A murine model of large-scale bone regeneration reveals a selective requirement for Sonic Hedgehog.

Building and maintaining skeletal tissue requires the activity of skeletal stem and progenitor cells (SSPCs). Following injury, local pools of these SSPCs become active and coordinate to build new cartilage and bone tissues. While recent studies have identified specific markers for these SSPCs, how they become activated in different injury contexts is not well-understood. Here, using a model of large-scale rib bone regeneration in mice, we demonstrate that the growth factor, Sonic Hedgehog (SHH), is an early and essential driver of large-scale bone healing. Shh expression is broadly upregulated in the first few days following rib bone resection, and conditional knockout of Shh at early but not late post-injury stages severely inhibits cartilage callus formation and later bone regeneration. Whereas Smoothened (Smo), a key transmembrane component of the Hh pathway, is required in Sox9+ lineage cells for rib regeneration, we find that Shh is required in a Prrx1-expressing, Sox9-negative mesenchymal population. Intriguingly, upregulation of Shh expression and requirements for Shh and Smo may be unique to large-scale injuries, as they are dispensable for both complete rib and femur fracture repair. In addition, single-cell RNA sequencing of callus tissue from animals with deficient Hedgehog signaling reveals a depletion of Cxcl12-expressing cells, which may indicate failed recruitment of Cxcl12-expressing SSPCs during the regenerative response. These results reveal a mechanism by which Shh expression in the local injury environment unleashes large-scale regenerative abilities in the murine rib.

A Diagnostic Algorithm to Guide Operative Intervention of Zone 5 Flexor Injuries.

Background: Given the importance of the neurovascular structures in the volar forearm, accurate diagnosis of zone 5 flexor injuries is critical. Purpose: We sought to test the hypothesis that tendinous injury would be more likely in the distal 50% of the forearm and muscle belly injury would be more likely in the proximal 50% of the forearm. Methods: From December 2015 to December 2016, we conducted a prospective clinical study of patients 18 years and older with zone 5 flexor lacerations. We excluded those with concomitant ipsilateral injuries in flexor zones 1 to 4, multiple lacerations in flexor zone 5, prior neurovascular injuries, crush injuries, patients who underwent operative exploration prior to transfer to our facility, and patients who were unable or unwilling to provide consent. Neurovascular and musculotendinous injuries on physical examination were recorded. All patients underwent operative exploration. Physical examination accuracy and the incidence of musculotendinous and neurovascular injury in the distal 50% of the forearm were compared with the proximal 50% of the forearm. Results: The distal 50% of the forearm (group 1, n = 14) had higher probability of tendon injury (64%), whereas lacerations of the proximal 50% of the forearm (group 2, n = 5) did not result in any tendinous injuries. Rather, all patients in group 2 had muscle belly injuries. There was no difference in the rate of neurovascular injury between groups. Physical examination alone was highly accurate in diagnosing nerve injuries (93%-100%) but less accurate in diagnosing arterial injuries (79%-80%) regardless of the location of injury. Conclusions: Due to the lack of tendinous injuries in proximal zone 5 lacerations, along with the accuracy of physical examination in determining the presence of neurovascular injuries, patients with lacerations in the proximal half of the forearm, without evidence of nerve or arterial injury, can likely be observed in lieu of immediate operative exploration.

Risk Factors Associated With Progression to Surgical Release After Injection of Trigger Digits.

INTRODUCTION: The mainstay of trigger finger treatment is a corticosteroid injection of the affected digits and is associated with a very high success rate. However, some patients do not respond to nonsurgical management and undergo subsequent surgical release. The purpose of this study is to investigate the comorbidities that predispose patients to progressing from injection to surgical release. METHODS: Patient data were obtained from a national insurance database. All patients aged 20 years or older who underwent trigger digit injection were included. Any injection that did not specify the digit was excluded. Subsequent procedures, including repeat injection and surgical release, were identified using relevant Current Procedural Terminology codes. A multivariate model was constructed to evaluate potential risk factors for requiring release after prior injection of the same digit. Stepwise backward selection was used to retain significant variables. RESULTS: A total of 42,537 trigger digits were identified in 31,830 patients, most of whom were female. The right hand was affected more commonly than the left. The middle and ring fingers were the most commonly affected digits. Over 80% of all trigger digits underwent only a single injection, and approximately 90% of injected digits did not require subsequent release. In the multivariate model, factors associated with higher risk of release were male sex, involvement of additional digits, multiple injections of the same digit, chronic pulmonary disease, HIV/AIDS, obesity, alcohol abuse, and depression. The model also found small fingers to be less likely to progress to release. DISCUSSION: Patients with the risk factors identified in this study are more likely to progress to surgical release after trigger finger injection. Although prospective studies are required, the information may be beneficial in counseling patients and their treatment options.

Limited potential of AAV-mediated gene therapy in transducing human mesenchymal stem cells for bone repair applications.

Adeno-associated viral vectors (AAV) are unique in their ability to transduce a variety of both dividing and nondividing cells, with significantly lower risk of random genomic integration and with no known pathogenicity in humans, but their role in ex vivo regional gene therapy for bone repair has not been definitively established. The goal of this study was to test the ability of AAV vectors carrying the cDNA for BMP-2 to transduce human mesenchymal stem cells (MSCs), produce BMP-2, and induce osteogenesis in vitro as compared with lentiviral gene therapy with a two-step transcriptional amplification system lentiviral vector (LV-TSTA). To this end, we created two AAV vectors (serotypes 2 and 6) expressing the target transgene; eGFP or BMP-2. Transduction of human MSCs isolated from bone marrow (BMSCs) or adipose tissue (ASCs) with AAV2-eGFP and AAV6-eGFP led to low transduction efficiency (BMSCs: 3.57% and 8.82%, respectively, ASCs: 6.17 and 20.2%, respectively) and mean fluorescence intensity as seen with FACS analysis 7 days following transduction, even at MOIs as high as 106. In contrast, strong eGFP expression was detectable in all of the cell types post transduction with LV-TSTA-eGFP. Transduction with BMP-2 producing vectors led to minimal BMP-2 production in AAV-transduced cells 2 and 7 days following transduction. In addition, transduction of ASCs and BMSCs with AAV2-BMP-2 and AAV6-BMP-2 did not enhance their osteogenic potential as seen with an alizarin red assay. In contrast, the LV-TSTA-BMP-2-transduced cells were characterized by an abundant BMP-2 production and induction of the osteogenic phenotype in vitro (p < 0.001 vs. AAV2 and 6). Our results demonstrate that the AAV2 and AAV6 vectors cannot induce a significant transgene expression in human BMSCs and ASCs, even at MOIs as high as 106. The LV-TSTA vector is significantly superior in transducing human MSCs; thus this vector would be preferable when developing an ex vivo regional gene therapy strategy for clinical use in orthopedic surgery applications.

Ex vivo regional gene therapy with human adipose-derived stem cells for bone repair.

BACKGROUND: The treatment of complex bone loss scenarios remains challenging. This study evaluates the efficacy of ex vivo regional gene therapy using transduced human adipose-derived stem cells (ASCs) overexpressing bone morphogenetic protein-2 (BMP-2) to treat critical-sized bone defects. METHODS: Critical-sized femoral defects created surgically in immunocompromised rats were treated with ASCs transduced with a lentivirus encoding BMP-2 (Group 1, n = 14), or green fluorescent protein (Group 2, n = 5), nontransduced ASCs (Group 3, n = 5), or rhBMP-2 (Group 4, n = 14). At 12 weeks, femurs were evaluated for quantity and quality of bone formation with plain radiographs, micro-computed tomography, histology/histomorphometry, and biomechanical strength testing. RESULTS: Thirteen of 14 samples in Group 1 and all 14 samples in Group 4 showed radiographic healing, while no samples in either Groups 2 or 3 healed. Groups 1 and 4 had significantly higher radiographic scores (p < 0.001), bone volume fraction (BV/TV) (p < 0.001), and bone area fraction (BA/TA) than Groups 2 and 3 (p < 0.001). Radiographic scores, BV/TV, and BA/TA were not significantly different between Groups 1 and 4. No difference with regards to mean torque, rotation at failure, torsional stiffness, and energy to failure was seen between Groups 1 and 4. CONCLUSIONS: Human ASCs modified to overexpress BMP-2 resulted in abundant bone formation, with the quality of bone comparable to that of rhBMP-2. This strategy represents a promising approach in the treatment of large bone defects in the clinical setting. CLINICAL RELEVANCE: Large bone defects may require sustained protein production to induce an appropriate osteoinductive response. Ex vivo regional gene therapy using a lentiviral vector has the potential to be part of a comprehensive tissue engineering strategy for treating osseous defects.

Risk factors associated with neonatal brachial plexus palsy in the United States.

Neonatal brachial plexus palsy (NBPP) is a birth injury that can cause severe functional loss in the affected limb. The purpose of this study was to determine the temporal changes in the national incidence of this condition and whether associated risk factors have changed over time. Children born via vaginal delivery were identified in the Kids' Inpatient Database (KID) from 1997 to 2012, and those with NBPP were identified. The trend in incidence and risk factors were assessed through the study period. The nationwide incidence of NBPP decreased during the study period. Infants with shoulder dystocia, fetal macrosomia, and gestational diabetes had the highest risk of developing NBPP, while multiple birth mates during delivery had a protective effect. Multiple risk factors, including shoulder dystocia, macrosomia, and heavy for dates became less predictive of the development of NBPP over time. Several risk factors predispose children to the development of NBPP, and the effect of these risk factors has been changing. This information can guide obstetric treatment to help prevent NBPP. Level of evidence is diagnostic, level 3.

Review of Internal Radiocarpal Distraction Plating for Distal Radius Fracture Fixation.

Internal radiocarpal distraction plating is a versatile tool in the treatment of distal radius fractures that are not amenable to nonoperative treatment or operative fixation with standard volar or dorsal implants. Internal distraction plates may also be indicated in the setting of polytrauma or osteopenic bone. The plate functions as an internal fixator, using ligamentotaxis to restore length and alignment while providing relative stability for bony healing. The plate can be fixed to either the second or the third metacarpal, and anatomic and biomechanical studies have assessed the strengths and weaknesses of each strategy. This operative fixation technique leads to acceptable radiographic results and functional outcomes. Following fracture union, the plate is removed, and wrist range of motion is resumed.

The Declining Use of Wrist-Spanning External Fixators.

Background: External fixation has been traditionally used to treat comminuted or open distal radius fractures that are not amenable to open reduction internal fixation. This procedure is associated with a relatively high complication rate and has been used with decreasing frequency in recent years. However, trends in external fixation utilization for the treatment of distal radius fractures have not been described. Methods: Using the Nationwide Inpatient Sample, patients with a distal radius fracture treated with external fixation from 2003 to 2014 were identified. The annual incidence was reported, and hospital and demographic variables associated with external fixation use were determined. Results: During the study period, 593 929 patients with a distal radius fracture were identified, of which 51 766 (8.7%) were treated with a wrist-spanning external fixator. Wrist external fixation for the treatment of distal radius fractures declined steadily from 2003 to 2014. In 2003, external fixation use was highest, accounting for 17.4% of distal radius fractures. By 2014, only 4.9% of distal radius fracture were treated with external fixation. During this period, the incidence of distal radius fractures declined by 6.9% while external fixator utilization decreased by 73.7%. Patients receiving an external fixator were more likely to be male, low-income, and treated in a rural, nonteaching, privately owned hospital. Conclusions: External fixator use for the treatment of distal radius fractures steadily declined during the study period. Males and those with lower incomes treated in rural, nonteaching, and privately owned hospitals are more likely to receive external fixation.

Epidemiological and Treatment Trends of Distal Radius Fractures across Multiple Age Groups.

Background The purpose of this study is to assess the epidemiology, population-specific treatment trends, and complications of distal radius fractures in the United States. Methods The PearlDiver database (Humana [2007-2014], Medicare [2005-2014]) was used to access US inpatient and outpatient data for all patients who had undergone operative and nonoperative treatment for a distal radius fracture in the United States. Epidemiologic analysis was performed followed by age-based stratification, to assess prevalence, treatment trends, and rates of complications. Results A total of 1,124,060 distal radius treatment claims were captured. The incidence of distal radius fractures follows a bimodal distribution with distinct peaks in the pediatric and elderly population. Fractures in the pediatric population occurred predominately in males, whereas fractures in the elderly population occurred more frequently in females. The most commonly used modality of treatment was nonoperative; however, the use of internal fixation increased significantly during the study period, from 8.75 to 20.02%, with a corresponding decrease in percutaneous fixation. The overall complication rate was 8.3%, with mechanical symptoms most frequently reported. Conclusions The last decade has seen a significant increase in the use of internal fixation as treatment modality for distal radius fractures. The impetus for this change is likely multifactorial and partly related to recent innovations including volar locking plates and an increasingly active elderly population. The implicated financial cost must be weighed against the productivity cost of maintaining independent living to determine the true burden to the healthcare system.

Carpal Translocation Following Dorsal Bridge Plate Fixation of Distal Radius Fractures: A Cadaveric Study.

Background Dorsal bridge plate fixation is an effective technique for stabilization of highly comminuted, complex distal radius fractures. However, it is unknown whether fixation to the second or third metacarpal is optimal. Given dorsal bridge plating spans the radiocarpal joint, it is unclear if the dorsal spanning plate affects carpal position. This study investigates differences in carpal translocation resulting from bridge plate distal fixation to either the second or third metacarpal. Methods Ten paired cadaveric upper extremities without evidence of gross deformity or prior surgery distal to the elbow were evaluated with three-view wrist fluoroscopic images for baseline radiographic measurements. An unstable distal radius fracture model was created via a volar approach using a 1-cm osteotomy. Following fracture creation, a dorsal bridge plate was applied with random to the second metacarpal on one limb, and the third metacarpal on the contralateral limb. Laterality for distal fixation was chosen randomly. Fluoroscopic images were repeated and radial inclination, radial height, radiocarpal angle, volar tilt, ulnar variance, radiolunate angle, radioscaphoid angle, radial rotation index, and carpal translocation were measured. Results Radial inclination, radial height, radiocarpal angle, volar tilt, ulnar variance, radiolunate angle, and radioscaphoid angle were not statistically different before and after fixation, or when comparing the second or third metacarpal fixation. Additionally, there was no difference in Taleisnik's ulnar translocation index, Chamay's ulnar translation index, or McMurtry's carpal translation index based on which metacarpal was used for distal fixation. Conclusions Dorsal bridge plate fixation of distal radius fractures restores preoperative physiologic measures of the radius, ulna, and carpus. Carpal translocation was similar when comparing distal fixation to the second or third metacarpal in distal radius fractures stabilized with a bridge plate. Level of Evidence This is a Level V, therapeutic study.

Regional gene therapy with 3D printed scaffolds to heal critical sized bone defects in a rat model.

The objective of the present study was to assess the ability of transduced rat bone marrow cells (RBMCs) that overexpress BMP-2 loaded on a three-dimensionally (3D) printed scaffold to heal a critical sized rat femoral defect. Tricalcium phosphate (TCP) scaffolds were 3D printed to fit a critical sized rat femoral defect. The RBMCs were transduced with a lentiviral (LV) vector expressing BMP-2 or GFP. The rats were randomized into the following treatment groups: (1) RBMC/LV-BMP-2 + TCP, (2) RBMC/LV-GFP + TCP, (3) nontransduced RBMCs + TCP, (4) TCP scaffold alone. The animals were euthanized at 12 weeks and evaluated with plain radiographs, microcomputed tomography (micro-CT), histology, histomorphometry, and biomechanically. Each LV-BMP-2 + TCP treated specimen demonstrated complete healing of the femoral defect on plain radiographs and micro-CT. No femurs healed in the control groups. Micro-CT demonstrated that LV-BMP-2 + TCP treated femoral defects formed 197% more bone volume compared to control groups (p < 0.05). Histologic analysis demonstrated bone formation across the TCP scaffold, uniting the femoral defect on both ends in the LV-BMP-2 + TCP treated specimens. Biomechanical assessment demonstrated similar stiffness (p = 0.863), but lower total energy to failure, peak torque, and peak displacement (p < 0.001) of the femurs treated with LV-BMP-2 + TCP when compared to the contralateral control femur. Regional gene therapy induced overexpression of BMP-2 via transduced RBMCs combined with an osteoconductive 3D printed TCP scaffold can heal a critically sized femoral defect in an animal model. The combination of regional gene therapy and 3D printed osteoconductive scaffolds has significant clinical potential to enhance bone regeneration.

Regulated ex vivo regional gene therapy for bone repair using an inducible caspase-9 suicide gene system.

In order to adapt ex vivo regional gene therapy for clinical applications in orthopaedic surgery, safety issues must be considered. In this study we developed a suicide approach using a dual gene expression two step transcriptional amplification lentiviral vector (LV-TSTA) encoding BMP-2 and an inducible caspase 9 (iC9) system that selectively induces apoptosis upon activation with a chemical inducer of dimerization (CID). Transduction of rat bone marrow stromal cells (RBMSCs) with LV-TSTA-iC9/BMP-2 led to abundant BMP-2 production (90.3 ± 7.9 ng/24 h/106 cells) in vitro and stimulated bone formation in a mouse muscle pouch in the absence of CID. Moreover it was shown that CID could be used to selectively induce apoptosis in iC9-transduced cells both in vitro and in vivo. Double exposure to serial dilutions of CID decreased in vitro production of BMP-2 by 85-87% and Luc activity by 97-99% in iC9/BMP-2 or iC9/Luc-transduced cells respectively. Early administration of CID (Days 0-1 post-op) in mice implanted with iC9/BMP-2-transduced RBMSCs was effective in blocking bone formation, indicating that CID was toxic to the transduced cells. In iC9/Luc-implanted mice, late administration of two doses of CID (Days 27-28 post-op) significantly reduced the luciferase signal. The current study provides proof of concept for the potential clinical application of regulated gene therapy to promote bone repair.

Sox9+ messenger cells orchestrate large-scale skeletal regeneration in the mammalian rib.

Most bones in mammals display a limited capacity for natural large-scale repair. The ribs are a notable exception, yet the source of their remarkable regenerative ability remains unknown. Here, we identify a Sox9-expressing periosteal subpopulation that orchestrates large-scale regeneration of murine rib bones. Deletion of the obligate Hedgehog co-receptor, Smoothened, in Sox9-expressing cells prior to injury results in a near-complete loss of callus formation and rib bone regeneration. In contrast to its role in development, Hedgehog signaling is dispensable for the proliferative expansion of callus cells in response to injury. Instead, Sox9-positive lineage cells require Hh signaling to stimulate neighboring cells to differentiate via an unknown signal into a skeletal cell type with dual chondrocyte/osteoblast properties. This type of callus cell may be critical for bridging large bone injuries. Thus despite contributing to only a subset of callus cells, Sox9-positive progenitors play a major role in orchestrating large-scale bone regeneration. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

Increased Pulmonary Complications Associated with Intramedullary Fixation of Intertrochanteric Fractures: An Analysis of 13,276 Hips.

INTRODUCTION: Intramedullary devices are being used more frequently to treat intertrochanteric (IT) femur fractures but without clear benefit in several clinical trials. This study determines differences in complication rates in patients with IT fractures treated with intramedullary versus extramedullary devices. METHODS: Using the National Surgical Quality Improvement Program database, patients aged ≥55 years with an isolated IT fracture and an American Society of Anesthesiologists score of <5 were identified. Thirty-day mortality and perioperative complications were assessed. RESULTS: Extramedullary fixation was performed in 4,392 patients, whereas 8,884 underwent intramedullary fixation. Intramedullary fixation was associated with increased 30-day mortality (odds ratio [OR], 1.18; P = 0.038), ventilator use (OR, 1.57; P = 0.004), transfusion (OR, 1.12; P < 0.001), and deep vein thrombosis (DVT) (OR, 1.45; P = 0.032). Mean postoperative hospital stay was 1 day shorter for the intramedullary group (P < 0.001). After multivariate analysis, ventilator use (OR, 1.59), DVT (OR, 1.44), and transfusion (OR, 1.15) were more common with intramedullary fixation group. DISCUSSION: Intramedullary fixation for IT fractures was associated with an increased risk of pulmonary complications, DVT, and transfusion. Further randomized controlled studies are required to determine the relative safety of intramedullary versus extramedullary implants. LEVEL OF EVIDENCE: Level III, therapeutic, retrospective comparative study.

Patient and Practice Trends in Total Ankle Replacement and Tibiotalar Arthrodesis in the United States From 2007 to 2013.

INTRODUCTION: Both total ankle replacement (TAR) and tibiotalar arthrodesis (TTA) are used in the surgical management of ankle arthritis. Over the past decade, TAR instrumentation, techniques, and implants have improved, making the procedure more reliable and reproducible, thus making TAR more common. METHODS: The Nationwide Inpatient Sample database from 2007 to 2013 was used to obtain data on patients elder than 50 years who underwent either TAR or TTA. Differences in temporal, demographic, and diagnosis trends between TAR and TTA were analyzed. RESULTS: Between 2007 and 2013, 15,060 patients underwent TAR and 35,096 underwent TTA. Patients undergoing TTA had significantly more comorbidities (2.17 versus 1.55; P < 0.001). The share of TAR performed increased significantly from 2007 (14%) to 2013 (45%) (P < 0.001). From 2007 to 2013, we found a 12-fold increase in the odds of having a TAR for patients with posttraumatic osteoarthritis (P < 0.001), a 4.9-fold increase for those with primary osteoarthritis, and a 3.1-fold increase for patients with rheumatoid arthritis (P < 0.001). CONCLUSIONS: Over the past decade, the frequency of TAR has increased, particularly in patients with posttraumatic arthritis and osteoarthritis. Surgeons still perform TAR in healthier patients compared with TTA; however, because surgeons become more experienced with the technique, patients are undergoing TAR at a markedly higher rate. LEVEL OF EVIDENCE: Level III: retrospective comparative study.

Clinical and Radiological Outcomes of Transfibular Total Ankle Arthroplasty.

BACKGROUND:: Ankle arthritis is a highly limiting pathology that causes pain and functional limitation with subsequent deterioration of quality of life. With recent advances in surgical instrumentation and techniques, prosthetic replacement of the ankle has proven to be a valid alternative to arthrodesis with comparable outcomes. The purpose of this study was to evaluate clinical and radiological findings in a transfibular total ankle replacement with follow-up of at least 2 years. METHODS:: This prospective study included 89 patients who underwent transfibular total ankle arthroplasty from May 2013 to February 2016. The mean age was 53.2 ± 13.5 years. All patients were followed for at least 24 months postoperatively with an average follow-up of 42.0 ± 23.5 months. Patients were assessed clinically and radiographically preoperatively and at 6, 12, and 24 months postoperatively. RESULTS:: At 24 months postoperatively, patients demonstrated statistically significant improvement in the American Orthopaedic Foot & Ankle Society (AOFAS) Ankle Hindfoot Score from 33.8 ± 14.3 to 88.5 ± 6.6 ( P < .001), visual analog scale (VAS) from 80.5 ± 17.0 to 14.1 ± 9.2 ( P < .001), and Short Form-12 Physical and Mental Composite Scores from 29.9 ± 6.7 and 43.3 ± 8.6 to 47.0 ± 7.6 and 53.3 ± 8.1, respectively ( P < .001). In addition, ankle dorsiflexion and plantarflexion improved from 6.2 ± 5.5 and 9.6 ± 5.8 degrees to 24.2 ± 7.9 and 18.1 ± 7.6 degrees, respectively ( P < .001). Radiographically, patients demonstrated maintained neutral alignment of the ankle at 24 months. No patient demonstrated any radiographic evidence of tibial or talar lucency at final follow-up. Seven patients underwent reoperation for removal of symptomatic hardware (6 fibular plates, 1 syndesmotic screw); 2 patients experienced delayed wound healing. The first one was treated with plate removal and flap coverage. The second one required fibular plate removal. One patient developed a postoperative prosthetic infection requiring operative debridement, removal of implants, and placement of an antibiotic spacer. CONCLUSION:: This study found that transfibular total ankle replacement was a safe and effective option for patients with ankle arthritis resulting in improvements in patient-reported outcomes, range of motion, and radiographic parameters. However, further studies are required to determine the mid- and long-term performance of these implants. LEVEL OF EVIDENCE:: Level IV, case series.

Trends in Pediatric Traumatic Upper Extremity Amputations.

Background: Traumatic upper extremity amputation in a child can be a life-altering injury, yet little is known about the epidemiology or health care costs of these injuries. In this study, using the Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID), we assess these trends to learn about the risk factors and health care costs of these injuries. Methods: Using the HCUP KID from 1997 to 2012, patients aged 20 years old or younger with upper extremity traumatic amputations were identified. National estimates of incidence, demographics, costs, hospital factors, patient factors, and mechanisms of injury were assessed. Results: Between 1997 and 2012, 6130 cases of traumatic upper extremity amputation occurred in children. This resulted in a $166 million cost to the health care system. Males are 3.4 times more likely to be affected by amputation than females. The most common age group to suffer amputation is in older children, aged 15 to 19 years old. The frequency of amputation has declined 41% from 1997 to 2012. The overwhelming majority of amputations (92.54%) involved digits. Conclusions: Pediatric traumatic amputations of the upper extremity are a significant contribution to health care spending. Interventions and educational campaigns can be targeted based on national trends to prevent these costly injuries.

Cryopreservation of Human Adipose-Derived Stem Cells for Use in Ex Vivo Regional Gene Therapy for Bone Repair.

The development of an ex vivo regional gene therapy clinical pathway using adipose-derived stem cells (ASCs) may require cryopreservation for cell culture, storage, and transport prior to clinical use. ASCs isolated from five donors were transduced with a lentiviral vector containing BMP-2. Three groups were assessed: transduction without cell freezing (group 1), freezing of cells for 3 weeks followed by transduction (group 2), and cell transduction prior to freezing (group 3). Nontransduced cells were used as a control. The cluster of differentiation (CD) marker profiles, cell number, BMP-2 production, and osteogenic potential were measured. The CD marker profile (CD44, CD73, CD90, and CD105) was unchanged after cryopreservation. Cell number was equivalent among cryopreservation protocols in transduced and nontransduced cells. There was a trend toward decreased BMP-2 production in group 3 compared to groups 1 and 2. Osteogenic potential based on Alizarin red concentration was higher in group 2 compared to group 3, with no difference compared to group 1. Freezing ASCs prior to transduction with a lentiviral vector containing BMP-2 has no detrimental effect on cell number, BMP-2 production, osteogenic potential, or immunophenotype. Transduction prior to freezing, however, may limit the BMP-2 production and potential osteogenic differentiation of the ASCs.

Radial Nerve Palsy following Endovascular Embolization of an Arteriovenous Malformation.

Background Arteriovenous malformations (AVMs) are commonly treated using endovascular techniques. Previous nerve palsies after embolization have been reported as isolated case reports, none of which affected the forearm. Case Description A case of acute, transient neuropathy of the radial nerve following embolization of a forearm AVM is described. The patient, an otherwise healthy 27-year-old man, began having symptoms of superficial radial nerve (SRN) and posterior interosseous nerve (PIN) palsies immediately following endovascular embolization. He underwent decompression of the radial nerve within 5 days and was found to have direct compression of the PIN and SRN. The patient recovered completely at the time of his 7-month follow-up. Literature Review Few cases of nerve palsy after endovascular embolization have been reported in the literature. Many are intracranial, but rare instances of peripheral nerve palsy have been reported, including two sciatic nerve and four digital nerve palsies after endovascular embolization. No cases of peripheral nerve palsy in the forearm have been reported. Clinical Relevance We recommend careful consideration of surrounding neural elements at risk for palsy prior to endovascular embolization and detailed discussion with the patient during the informed consent process.