaches. METHODS: One hundred forty-two patients were prospectively enrolled. Patients were asked to complete the Patient Health Questionnaire-2 and Migraine Headache Index surveys preoperatively and at 12 months postoperatively. Data on psychiatric comorbidities were collected by means of both survey and retrospective chart review. RESULTS: Preoperatively, 38 percent of patients self-reported a diagnosis of depression, and 45 percent of patients met Patient Health Questionnaire-2 criteria for likely major depressive disorder (Patient Health Questionnaire-2 score of ≥3). Twenty-seven percent of patients reported a diagnosis of generalized anxiety disorder. Patients with depression and anxiety reported more severe headache symptoms at baseline. At 1 year postoperatively, patients with these conditions had successful surgical outcomes comparable to those of patients without these conditions. Patients also reported a significant decrease in their Patient Health Questionnaire-2 score, with 22 percent of patients meeting criteria suggestive of depression, compared to 45 percent preoperatively. CONCLUSIONS: There is a high prevalence of depression and anxiety in patients undergoing trigger site deactivation surgery. Patients with these comorbid conditions achieve successful surgical outcomes comparable to those of the general surgical headache population. Furthermore, trigger site deactivation surgery is associated with a significant decrease in depressive symptoms.

The Efficacy of Surgical Treatment for Headaches in Patients with Prior Head or Neck Trauma.

BACKGROUND: Patients undergoing trigger-site deactivation surgery for headaches report a high prevalence (approximately 37 percent) of prior head or neck injury. Traditional medical treatment often fails to treat these posttraumatic patients. It is unclear whether surgery mirrors these poor outcomes. This study aims to describe the characteristics of posttraumatic headache surgery patients and compare their postoperative results to those of patients without a history of head or neck injury. METHODS: One hundred forty-two patients undergoing trigger-site deactivation surgery were prospectively enrolled. Patients were requested to complete a preoperative questionnaire on headache history, including the Migraine Headache Index and information on prior head or neck injury. Follow-up surveys were requested at approximately 12 months postoperatively. RESULTS: Seventy patients (49 percent) reported a history of head or neck injury, and 41 (29 percent) classified the injury as the precipitating event leading to their headache onset. Patients with a precipitating event were significantly less likely to report a family history of migraine. There was no significant difference in mean preoperative Migraine Headache Index between cohorts. At 12 months postoperatively, there was no significant difference in Migraine Headache Index reduction between groups. The proportion of patients who experienced at least a 50 and 80 percent improvement in Migraine Headache Index per group, respectively, was 83 and 67 percent (atraumatic), 76 and 68 percent (posttraumatic), and 71 and 63 percent (precipitating event). CONCLUSIONS: This study suggests that surgical outcomes in posttraumatic headache patients are comparable to those without injury. Trigger-site deactivation surgery candidates with a history of injury can therefore expect similar outcomes as reported for patients overall. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Photochemical Tissue Passivation Prevents Contracture of Full Thickness Wounds in Mice.

BACKGROUND AND OBJECTIVES: Wound contracture formation from excessive myofibroblast activity can result in debilitating morbidities. There are currently no treatments to prevent contracture. Photochemical tissue passivation (PTP), an established, safe, and user-friendly treatment modality, crosslinks collagen by a light-activated process, thus modulating the wound healing response and scarring. We hypothesised that PTP treatment would reinforce wounds by blunting the fibrotic response thus limiting contracture. STUDY DESIGN/MATERIALS AND METHODS: Full-thickness, 1 cm × 1 cm excisional wounds were created on the dorsum of 32 C57BL/6 mice. Treated wounds were painted with photosensitizing dye and exposed to visible light. Wounds were serially photographed over 6 weeks to measure wound contracture. At 7, 14, 21, and 42 days after wound creation, mice were euthanized and wounds were harvested for histologic review by a dermatopathologist. RESULTS: By Day 7, control wounds had significantly more contracture than those treated with PTP (33.0 ± 17.1% and 19.3 ± 9.0%, respectively; P = 0.011). PTP-treated wounds maintained approximately 20% less contracture than controls from Day 14 and on (P < 0.05). By Day 42, wounds had contracted by 86.9 ± 5.5% in controls and 64.2 ± 3.2% in PTP-treated wounds (P < 0.03). Histologically, PTP wounds had earlier growth and development of dermal collagen, neovascularization, and development of skin appendages, compared with control wounds. CONCLUSIONS: PTP significantly limits contracture of full-thickness wounds and improves wound healing. PTP-treated wounds histologically demonstrate more mature structural organization than untreated wounds and closely resemble native skin. PTP treatment may be applicable not only for excisional wounds, but also for wounds with a high incidence of contracture and associated morbidity. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.