Scott J. Farber

Limited regeneration in long acellular nerve allografts is associated with increased Schwann cell senescence

Repair of large nerve defects with acellular nerve allografts (ANAs) is an appealing alternative to autografting and allotransplantation. ANAs have been shown to be similar to autografts in supporting axonal regeneration across short gaps, but fail in larger defects due to a poorly-understood mechanism. ANAs depend on proliferating Schwann cells (SCs) from host tissue to support axonal regeneration. Populating longer ANAs places a greater proliferative demand on host SCs that may stress host SCs, resulting in senescence. In this study, we investigated axonal regeneration across increasing isograft and ANA lengths. We also evaluated the presence of senescent SCs within both graft types. A sciatic nerve graft model in rats was used to evaluate regeneration across increasing isograft (~autograft) and ANA lengths (20, 40, and 60 mm). Axonal regeneration and functional recovery decreased with increased graft length and the performance of the isograft was superior to ANAs at all lengths. Transgenic Thy1-GFP rats and qRT-PCR demonstrated that failure of the regenerating axonal front in ANAs was associated with increased levels of senescence related markers in the graft (senescence associated β-galactosidase, p16(INK4A), and IL6). Lastly, electron microscopy (EM) was used to qualitatively assess senescence-associated changes in chromatin of SCs in each graft type. EM demonstrated an increase in the presence of SCs with abnormal chromatin in isografts and ANAs of increasing graft length. These results are the first to suggest that SC senescence plays a role in limited axonal regeneration across nerve grafts of increasing gap lengths.

Peripheral nerve injury after local anesthetic injection.

BACKGROUND:A well-known complication of peripheral nerve block is peripheral nerve injury, whether from the needle or toxicity of the medication used. In this study, we sought to determine the extent of damage that results from intrafascicular injection of various commonly used local anesthetics (LAs). METHODS:Sixteen Lewis rats received an intrafascicular injection of saline (control) or 1 of 3 LAs (bupivacaine, lidocaine, or ropivacaine) into the sciatic nerve (n = 4). At a 2-week end point, the sciatic nerves were harvested for histomorphometric and electron microscopic analysis. RESULTS:Animals that received intrafascicular LA injections showed increased severity of injury as compared with control. In particular, there was a significant loss of large-diameter fibers as indicated by decreased counts (P < 0.01 for all LAs) and area (P < 0.01 for all LAs) of remaining fibers in severely injured versus noninjured areas of the nerve. There was a layering of severity of injury with most severely injured areas closest to and noninjured areas furthest from the injection site. Bupivacaine caused more damage to large fibers than the other 2 LAs. In all groups, fascicular transection injury from the needle was observed. Electron microscopy confirmed nerve injury. CONCLUSIONS:Frequently used LAs at traditional concentrations are toxic to and can injure the peripheral nerve. Any combination of motor and/or sensory sequelae may result due to the varying fascicular topography of a nerve.

“Supercharge Nerve Transfer to Enhance Motor Recovery, a Laboratory Study”

PURPOSE To investigate the ability of a supercharge end-to-side (SETS) nerve transfer to augment the effect of regenerating native axons in an incomplete rodent sciatic nerve injury model. METHODS Fifty-four Lewis rats were randomized to 3 groups. The first group was an incomplete recovery model (IRM) of the tibial nerve complemented with an SETS transfer from the peroneal nerve (SETS-IRM). The IRM consisted of tibial nerve transection and immediate repair using a 10-mm fresh tibial isograft to provide some, but incomplete, nerve recovery. The 2 control groups were IRM alone and SETS alone. Nerve histomorphometry, electron microscopy, retrograde labeling, and muscle force testing were performed. RESULTS Histomorphometry of the distal tibial nerve showed significantly increased myelinated axonal counts in the SETS-IRM group compared with the IRM and SETS groups at 5 and 8 weeks. Retrograde labeling at 8 weeks confirmed increased motoneuron counts in the SETS-IRM group. Functional recovery at 8 weeks showed a significant increase in muscle-specific force in the SETS-IRM group compared with the IRM group. CONCLUSIONS An SETS transfer enhanced recovery from an incomplete nerve injury as determined by histomorphometry, motoneuron labeling within the spinal cord, and muscle force measurements. CLINICAL RELEVANCE An SETS distal nerve transfer may be useful in nerve injuries with incomplete regeneration such as proximal Sunderland II- or III-degree injuries, in which long regeneration distance yields prolonged time to muscle reinnervation and suboptimal functional recovery.

Vascular malformation: Report of a case with eight-year follow up

An interesting example of a vascular malformation of the mandible has been presented. Early diagnosis made conservative treatment possible. Although the lesion was small, a considerable amount of hemorrhage was encountered during surgery. Adequate treatment was provided with ligation of external carotid arteries bilaterally in conjunction with curettage and packing. After an eight-year follow up, there has been no clinical or radiographic evidence of recurrence.

Nerve regeneration in rat limb allografts: evaluation of acute rejection rescue.

Background: Successful nerve regeneration is critical to the functional success of composite tissue allografts. The present study was designed to characterize the effect of acute rejection on nerve regeneration and functional recovery in the setting of orthotopic limb transplantation. Methods: A rat orthotopic limb transplantation model was used to evaluate the effects of acute rejection on nerve regeneration and motor recovery. Continuous administration of FK506 (full suppression), administration of FK506 for the first 8 of 12 weeks (late rejection), or delayed administration of FK506/dexamethasone following noticeable rejection (early rejection) was used to preclude or induce rejection following limb transplantation. Twelve weeks postoperatively, nerve regeneration was assessed by means of histomorphometric analysis of explanted sciatic nerve, and motor recovery was assessed by means of evoked muscle force measurement in extensor digitorum longus muscle. Results: A single episode of acute rejection that occurs immediately or late after reconstruction does not significantly alter the number of regenerating axonal fibers. Acute rejection occurring late after reconstruction adversely affects extensor digitorum longus muscle function in composite tissue allografts. Conclusions: Collected data reinforce that adequate immunosuppressant administration in cases of allogeneic limb transplantation ensures levels of nerve regeneration and motor functional recovery equivalent to that of syngeneic transplants. Prompt rescue following acute rejection was further demonstrated not to significantly affect nerve regeneration and functional recovery postoperatively. However, instances of acute rejection that occur late after reconstruction affect graft function. In total, the present study begins to characterize the effect of immunosuppression regimens on nerve regeneration and motor recovery in the setting of composite tissue allografts.

Anthropometric Outcome Measures in Patients With Metopic Craniosynostosis.

PURPOSE Treatment of metopic craniosynostosis is performed by either fronto-orbital advancement (FOA) or endoscopic-assisted techniques. Interfrontal angle (IFA) is a validated measure of trigonocephaly, but requires a computed tomography scan. The most common direct measure to assess surgical outcome in patients with trigonocephaly is frontal width (ft-ft). The aim of this study is to determine if frontal width correlates with IFA and successful surgical correction 1 year after treatment. A review of current morphologic assessment techniques is also provided. METHODS Three-dimensional computed tomography scans (preoperative and 1 year postoperative) of patients who underwent FOA (n = 13) or endoscopic (n = 13) treatment of metopic craniosynostosis were reviewed. Age-matched scans of unaffected patients served as controls. Frontal width was measured by a straight line between the bilateral frontotemporal points. Measurements were performed by 2 experienced observers and compared to IFA. RESULTS Mean frontal width at preoperative scan for endoscopic and open patients was 55 ± 0.6 and 64 ± 0.7 mm, respectively (Z-score 1.6 and -3.7). Mean frontal width at postoperative scan for endoscopic and open patients was 80 ± 0.4 and 81 ± 0.7 mm (Z-score 0.0 for both groups). Frontal width for endoscopic correction significantly correlated with IFA (r = 0.536, P = 0.005), as well as for the open patients (r = 0.704, P < 0.001). CONCLUSION Frontal width normalizes 1 year after operation, regardless of technique. Advantage of frontal width is that it can be measured in the clinic using a spreading vernier caliper. It correlates well with IFA and can be used as a metric for morphologic outcome.Purpose: Treatment of metopic craniosynostosis is performed by either fronto-orbital advancement (FOA) or endoscopic-assisted techniques. Interfrontal angle (IFA) is a validated measure of trigonocephaly, but requires a computed tomography scan. The most common direct measure to assess surgical outcome in patients with trigonocephaly is frontal width (ft–ft). The aim of this study is to determine if frontal width correlates with IFA and successful surgical correction 1 year after treatment. A review of current morphologic assessment techniques is also provided. Methods: Three-dimensional computed tomography scans (preoperative and 1 year postoperative) of patients who underwent FOA (n = 13) or endoscopic (n = 13) treatment of metopic craniosynostosis were reviewed. Age-matched scans of unaffected patients served as controls. Frontal width was measured by a straight line between the bilateral frontotemporal points. Measurements were performed by 2 experienced observers and compared to IFA. Results: Mean frontal width at preoperative scan for endoscopic and open patients was 55 ± 0.6 and 64 ± 0.7 mm, respectively (Z-score 1.6 and −3.7). Mean frontal width at postoperative scan for endoscopic and open patients was 80 ± 0.4 and 81 ± 0.7 mm (Z-score 0.0 for both groups). Frontal width for endoscopic correction significantly correlated with IFA (r = 0.536, P = 0.005), as well as for the open patients (r = 0.704, P < 0.001). Conclusion: Frontal width normalizes 1 year after operation, regardless of technique. Advantage of frontal width is that it can be measured in the clinic using a spreading vernier caliper. It correlates well with IFA and can be used as a metric for morphologic outcome.

Current Management of Zygomaticomaxillary Complex Fractures: A Multidisciplinary Survey and Literature Review.

Despite the prevalence of zygomaticomaxillary complex (ZMC) fractures, there is no consensus regarding the best approach to management. The aim of this study is to determine differences in ZMC fracture treatment among various surgical specialties. A survey was conducted regarding treatment of patients with different ZMC fractures that included a minimally displaced fracture (Case 1), a displaced fracture without diplopia (Case 2), a displaced fracture with diplopia (Case 3), and a complex comminuted fracture (Case 4). The survey was distributed to members of plastic surgery, oral maxillofacial surgery, and otolaryngology societies. The rates of surgical treatment, exploration of the orbital floor, and plating three or more buttresses were analyzed among the specialties. A total of 173 surgeons participated (46 plastic and reconstructive surgeons, 25 oral and maxillofacial surgeons, and 102 otolaryngologists). In Case 1, a significantly higher percentage of plastic surgeons recommend an operation (p < 0.01) compared with other specialties. More than 90% of surgeons would perform an operation on Case 2. Plastic surgeons explored the orbital floor (p < 0.01) and also fixated three or more buttresses more frequently (p < 0.01). More than 93% of surgeons would operate on Case 3, with plastic surgeons having the greatest proportion who fixed three or more buttresses (p < 0.01). In Case 4, there was no difference in treatment patterns between specialties. Across the specialties, more fixation was placed by surgeons with fewer years in practice (<10 years). Conclusion There is no consensus on standard treatment of ZMC fractures, as made evident by the survey. Significant variability in fracture type warrants an individualized approach to management. A thorough review on ZMC fracture management is provided.

Maxillomandibular Fixation by Plastic Surgeons: Cost Analysis and Utilization of Resources.

PurposeMaxillomandibular fixation (MMF) can be performed using various techniques. Two common approaches used are arch bars and bone screws. Arch bars are the gold standard and inexpensive, but often require increased procedure time. Bone screws with wire fixation is a popular alternative, but more expensive than arch bars. The differences in costs of care, complications, and operative times between these 2 techniques are analyzed. MethodsA chart review was conducted on patients treated over the last 12 years at our institution. Forty-four patients with CPT code 21453 (closed reduction of mandible fracture with interdental fixation) with an isolated mandible fracture were used in our data collection. The operating room (OR) costs, procedure duration, and complications for these patients were analyzed. ResultsOperative times were significantly shorter for patients treated with bone screws (P < 0.002). The costs for one trip to the OR for either method of fixation did not show any significant differences (P < 0.840). More patients with arch bar fixation (62%) required a second trip to the OR for removal in comparison to those with screw fixation (31%) (P < 0.068). This additional trip to the OR added significant cost. There were no differences in patient complications between these 2 fixation techniques. ConclusionsThe MMF with bone screws represents an attractive alternative to fixation with arch bars in appropriate scenarios. Screw fixation offers reduced costs, fewer trips to the OR, and decreased operative duration without a difference in complications. Cost savings were noted most significantly in a decreased need for secondary procedures in patients who were treated with MMF screws. Screw fixation offers potential for reducing the costs of care in treating patients with minimally displaced or favorable mandible fractures.

Vascularization is delayed in long nerve constructs compared with nerve grafts.

Introduction: Nerve regeneration across nerve constructs, such as acellular nerve allografts (ANAs), is inferior to nerve auto/isografts especially in the case of long defect lengths. Vascularization may contribute to poor regeneration. The time course of vascular perfusion within long grafts and constructs was tracked to determine vascularization. Methods: Male Lewis rat sciatic nerves were transected and repaired with 6 cm isografts or ANAs. At variable days following grafting, animals were perfused with Evans Blue albumin, and grafts were evaluated for vascular perfusion by a blinded observer. Results: Vascularization at mid‐graft was re‐established within 3–4 days in 6 cm isografts, while it was established after 10 days in 6 cm ANAs. Conclusions: Vascular perfusion is reestablished over a shorter time course in long isografts when compared with long ANAs. The differences in vascularization of long ANAs compared with auto/isografts suggest regenerative outcomes across ANAs could be affected by vascularization rates. Muscle Nerve 54: 319–321, 2016

An Alternative Method of Intermaxillary Fixation for Simple Pediatric Mandible Fractures.

PURPOSE Mandibular fractures represent a substantial portion of facial fractures in the pediatric population. Pediatric mandibles differ from their adult counterparts in the presence of mixed dentition. Avoidance of injury to developing tooth follicles is critical. Simple mandibular fractures can be treated with intermaxillary fixation (IMF) using arch bars or bone screws. This report describes an alternative to these methods using silk sutures and an algorithm to assist in treating simple mandibular fractures in the pediatric population. PATIENTS AND METHODS A retrospective chart review was performed and the records of 1 surgeon were examined. Pediatric patients who underwent treatment for a mandibular fracture in the operating room from 2011 to 2015 were identified using Common Procedural Terminology codes. Data collected included age, gender, type of fracture, type of treatment used, duration of fixation, and presence of complications. RESULTS Five patients with a mean age of 6.8 years at presentation were identified. Fracture types were unilateral fractures of the condylar neck (n = 3), bilateral fractures of the condylar head (n = 1), and a unilateral fracture of the condylar head with an associated parasymphyseal fracture (n = 1). IMF was performed in 4 patients using silk sutures, and bone screw fixation was performed in the other patient. No post-treatment complications or malocclusion were reported. Average duration of IMF was 18.5 days. CONCLUSIONS An algorithm is presented to assist in the treatment of pediatric mandibular fractures. Silk suture fixation is a viable and safe alternative to arch bars or bone screws for routine mandibular fractures.