Subhro K. Sen

Current approach to radial nerve paralysis.

LEARNING OBJECTIVES After studying this article, the participant should be able to: 1. Identify all potential points of radial nerve compression and other likely causes of radial nerve injury. 2. Accurately diagnose both surgical and nonsurgical causes of radial nerve paralysis. 3. Define a safe and effective approach to the surgical release and reconstruction of the radial nerve. Radial nerve paralysis, which can result from a complex humerus fracture, direct nerve trauma, compressive neuropathies, neuritis, or (rarely) from malignant tumor formation, has been reported throughout the literature, with some controversy regarding its diagnosis and management. The appropriate management of any radial nerve palsy depends primarily on an accurate determination of its cause, severity, duration, and level of involvement. The radial nerve can be injured as proximally as the brachial plexus or as distally as the posterior interosseous or radial sensory nerve. This article reviews the etiology, prognosis, and various treatments available for radial nerve paralysis. It also provides a new classification system and treatment algorithm to assist in the management of patients with radial nerve palsies, and it offers a simple, five-step approach to radial nerve release in the forearm.

Dose-dependent effects of FK506 on neuroregeneration in a rat model.

This study explored the effects of different doses of FK506 on peripheral nerve regeneration, to determine whether neuroregeneration could be enhanced without the toxicity of systemic immunosuppression. In the first part of the study, subimmunosuppressive doses of FK506 were determined by examining skin allograft survival in a rat model. Full-thickness skin grafts (2 cm2) from Wistar rats were grafted to recipient Lewis rats. The procedure was performed for six groups (n = 6). The control group received no FK506, and the other five groups received daily doses of FK506 of 0.125, 0.25, 0.5, 1.0, or 2.0 mg/kg. Animals that received 2.0 mg/kg FK506 per day exhibited complete skin graft take, whereas all other groups demonstrated complete rejection. After determination of the immunosuppressive dose of FK506, the neuroregenerative effects of different doses of FK506 were explored by assessing nerve regeneration in 80 rats after tibial nerve transection and repair. The control group received no FK506, whereas the other four groups were given daily doses of FK506 of 0.25, 0.5, 1.0, or 2.0 mg/kg. Rats were euthanized at three time points (25, 30, and 35 days), to fully investigate the effects of different FK506 dosing regimens on neuroregeneration. Histomorphometric analyses performed on postoperative days 30 and 35 demonstrated statistically significant improvements in neuroregeneration with subimmunosuppressive FK506 doses of 0.5 and 1.0 mg/kg per day. Therefore, the study demonstrated that neuroregeneration was enhanced at low doses of FK506 that were not sufficient to prevent skin allograft rejection.

The effects of rapamycin in murine peripheral nerve isografts and allografts.

The FKBP-12-binding ligand FK506 has been successfully used to stimulate nerve regeneration and prevent the rejection of peripheral nerve allografts. The immunosuppressant rapamycin, another FKBP-12-binding ligand, stimulates axonal regeneration in vitro, but its influence on nerve regeneration in peripheral nerve isografts or allografts has not been studied. Sixty female inbred BALB/cJ mice were randomized into six tibial nerve transplant groups, including three isograft and three allograft (C57BL/6J) groups. Grafts were left untreated (groups I and II), treated with FK506 (groups III and IV), or treated with rapamycin (groups V and VI). Nerve regeneration was quantified in terms of histomorphometry and functional recovery, and immunosuppression was confirmed with mixed lymphocyte reactivity assays. Animals treated with FK506 and rapamycin were immunosuppressed and demonstrated significantly less immune cell proliferation relative to untreated recipient animals. Although every animal demonstrated some functional recovery during the study, animals receiving an untreated peripheral nerve allograft were slowest to recover. Isografts treated with FK506 but not rapamycin demonstrated significantly increased nerve regeneration. Nerve allografts in animals treated with FK506, and to a lesser extent rapamycin, however, both demonstrated significantly more nerve regeneration and increased nerve fiber widths relative to untreated controls. The authors suggest that rapamycin can facilitate regeneration through peripheral nerve allografts, but it is not a neuroregenerative agent in this in vivo model. Nerve regeneration in FK506-treated peripheral nerve isografts and allografts was superior to that found in rapamycin-treated animals. Rapamycin may have a role in the treatment of peripheral nerve allografts when used in combination with other medications, or in the setting of renal failure that often precludes the use of calcineurin inhibitors such as FK506.

Assessment of the immune response to dose of nerve allografts.

Nerve allotransplantation provides a limitless source of nerve graft material for the reconstruction of large neural defects. It does require systemic immunosuppression or induction of immune unresponsiveness to prevent allograft rejection. It is unknown whether a greater volume of nerve graft material will increase the risk of rejection or the need for more intensive immunosuppression. This study assessed the relationship between the quantity of nerve tissue transplanted and the magnitude of the resulting immune response. Forty female (BALB/c) mice were randomly assigned to two groups that received either nerve isografts (BALB/c) or nerve allografts (C57BL/6). Each group was then subdivided into two groups that received either one or 10 sciatic nerve graft inlays. Histological and immunological assessments were performed at 10 days after engraftment. Histologic analysis demonstrated greater cellular infiltration in the allograft than the isograft groups but no appreciable difference in infiltration related to quantity of transplanted nerve tissue. In vitro assessments of the immune response using mixed lymphocyte assays and limiting dilution analysis similarly demonstrated a robust immune response to allografts but no effect on quantity of transplanted nerve tissue. These data suggest that larger peripheral nerve allografts may not be subject to increased risk for rejection.

Fascia-only anterolateral thigh flap for extremity reconstruction.

IntroductionThe ability to use the anterolateral thigh (ALT) flap as a vascularized fascial flap, without skin or muscle, was first documented by Koshima et al in 1989. The authors mention the possibility of using the fascia alone for dural reconstruction. Despite its description more than 20 years ago, little literature exists on the application of the ALT flap as a vascularized fascial flap. In our experience, the ALT flap can be used as a fascia-only flap for thin, pliable coverage in extremity reconstruction. MethodsAfter approval from the institutional review board, the medical records and photographs of patients who had undergone fascia-only ALT free flaps for extremity reconstruction were reviewed. Photographic images of patients were then matched to patients who had undergone either a muscle-only or a fasciocutaneous free flap reconstruction of an extremity. Photographs of the final reconstruction were then given to medical and nonmedical personnel for analysis, focusing on aesthetics including color and contour. ResultsReview of cases performed over a 2-year period demonstrated similar ease of harvest for fascia-only ALT flaps compared to standard fasciocutaneous ALT flaps. Fascia-only flaps were used for thin, pliable coverage in the upper and lower extremities. There was no need for secondary procedures for debulking or aesthetic flap revision. In contrast to muscle flaps, which require muscle atrophy over time to achieve their final appearance, there was a similar flap contour from approximately 1 month postoperatively throughout the duration of follow-up. When a large flap is required, the fascia-only ALT has the advantage of a single-line donor-site scar. Photograph comparison to muscle flaps with skin grafts and fasciocutaneous flaps demonstrated improved color, contour, and overall aesthetic appearance of the fascia-only ALT over muscle and fasciocutaneous flaps. ConclusionsThe fascia-only ALT flap provides reliable, thin, and pliable coverage with improved contour and color over muscle and fasciocutaneous flaps. The fascia-only ALT is another excellent option for reconstructive surgery of the extremities.

Changing attitudes toward hand allotransplantation among North American hand surgeons.

ObjectivesAlthough more than 70 hand transplants have been performed worldwide, the appropriate clinical indications for this operation are still being determined. Cost and patient exposure to the challenges of lifelong immunosuppression for what is a quality of life-improving (but not life-saving) operation are the focus of the ongoing discussion. A study performed in 2007 showed that surgeons’ opinions on the issue varied widely. Recently, more information has been made available regarding long-term patient outcomes, and significant improvements in immunotherapy protocols have been reported. In light of this, we sought to examine changing attitudes regarding hand allotransplantation and its indications by surveying hand surgeons. MethodsAn email-based survey was sent to members of the American Society for Surgery of the Hand. Demographic information and practice profiles were identified, followed by their risk assessment of hand allotransplants and endorsement of performing the operation in different clinical scenarios. Additional questions focused on the appropriate indications for hand allotransplantation, as well as the procedure’s associated ethical and financial implications. ResultsA total of 385 surgeons responded to the survey (14% response rate). The majority (82%) considered hand transplantation to be a high-risk operation (as opposed to 27% in hand replantation), with 78% citing lifelong immunosuppression as the primary factor impacting their overall risk assessment. The most commonly accepted indication for hand vascularized composite allotransplantation was loss of bilateral hands (80% in favor). Dominant hand loss (with an intact contralateral hand) was a far less frequently accepted indication (36% in favor). Patient adherence to immunosuppressive regimens (51%) and expectations of functional/aesthetic outcome (38%) were the most frequently chosen top psychosocial issues that must be addressed by the surgical/medical teams involved in the operation. ConclusionsOur study’s results demonstrate increasing overall support for hand allotransplantation and increasing acceptance of today’s immunosuppressive regimens compared to prior literature. Bilateral hand loss remains the primary agreed-upon indication for transplantation. Despite increasing acceptance in the surgical community, the dangers of chronic immunosuppression, cost and patient adherence continue to be the primary concerns hindering its broader acceptance.

Injuries to appendage extremities and digit tips: A clinical and cellular update

Background The regrowth of amputated appendage extremities and the distal tips of digits represent models of tissue regeneration in multiple vertebrate taxa. In humans, digit tip injuries, including traumatic amputation and crush injuries, are among the most common type of injury to the human hand. Despite clinical reports demonstrating natural regeneration of appendages in lower vertebrates and human digits, current treatment options are suboptimal, and are complicated by the anatomical complexities and functions of the different tissues within the digits. Results: In light of these challenges, we focus on recent advancements in understanding appendage regeneration from model organisms. We pay special attention to the cellular programs underlying appendage regeneration, where cumulative data from salamanders, fish, frogs, and mice indicate that regeneration occurs by the actions of lineage‐restricted precursors. We focus on pathologic states and the interdependency that exists, in both humans and animal models, between the nail organ and the peripheral nerves for successful regeneration. Conclusions: The increased understanding of regeneration in animal models may open new opportunities for basic and translational research aimed at understanding the mechanisms that support limb regeneration, as well as amelioration of limb abnormalities and pathologies. Developmental Dynamics 244:641–650, 2015.

Comparing Muscle and Fasciocutaneous Free Flaps in Lower Extremity Reconstruction--Does It Matter?

IntroductionPlastic surgeons are often asked to assist with the reconstruction of lower extremity wounds. These patients many times require free tissue transfer for coverage given paucity of soft tissue. Anecdotally, many orthopedic surgeons prefer muscle coverage—particularly in the setting of potentially infected bone. Todays surgeons now easily harvest and transfer fasciocutaneous flaps—a versatile option with less donor-site morbidity. We hypothesized that there would be no difference in outcomes between these 2 types of reconstruction. MethodsWe performed a single-institution retrospective review of lower extremity free flap reconstructions in the last 10 years. Demographics, preoperative and postoperative course, and the documented time to weight-bearing and bony union were collected. Major cohorts compared were muscle free flaps and fasciocutaneous free flaps, further divided into subgroups including acute trauma, tumor resection, osteomyelitis, and nonunion. Data comparisons were made using paired t test and Fischer exact tests. ResultsThere were 121 patients who met inclusion criteria—86 in the muscle flap group, and 35 in the fasciocutaneous group and demographics were equal. Total complication rates were higher in smokers than nonsmokers (P < 0.03). There was no significant difference in major or minor complication rates between muscle and fasciocutaneous flaps in any subgroup. In both the acute fracture group and the infected nonunion group, there was a significantly faster return to weight bearing in the fasciocutaneous group (P < 0.03) although there was no difference in documented time to bony union. Patients who underwent fasciocutaneous reconstruction were more likely to require revisionary surgery for improved aesthetics (P < 0.001). ConclusionsOur data suggest that in essentially all clinical parameters, there is no difference between free flap type used for soft tissue coverage of the lower extremity. Patients undergoing reconstruction with a fasciocutaneous flap may return to weight bearing earlier—although they are more likely to require elective flap revisions. These results imply essentially equivalent outcomes regardless of flap type or operative indication, in contrast with some of the biases in the orthopedic community. The particular flap chosen for any reconstruction should remain solely at the discretion of the plastic surgeon.

Cover Image: INJURIES TO APPENDAGE EXTREMITIES AND DIGIT TIPS

Background The regrowth of amputated appendage extremities and the distal tips of digits represent models of tissue regeneration in multiple vertebrate taxa. In humans, digit tip injuries, including traumatic amputation and crush injuries, are among the most common type of injury to the human hand. Despite clinical reports demonstrating natural regeneration of appendages in lower vertebrates and human digits, current treatment options are suboptimal, and are complicated by the anatomical complexities and functions of the different tissues within the digits. Results: In light of these challenges, we focus on recent advancements in understanding appendage regeneration from model organisms. We pay special attention to the cellular programs underlying appendage regeneration, where cumulative data from salamanders, fish, frogs, and mice indicate that regeneration occurs by the actions of lineage‐restricted precursors. We focus on pathologic states and the interdependency that exists, in both humans and animal models, between the nail organ and the peripheral nerves for successful regeneration. Conclusions: The increased understanding of regeneration in animal models may open new opportunities for basic and translational research aimed at understanding the mechanisms that support limb regeneration, as well as amelioration of limb abnormalities and pathologies. Developmental Dynamics 244:641–650, 2015.