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BACKGROUND Onychoheterotopia, or ectopic nail, is a rare nail condition in which nail growth occurs in areas other than the distal phalanges. The majority of cases in the literature are noted to be congenital; however, acquired cases have less commonly been described following either acute or chronic trauma. METHODS We present a case of acquired onychoheterotopia in a child, with a corresponding literature review of acquired pediatric onychoheterotopia cases for comparison. RESULTS There were a total of 10 cases of acquired onychoheterotopia in pediatric patients in the literature. Including our patient, 81.8% (9/11) developed an ectopic nail on the fingers. Crush injury preceded the ectopic nails in 45.5 % (5/11) of cases. Infection occurred in 27.3% (3/11). CONCLUSIONS Although the incidence and prevalence of acquired onychoheterotopia are unknown, it seems to be an uncommon phenomenon. From our case and others from the literature, there may be associations with crush injury specifically. Further research will be needed to fully elucidate the pathophysiology and risk factors for ectopic nail growth.

Objective To analyze the learning curve experience of hip arthroscopy based on patient demographics, surgical time, portal setup time, and postoperative complications and to find the key point in the learning curve. Methods From May 2016 to February 2019, a prospective study on the learning curve experience of hip arthroscopy was performed in our hospital. We evaluated the first 50 consecutive hip arthroscopy procedures performed by a single surgeon. There were nine females and 41 males with a mean age of 30.8 years. We divide the patients into early group and late group according to the date of their operation, with each group including 25 patients. Data on patient demographics, types of procedure, surgical time, portal setup time, and postoperative complications were collected. Functional scores were assessed with the modified Harris Hip Score (mHHS). Results Patients were followed up for 16.4 months on average (range, 13–27 months). The early group of patients had a mean age of 35.2 years and the late group a mean age of 26.5 years. The most common procedures performed for the early group were debridement (17 patients, 68%), and in the late group, most patients underwent labral repair (18 patients, 72%). Mean total surgical time was 168 min for the early group and 143 min for the late group, and there was no statistically significant difference between two groups. The portal setup time in the early group and late group was 40.2 ± 12.4 min and 18.5 ± 6.2 min, respectively (P, This study analyzed the learning curve experience of hip arthroscopy based on the data of 50 patients, and found that the steep learning curve was mainly caused by the challenging of portal setup and portal‐related complications were more common in the early stage.

INTRODUCTION/AIMS Obesity is a factor contributing to suboptimal improvement of motor function in peripheral nerve disorders. In this study we aimed to evaluate the skeletal muscles during denervation and reinnervation after nerve crush injury in leptin-deficient (ob/ob) mice. METHODS Experiments were performed on the skeletal muscles of the hindlimbs in 20 male ob/ob mice and controls. Characteristics of the gastrocnemius muscles were evaluated by histological analysis, immunohistological analysis, and Sircol-collagen assay after measurement of body weight and wet weight of the skeletal muscles, and by walking track analysis. The sciatic nerve was denervated by crushing with smooth forceps and reinnervation was evaluated. RESULTS Gastrocnemius wet weight was significantly lower in the ob/ob mice than in the control mice. A smaller cross-sectional area of type II fibers and increase of type I fiber grouping of the skeletal muscles was demonstrated in the ob/ob mice. After nerve injury, motor function recovery was equal between the groups but the cross-sectional area of type II fibers was significantly smaller in the ob/ob mice than in control mice at 4 weeks. The denervated muscles showed an increase in collagen deposition in the interstitial space; predominant in the ob/ob mice after nerve injury. DISCUSSION The results of this study suggest that fibrosis in the skeletal muscle of obese patients after nerve injury is prominent, which may impair improvement of muscle function after treatment of peripheral nerve disorders.

Background and objectives Crush injuries and prolonged pressure on muscles lead to bruises and sprains and, in most of the cases, cause distraction of the muscle and release of particles into the blood stream, causing renal and systemic complications in severe cases. Laser photobiomodulation treatment (i.e., laser phototherapy) is a method suggested to decrease the pressure damage in the first 24-48 hours after muscle injury, allowing a faster and more complete physical rehabilitation. We studied the efficacy of non-invasive laser photobiomodulation treatment as an on-site treatment for crush-injured gastrocnemius muscles, developing a moderate muscle crush injury model and aiming at decreasing damage extent while regaining physical competence faster. Study design/materials and methods Muscle crush injury was performed on 30 female Wistar rats using direct pressure for 10 minutes on the gastrocnemius muscle in both left and right hindlimbs. Immediately after the injury, only the left hindlimb were irradiated for 16 minutes (with 780 nm laser with a power of 250 mW, the energy at the target was 240 J, and the fluence was 1019 J/cm2 ) for 1, 3, or 7 consecutive days, and sacrificed accordingly. During the follow-up period, 1, 3, or 7 days, both gastrocnemius muscles (of the treated and untreated hindlimbs) were evaluated for electrophysiology and functionality. Results The laser photobiomodulation treatment showed a significant electrophysiological and functional recovery of the gastrocnemius muscle during the first 3 days after injury, in comparison with the untreated hindlimb. Conclusions These preliminary results are promising, showing a significant effect of the laser photobiomodulation treatment during the first 3 days after the induction of the muscle crush injury, which is the most critical period in the clinical aspect. These findings suggest a therapeutic approach, which may help restore the muscle after crush injury.

Objective The aim of the present study was to summarize the clinical efficacy of three‐dimensional (3D) printing technology combined with the Masquelet technique in the treatment of calcaneal defects. Methods From January 2018 to April 2019, 3D printing combined with induced masquelet technology was used to treat four patients with calcaneal defects, including two men and two women. The patients were aged 22–52 years old, with an average age of 36 years. There were two cases of traffic accident injuries, there was one case of a fall from height, and there was one case of crush injury. CT scans were used to reconstruct the bilateral calcaneus, mirror technology was used to construct the bone defect area, and Materialise 3‐matic software was used to design the calcaneus shaper mold and 3D print the mold. During the operation, the mold was used to shape the bone cement and fill the bone defect. In the second stage, the bone cement was removed and autologous bone was implanted to repair the bone defect. All patients were followed up to observe the effect. Results All four patients were followed up for 14 months (range, 10–18 months). There were three cases of infectious bone defects: two cases of Escherichia coli and one case of Pseudomonas aeruginosa. The 3D printed mold was used to shape the bone cement. During the operation, it was found to have a high degree of matching with the defect area of calcaneus. There is no need to adjust it again, and the wound healed well after the first stage. In the second stage of surgery, it was found that the induced membrane formed was complete and of appropriate size; the bone cement was easily removed during the operation. The fracture healing time was 3–6 months, with an average of 4 months. At the last follow up, there was no pain and the patients walked with full weight bearing. The Maryland score was 94 points (range, 88–98 points); three cases were excellent and one case was good. The AOFAS score ranged from 86 to 98, with an average of 92.8 points; three cases were excellent and one case was good. Conclusion Three‐dimensional printing technology combined with induced membrane technology is an effective approach for treating calcaneal bone defects., a. 3D printed model of the affected side and healthy side. b. Mold design of the shaper. c. Debride the wound to the osteotomy surface and see the seepage of fresh blood. d. The shaper mold will solidify the bone cement. e. The lateral skin flap of the leg repairs the skin defect of the foot. f. Appearance of the last follow‐up.

Background Cavernosal fibrosis, which is induced by cavernosal nerve (CN) injury and progresses with time, is the main cause of cavernosal veno-occlusive dysfunction (CVOD) after radical prostatectomy. Objectives To determine whether daily oral administration of suberoylanilide hydroxamic acid (SAHA; vorinostat) for 5-weeks from the immediate post-injury period after CN injury would rectify CVOD by suppressing cavernosal fibrosis and normalizing HDAC pathway in a rat model of CN crush injury (CNCI) and to compare the results with those obtained using chronic administration of PDE5-inhibitors (a positive control). Methods Fifty-six 12-week-old rats were randomized into the four groups: sham surgery (S), CNCI (I), and CNCI treated with daily administration of 25.0 mg/kg SAHA (V) or 20.0 mg/kg udenafil (P). Group-V and Group-P received the respective treatment for 5-weeks from the following day after CNCI. At 5 weeks after surgery, dynamic infusion cavernosometry (DIC), histological staining, and Western blot analysis were performed. Results Group-I had a significantly decreased papaverine response, higher maintenance rate or drop rate, lower smooth muscle (SM)/collagen ratio, decreased SM content, and increased protein expression of HDAC2, HDAC3, TGF-β1, and collagen-1, compared with Group-S. The three DIC parameters in Group-V and Group-P significantly improved compared to those in Group-I. Except for the maintenance rate, the improvement in papaverine response and drop rate in Group-V was not significantly different from that in Group-P. Group-V and Group-P showed the rectification of SM/collagen ratio and protein expression of TGF-β1 or collagen-1. SM content was improved in Group-P, but not in Group-V. Group-V showed the normalization of protein expression of both HDAC2 and HDAC3, whereas protein expression of only HDAC2 was partially restored in Group-P. Discussion Treatment strategies targeting the HDAC pathway might be helpful to alleviate CVOD induced by CN injury. Conclusions According to our data, chronic administration of SAHA improves post-injury CVOD by suppressing cavernosal fibrosis via rectifying the HDAC/TGF-β1 pathway in nerve-injured rats, comparable to that with PDE5 inhibitors.

Aims The urethral dysfunction produced by a rat model of peripheral neurogenic detrusor underactivity (DU) using pelvic nerve crush (PNC) injury was characterized and then tested with the administration of tadalafil, a phosphodiesterase type 5 (PDE 5) inhibitor. Methods Ten days after producing PNC rats, awake cystometrograms (CMGs) and isovolumetric cystometrograms with urethral perfusion pressure (IC-UPP) measurements were performed. Also, in control rats, IC-UPP was recorded before and after intravenous atropine administration to determine if the reduction of bladder contraction pressure affects urethral relaxation during voiding. Then, CMG and IC-UPP measurements in PNC rats were recorded after intravenous administration of tadalafil. Lastly, real-time polymerase chain reaction was used to measure transcript levels of neuronal nitric oxide synthases (nNOS), endothelial nitric oxide synthases, and PDE 5 in urethral specimens from PNC and control rats. Results PNC rats demonstrated the characteristics of DU in CMG. Also, PNC rats exhibited significant decreases in isovolumetric bladder contraction amplitudes and urethral relaxation. Atropine attenuated the amplitude of isovolumetric bladder contractions; however, atropine did not affect urethral relaxation in control rats. Tadalafil decreased postvoid residual and increased voiding efficiency without changing bladder contraction amplitude in PNC rats. Also, tadalafil improved the amplitude of urethral relaxation during bladder contraction in PNC rats. Urethral nNOS transcript levels were upregulated in PNC rats compared to control rats. Conclusions PNC rats revealed both DU and impaired urethral relaxation. PDE 5 inhibition in PNC rats enhanced urethral relaxation during voiding, resulting in improved voiding efficiency. Thus, urethral dysfunction could be a potential target for the treatment of inefficient voiding associated with neurogenic DU.

OBJECTIVES: To create a rat model for neurogenic detrusor underactivity (DU) by bilateral pelvic nerve crush injury (BPNI) and to study temporal changes in detrusor contractility and morphology. METHODS: Male Sprague-Dawley rats were subjected to BPNI or sham surgery and evaluated 1, 3 and 9 weeks after surgery. Bladder function was determined in vivo by awake cystometry, micturition pattern analysis and 24-hours urine collection. Bladders were harvested for in vitro pharmacological investigation by isometric tension recording. Bladders and major pelvic ganglia were investigated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and histochemistry. RESULTS: Overflow incontinence was observed 1 week after BPNI. At 3 and 9 weeks after BPNI, rats showed a bladder phenotype characteristic for DU with increased post-void residuals, reduced voiding efficiencies and lower maximum pressures. In isolated bladder strips, contractile responses to potassium chloride (KCl), carbachol and α,β-methylene adenosine 5'-triphosphate (α,β-mATP) were preserved. On the other hand, neural induced contractility was reduced after BPNI, in line with reduced expression of protein gene product 9.5 and choline acetyltransferase in the major pelvic ganglion 1 week after BPNI. Bladder-to-body weight ratio and detrusor thickness increased following BPNI, indicating detrusor hypertrophy to compensate for the reduced neural input. CONCLUSIONS: BPNI induces a rat model for neurogenic DU. In this model, the detrusor maintains its contractility but denervation of the detrusor was observed. This article is protected by copyright. All rights reserved. ispartof: BJU Int vol:123 issue:5A pages:E86-E96 ispartof: location:England status: Published online

Fatalities due to animal attacks are rare in forensic medical work but have been known to pose problems due to their potential to mimic homicide. This review summarizes reported cases of fatal attacks by large mammals that inhabit the Nordic wilderness, namely brown bear, moose, wild boar, and wolf, and attempts to elucidate injury patterns that can guide the forensic pathologist to identifying the species and modus operandi of the attacker. A tendency toward a species-specific injury pattern was observed. Injuries by bear and especially wolf are dominated by biting whereas moose and wild boar do not seem to bite their victims. The bear uses its paws, both for hitting, resulting in crush injury and fractures, and clawing with resulting excoriations and possible penetrating injuries. Crush injuries and fractures appear, on the other hand, to be minimal or absent in attacks by wolf and wild boar.

Introduction To restore full function following nerve crush injuries is critical but challenging. In an attempt to develop a viable therapy, we evaluated the effect of rat adipose-derived stem cells (rASC) in 2 different settings of a sciatic crush injury model. Methods In the first group, after 14 days of nerve crush injury, rASCs were injected distal to the lesion under ultrasound guidance. In the other group, alleviation of compression through clip removal (CR) was combined with epineural injection of rASCs. Gait analyses, MRI, gastrocnemius muscle weight ratio (MWR), and histomorphometry were performed for outcome analysis. Results CR combined with rASC injection resulted in less muscle atrophy, as evidenced by MWR. These findings are further supported by better functional and anatomical outcomes. Discussion Animals treated with CR and epineural stem cell injection showed enhanced anatomical and functional recovery. Muscle Nerve 58: 566-572, 2018.

Objective To describe the clinical course and successful management of a dog with crush syndrome, rhabdomyolysis, myoglobinuria, and associated acute kidney injury (AKI). Case summary An 8-year-old female, neutered, mixed-breed dog was referred to the Veterinary Teaching Hospital due to crush injury and suspected AKI. Blood tests and urinalysis showed markedly increased serum creatine kinase activity, myoglobinuria, and AKI. The dog was managed successfully with intermittent hemodialysis, and completely recovered. New or unique information provided This is the first report of a dog with crush syndrome with secondary myoglobinuria and AKI.

Aims To produce an animal model of peripheral neurogenic detrusor underactivity (DU) and to evaluate the effect of TRPV4 receptor activation in this DU model. Methods In female Sprague-Dawley rats, bilateral pelvic nerve crush (PNC) was performed by using sharp forceps. After 10 days, awake cystometrograms (CMG) were recorded in sham and PNC rats. A TRPV4 agonist (GSK 1016790A) with or without a TRPV4 antagonist (RN1734) were administered intravesically and CMG parameters were compared before and after drug administration in each group. The TRPV4 transcript level in the bladder mucosa and histological changes were also evaluated. Results In CMG, PNC rats showed significant increases in intercontraction intervals (ICI), number of non-voiding contractions (NVCs), baseline pressure, threshold pressure, bladder capacity, voided volumes, and post-void residual (PVR) compared to sham rats. Contraction amplitude and voiding efficiency were significantly decreased in PNC rats. In PNC rats, intravesical application of GSK1016790A (1.5 μM) significantly decreased ICI, bladder capacity, voided volume, and PVR without increasing NVCs, and these effects were blocked by RN1734 (5.0 μM). In contrast, 1.5 μM GSK1016790A had no significant effects on CMG parameters in normal rats. TRPV4 expression within the bladder mucosa of PNC rats was increased in association with urothelial thickening. Conclusions Rats with bilateral PNC showed characteristics of DU, and this model seems appropriate for further evaluation of peripheral neurogenic mechanisms of DU. Also, TRPV4 receptors, the activation of which reduced bladder capacity and PVR, could be a target for DU treatment.

The aim of this study was to investigate the potential effect and mechanism of action of MANF in attenuating neuronal apoptosis following t-SCI. A clip compressive model was used to induce a crush injury of the spinal cord in a total of 230 rats. The Basso, Beattie, and Bresnahan (BBB) score, spinal cord water content, and blood spinal cord barrier (BSCB) permeability were evaluated. The expression levels of MANF and its downstream proteins were examined by western blotting. Immunofluorescence staining of MANF, NeuN, GFAP, Iba-1, cleaved caspase-3, and TUNEL staining were also performed. Cells were counted in six randomly selected fields in the gray matter regions of the sections from two spinal cord sites (2 mm rostral and caudal to the epicenter of the injury) per sample. A cell-based mechanical injury model was also conducted using SH-SY5Y cells. Cell apoptosis and viability were assessed by flow cytometry, an MTT assay, and trypan blue staining. Subcellular structures were observed by transmission electron microscopy. MANF was mainly expressed in neurons. The expression levels of MANF, and its downstream target, p-Akt, were gradually increased and after t-SCI. Treatment with MANF increased Bcl-2 and decreased Bax and CC-3 levels; these effects were reversed on treatment with MK2206. The BBB score, spinal cord water content, and BSCB destruction were also ameliorated by MANF treatment. MANF decreases neuronal apoptosis and improves neurological function through Akt/MDM-2/p53 pathway after t-SCI. Therefore, MANF might be a potential treatment for patients with t-SCI.© 2018 BioFactors, 2018.

Vascular endothelial growth factor (VEGF) represents one of the main factors involved not only in angiogenesis and vasculogenesis but also in neuritogenesis. VEGF plays its function acting via different receptors: VEGF receptor1 (VEGFR-1), VEGF receptor2 (VEGFR-2), VEGF receptor3 (VEGFR-3), and co-receptors Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2). This study reports on the first in vivo analysis of the expression of VEGF and VEGF family molecules in peripheral nerve degeneration and regeneration: for this purpose, different models of nerve lesion in rat were adopted, the median nerve crush injury and the median nerve transaction followed or not by end-to end microsurgical repair. Results obtained by real time polymerase chain reaction showed that VEGF and VEGF family molecules are differentially expressed under regenerating and degenerating condition, furthermore, in order to study the modulation and involvement of these factors in two different regenerative models, crush injury and end-to-end repair, protein expression analysis was evaluated. In addition, immunohistochemical analysis allowed to state a glial localization of VEGF and VEGFR-2 after peripheral nerve crush injury. Finally in vitro assay on primary Schwann cells culture show that VEGF165 stimulation increases Schwann cells migration, a major process in the promotion of neurite outgrowth. Anat Rec, 301:1646-1656, 2018. © 2018 Wiley Periodicals, Inc.

One-stage reconstruction of composite bone and soft-tissue defects in the forearm remains a tough challenge. Here, we present a case of reconstruction of complex tissue defect at forearm with a chimeric flap consisting of a sural neurocutaneous flap and a fibular graft. A 61-year-old man suffered from a machine crush injury in his left forearm, resulting in a complex tissue defect including extensive dorsomedial soft-tissue, digit extensor muscles of 2-4 fingers, the muscle flexor carpi ulnaris, the ulna bone with 5.5 cm in length, segmental injuries of ulna nerve and vessels, and the radius fracture. The defects were reconstructed by a modified chimeric flap, in which the sural neurocutaneous flap supplied by a peroneal perforator was used to repair the soft-tissue defect and the vascularized fibular graft was used to repair the ulna defect. The two components were supplied by the peroneal vessels. The ulnar nerve defect was bridged by a sural nerve graft. The venous congestion caused by thrombosis was observed at 24 hours postoperatively. After the venous anastomosis was reperformed, the flap survived completely without other complications. Bone healing was achieved at the 7-month follow-up. The index and middle fingers reached nearly full range of motion, while the ranges of motion of metacarpophalangeal joint of the ring and little fingers were less than 60 degrees. The results showed that the modified chimeric flap may be an option for reconstruction of complex tissue defect in the forearm.

The acceleration of nerve regeneration remains a clinical challenge. We previously demonstrated that transcutaneous CO2 application using a novel hydrogel increases the oxygen concentration in local tissue via an "artificial Bohr effect" with the potential to prevent muscle atrophy. In this study, we investigated the effect of transcutaneous CO2 administration on limb function after peripheral nerve injury in a rat sciatic nerve injury model. In total, 73 Sprague-Dawley rats were divided into a sham group, a control group (crush injury to sciatic nerve and no treatment) or a CO2 group (crush injury with transcutaneous CO2 application). CO2 was administered percutaneously for 20 min five times per week. Scores for the sciatic function index and pinprick test were significantly higher in the CO2 group than control group. The muscle wet weight ratios of the tibialis anterior and soleus muscles were higher in the CO2 group than control group. Electrophysiological examination showed that the CO2 group had higher compound motor action potential amplitudes and shorter distal motor latency than the control group. Histological examination of the soleus muscle sections at postoperative week 2 showed shorter fiber diameter in the control group than in the CO2 group. The mRNA expression of Atrogin-1 and MuRF-1 was lower, mRNA expression of VEGF and myogenin and MyoD was higher in CO2 group at postoperative week 2 compared to the control group. Clinical significance Transcutaneous CO2 application has the therapeutic potential to accelerate the recovery of muscle atrophy in peripheral nerve injury. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1653-1658, 2018.

Peripheral nerve injuries constitute a significant medical problem and the recovery is critically dependent on post-injury treatment. In this study, following sciatic nerve crush, we investigated the effects of a 4-week endurance training program (ET) and balance and coordination training program (BCT) on the ultrastructural features of the sciatic nerve and soleus muscle. The animals were randomly divided into Sham, non-trained (NT), ET, and BCT groups each of which included three animals. Ultra-thin cross and longitudinal sections (70-85 nm) were digitized and analyzed comparatively. The electron micrographic analysis of the sciatic nerve showed similar organelles features in the injury groups (myelin debris and swelling mitochondria). Nonetheless, the ET group presented better ultrastructural features as demonstrated by the greater predominance of rounded fibers and more defined organization in the myelinated axon bundles. In the soleus muscle's analyses, the injured groups demonstrated similar organelles' features (nucleus contained highly heterochromatic nuclei and smaller mitochondria). However, ET and BCT groups showed apparently enlarged myofibril cross-sectional areas and less collagen around muscle fibers, although, the ET group displayed reduced intermyofibrillar spaces and more closely aligned myofilaments when compared with the BCT group. Based on electron micrographic analysis, our findings suggest the presence of ultrastructural differences between the Sham, NT, and the trained groups. Therefore, exercise type seems to be responsible for producing some different positive features in the trained groups, while ET seems to have a more pronounced influence on the ultrastructural features of the sciatic nerve and the soleus muscle after a crush injury. Anat Rec, 300:1654-1661, 2017. © 2017 Wiley Periodicals, Inc.

Objective Facial nerve dysfunction can vary in severity and recovery is dependent on the character of the injury. N-acetyl-cysteine prevents oxidative stress and cellular damage, and its use in the setting of nerve dysfunction from crush injury has not yet been established. In this study, rats with facial nerve crush injury will be treated with n-acetyl-cysteine or control and functional recovery and electrophysiologic outcome will be compared. Study design Prospective, randomized animal study. Methods Twenty-four Wistar rats underwent unilateral facial nerve crush injury. Rats were implanted with a subcutaneous osmotic pump filled with saline (n = 12) or n-acetyl-cysteine 50 mg/kg/day (n = 12). Functional and electromyographic recovery was recorded at two and four weeks postoperatively. Results When compared to untreated rats, n-acetyl-cysteine treated rats had a greater electromyography amplitude recovery at 2 weeks with regard to eye blink (p=0.006) but not vibrissae function. At four weeks, the electromyography amplitude recovery of the vibrissae function was greater in n-acetyl-cysteine treated rats (P=0.001), but the amplitude recovery difference in eye blink was only marginally significant between groups (p=0.07). The functional score was higher in n-acetyl-cysteine-treated rats than in untreated rats at all of the time points. Conclusion This study demonstrated that n-acetyl-cysteine facilitated facial nerve recovery with improved functional and electromyography outcomes in the setting of crush injury. Level of evidence NA.

Mutilated hand injuries are a profound challenge to the plastic surgeon, and such injuries often lead to limb loss and severe functional impairment. Hyperbaric oxygen therapy (HBOT) appears to counteract tissue hypoxia and stimulate acute wound healing. This study was performed to evaluate the efficacy of HBOT as an adjunctive therapy in patients with a mutilated hand injury. Between January 2006 and December 2014, 45 patients with a mutilated hand injury were enrolled. After reconstruction or revascularisation, patients underwent 120 minutes of HBOT with oxygen at 2·5 atmospheres absolute while breathing 100% oxygen. Outcomes such as amputee survival and surgery-related complications were recorded. The patients were 38 men and 7 women with average age of 37·2 years (range 18-62). The mean defect area was 131·5 cm2 (range 40-300). Most patients experienced a pure crush injury (53%). The average number of operations from the initial debridement to the first reconstruction was 3·8 (range 1-6). A total of 33 patients (73%) underwent replantation during the initial reconstruction. For flap coverage, most patients received a free flap using an anterolateral thigh flap (18 patients) or local flap using an abdomen/groin flap (nine patients). The average time from the first reconstruction or revascularisation to the first HBOT was 6·5 hours (range 2-12). The average number of HBOT sessions was 9·1 (range 6-14 sessions). The survival rate of the replanted fingers was 81%, and the survival rate of the palms was 100%. Most complications in the initial reconstruction involved partial loss of an avulsed flap, and most complications in the chronic stage (≥3 months) involved scar contracture. When combined with delicate microsurgery, early intervention using adjunctive HBOT was effective in preserving partially viable tissue and restoring hand function in patients with a mutilated hand injury.

Background Peripheral nerve injury (PNI) causes motor and sensory defects, has strong impact on life quality and still has no effective therapy. Miconazole is one of the most widely used antifungal drugs; the aims of the study were to investigate the effects of miconazole during sciatic nerve regeneration in a mouse model of sciatic nerve crush injury. Methods We established peripheral nerve crush model and investigated the effects of miconazole by multiple aspects. We further studied the potential mechanism of action of miconazole by Western blotting, fluorescence immunohistochemistry, and PCR analysis. Results Miconazole improves the symptoms of crushed nerve by improving inflammatory cell infiltration and demyelinating myelin of sciatic nerve. Affected by miconazole, the proportion of inflammatory M1 macrophages in the distal part of the sciatic nerve was reduced, and the proportion of anti‐inflammatory M2 macrophages was increased. Finally, the neuroprotective properties of miconazole may be regulated by the nuclear factor (NF)‐κB pathway. Conclusions Our data suggest that miconazole can effectively alleviate PNI, and the mechanism involves mediating a phenotype change of M1/ M2 macrophages. Thus, miconazole may represent a potential therapeutic intervention for nerve crush injury., Miconazole protects against sciatic nerve crush injury. Miconazole promotes M2 macrophage polarization in vivo and in vitro. Miconazole‐related protection is mediated by the NF‐κB pathway.

INTRODUCTION Erythropoietin (EPO) has been identified as a neuroregenerative agent. We hypothesize that it may accelerate recovery after crush injury and may vary with crush severity. METHODS Mice were randomized to mild, moderate, or severe crush of the sciatic nerve and were treated with EPO or vehicle control after injury. The sciatic function index (SFI) was monitored over the first week. Microstructural changes were analyzed by immunofluorescence for neurofilament (NF) and myelin (P0 ), and electron microscopy was used to assess ultrastructural changes. RESULTS In moderate crush injuries, EPO significantly improved SFI at 7 days post-injury, an effect not observed with other severity levels. Increases in the ratio of P0 to NF were observed after EPO treatment in moderate crush injuries. Electron microscopy demonstrated endothelial cell hypertrophy in the EPO group. CONCLUSIONS EPO accelerates recovery in moderately crushed nerves, which may be through effects on myelination and vascularization. Injury severity may influence the efficacy of EPO. Muscle Nerve 56: 143-151, 2017.

The present work aimed at analyzing the effects of melatonin on scar formation after spinal cord injury (SCI). Upregulation of reactive astrocyte under SCI pathological conditions has been presented in several studies. It has been proved that the crucial factor in triggering this upregulation is proinflammatory cytokines. Moreover, scar formation is an important barrier to axonal regeneration through the lesion area. Melatonin plays an important role in reducing inflammation, but its effects on scar formation in the injured spinal cord remain unknown. Hence, we used the model of severe crush injury in mice to investigate the effects of melatonin on scar formation. Mice were randomly separated into four groups; SCI, SCI+Melatonin 1 (single dose), SCI+Melatonin 14 (14 daily doses), and control. Melatonin was administered by intraperitoneal injection (10 mg/kg) after injury. Immunohistochemical analysis, Western blot, and behavioral evaluation were used to explore the effects of melatonin after SCI for 14 days. The melatonin-treated mice presented higher expression of neuronal markers (P

Purpose To determine the role of diffusion tensor imaging (DTI) metrics as biomarkers for the therapeutic effects of mesenchymal stem cells (MSCs) in acute peripheral nerve injury. Materials and methods Forty-four adult rats received subepineurial microinjection of MSCs (n = 22) or phosphate buffered saline (PBS, n = 22) 1 week after the sciatic nerve trunk crush injury. Sequential fat-suppressed T2-weighted imaging, T2 measurement, DTI and sciatic nerve functional assessment were performed at a 3.0 Tesla MR unit over an 8-week follow-up, with histological assessments performed at regular intervals. The sciatic nerve function index, T2 value, and DTI metrics, including fractional anisotropy (FA), axial diffusivity, radial diffusivity (RD), and mean diffusivity values of the distal stumps of crushed nerves were measured and compared between the two groups. Results Nerves treated with MSCs showed better functional recovery and exhibited more pronounced nerve regeneration compared with nerves treated with PBS. T2 values in nerves treated with MSCs or PBS showed a similar change pattern (P = 0.174), while FA and RD values in nerves treated with MSCs showed more rapid return (one week earlier) to baseline level than nerves treated with PBS (P = 0.045; 0.035). Nerves treated with MSCs had higher FA and lower RD values than nerves treated with PBS during the period from 2 to 3 weeks after surgery (P ≤ 0.0001, 0.004; P = 0.004, 0.006). Conclusion FA and RD values derived from DTI might be used as sensitive biomarkers for detecting the therapeutic effect of stem cells in acute peripheral nerve crush injuries. Level of evidence 2 J. Magn. Reson. Imaging 2017;45:855-862.

Vulnerability to accidents characterizes the extremes of life for reasons that may be similar in each age group. Two cases are reported to demonstrate increased risks of entrapment and crushing injury involving the use of electrically controlled beds/tables. Case 1: A frail 98-year-old woman with a history of dementia suffered a lethal crush injury to her head when she fell out of bed and accidentally activated its lowering mechanism. Case 2: An 18-month-old girl suffered a lethal crush injury to her head when she became trapped under a lowered electric massage table. Common devices may be dangerous if individuals do not have the mental or physical capabilities to deal with them. The forensic assessment of such deaths involves an evaluation of the neurocognitive level and physical strength of the decedent as documented in previous clinical assessments, in addition to a careful examination of the structure and function of the bed/table.

Objectives/Hypothesis To examine and compare the neuroprotective effects of dexamethasone, oxytocin, and resveratrol administration on regeneration after facial nerve crush injury in a rat model. Study Design Prospective, randomized, controlled animal study. Methods A crush-type facial nerve injury was performed on the right side of all rats (injury group [IG]), whereas there was no injury on the left side (sham group [SG]). These main groups were divided into five subgroups: 1) no medicine (control); 2) physiological serum; 3) dexamethasone; 4) oxytocin; and 5) resveratrol (Res) administered (intraperitoneal injection) for 28 days. Functional recovery was evaluated by daily eye-blink reflex and facial electromyography. Nerve–muscle degeneration and regeneration, apoptosis, and intercellular connections were evaluated in histopathological and immunohistochemical examinations. Results Recovery time of the postinjury eye-blink reflex demonstrated faster recovery in IG + Res when compared with the other subgroups. In peak-to-peak amplitude values, a significant increase was observed in the dexamethasone (P = 0.007) and oxytocin subgroups (P = 0.004) and was even more apparent in the resveratrol subgroup (P < 0.001). Nerve regeneration is apparent in the resveratrol subgroup. Apoptotic changes were evaluated immunohistochemically with TUNEL and Caspase 3 and 6 antibodies staining. Caspase 3 and 6 immunoexpressions of resveratrol and oxytocin subgroups were moderate when compared with dexamethasone subgroup. Except for the resveratrol subgroup, which had an increase in expression, the majority of subgroups were similar to SG in terms of intercellular connections (Connexin 32 and 43). Conclusion Resveratrol leads to the best outcome after facial nerve crush injury in rats when compared with dexamethasone and oxytocin, even though these agents demonstrate a significant improvement in facial nerve regeneration. Level of Evidence N/A. Laryngoscope, 125:E356–E364, 2015

Dorsiflexor tendons are particularly exposed in crush injury of the foot. Anterior tibialis tendon defects may be responsible for a steppage gait and a drop foot deformity. Drop foot reconstruction is challenging because of the high risk of postoperative adhesions and functional sequelae. In this report, we present the results of the reconstruction of post-injury anterior tibialis tendon defects with chimeric deep inferior epigatric artery perforator (DIEP) free flap associated with a quadriceps osteotendinous graft in two patients. Two men (32-year-old and 19-year-old) presented drop foot deformity with defect of the anterior tibialis tendon secondary to a crush injury. The sizes of the soft tissues defects at the foot dorsum were 24 cm × 8 cm and 20 cm × 8 cm, respectively. The quadriceps osteotendinous grafts were used to reconstruct the anterior tibialis tendon in both patients. The chimeric DIEP free flaps with skin paddles (24 cm × 8 cm and 20 cm × 8 cm) and rectus abdominis fascia (24 cm × 4 cm and 20 cm × 4 cm) were used for reconstruction. The skin component based on a musculocutaneous perforator was used for soft tissue reconstruction of the foot dorsum. The fascial component based on a second perforator was used to create a sliding surface around the osteotendinous graft. Postoperative course was uneventful. Rehabilitation lasted 3 months. The range of ankle movement was measured during 12 months. The first patient recovered 10 degree of dorsiflexion. The second patient recovered 25 degree of dorsiflexion. Walk recovery was satisfying in both patients. The single-stage procedure using the chimeric DIEP free flap may be an option for post-injury drop foot reanimation. Creating a sliding surface around a composite osteotendinous quadriceps graft with a vascularized fascial component avoid postoperative peritendinous adhesions. This technique may improve foot dorsiflexion and walk recovery. © 2015 Wiley Periodicals, Inc. Microsurgery 36:334-338, 2016.

Introduction: The aims of this study were to determine the influences of: (1) timing of nerve decompression; and (2) nerve fiber types on the patterns of nerve conduction studies (NCS) after nerve injury. Methods: Nerve conduction studies (NCS) were performed on 3 models of nerve injury: (1) crush injury due to transient nerve compression (crush group); (2) chronic constriction injury (CCI), or permanent compression (CCI group); and (3) CCI with removal of ligatures, or delayed nerve decompression (De-CCI group). Results: There were distinct patterns of NCS recovery. The crush and De-CCI groups achieved similar motor nerve recovery, better than that of the CCI group. In contrast, recovery of sensory nerves was limited in the CCI and De-CCI groups and was lower than in the crush group. Conclusions: Immediate relief of compression resulted in the best recovery of motor and sensory nerve conduction. In contrast, delayed decompression restored only motor nerve conduction. Muscle Nerve 52: 107–112, 2015

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. © 2015 Wiley Periodicals, Inc.

In this report, we present a case of toe reconstruction with a medial sural artery perforator free flap after failure of replantation. A 35-year-old male suffered a crush injury from a heavy object falling over the left 1st, 2nd, and 3rd toes and underwent microsurgical replantation of the toes at an outside facility. Over the next 2 weeks, ischemic necrosis of all the toes developed. This condition was very frustrating for the patient who had very high expectations of preserving the toes, and also for the surgeon to determine the optimal method to reconstruct the distal foot and toes. After debridement of non-viable tissues, the defect over the toes was resurfaced using a medial sural artery perforator free flap and full thickness skin graft. Subsequently, several minor operations, including interdigitation, excision of neuromas, and defatting procedure were performed to complete his reconstruction. Eighteen months later, the patient had very aesthetically pleasing and fully functional toes. A medial sural artery perforator free flap may be used to repair the soft tissue defect on the toes after failed replantation, and provides sufficient skin. © 2015 Wiley Periodicals, Inc. Microsurgery, 2015.

Objectives/Hypothesis A new treatment for acute unilateral vocal-fold paralysis (UVFP) was proposed in which a drug is injected into the posterior cricoarytenoid muscle (PCA) shortly after nerve injury, before the degree of natural recovery is known, to prevent antagonistic synkinetic reinnervation. This concept was tested in a series of canine experiments using vincristine as the blocking agent. Study Design Animal experiments. Methods Laryngeal adductor function was measured at baseline and at 6 months following experimental recurrent laryngeal nerve (RLN) injuries, including complete transection, crush injury, and cautery. In the treatment animals, the PCA was injected with vincristine at the time of RLN injury. Results Adductor function in the vincristine-treated hemilarynges was significantly improved compared with injury-matched noninjected controls (total n = 43). Transection/repair controls recovered 56.1% of original adductor strength; vincristine-treated hemilarynges recovered to 73.1% (P = 0.002). Cautery injuries also improved with vincristine block (60.7% vs. 88.7%; P = 0.031). Crush injuries recovered well even without vincristine (104.8% vs. 111.2%; P = 0.35). Conclusion These findings support a new paradigm of early, preemptive blockade of the antagonist muscle (PCA) to improve ultimate net adductor strength, which could potentially improve functional recovery in many UVFP patients and avoid the need for medialization procedures. Possible clinical aspects of this new approach are discussed. Level of Evidence N/A. Laryngoscope, 125:655–660, 2015

Objectives/Hypothesis Surgical intervention of the Eustachian tube (ET) has become increasingly common in the past decade, and balloon dilation has shown promising results in recent studies. It is unclear how balloon dilation enhances ET function. Our aim was to evaluate histological changes in the ET's mucosal lumen comparing before balloon dilation, immediately after, and postoperatively. Study Design Case series. Methods Thirteen patients with bilateral ET dysfunction were enrolled. Biopsies of the ET mucosa were obtained just before balloon dilation; immediately after; and in three cases, 5 to 12 weeks postoperatively. Specimens were retrospectively examined under light microscopy by two pathologists blinded to the clinical information and whether specimens were pre- or postballoon dilation. Results Preoperative biopsies were characterized by inflammatory changes within the epithelium and submucosal layer. Immediate response to balloon dilation was thinning of the mucosa, shearing of epithelium and crush injury to the submucosa, especially to lymphocytic infiltrates. Postoperative biopsies demonstrated healthy pseudocolumnar epithelium and replacement of lymphocytic infiltrate with a thinner layer of fibrous tissue. Conclusion Reduction of inflammatory epithelial changes and submucosal inflammatory infiltrate appeared to be the principal result of balloon dilation. The balloon may shear or crush portions of inflamed epithelium but usually spared the basal layer, allowing for rapid healing. Additionally, it appeared to effectively crush lymphocytes and lymphocytic follicles that may become replaced with thinner fibrous scar. Histopathology of the ET undergoing balloon dilation demonstrated effects that could reduce the overall inflammatory burden and may contribute to clinical improvement in ET function. Level of Evidence 4. Laryngoscope, 125:436–441, 2015

Objectives/Hypothesis Intravenous administration of mesenchymal stem cells (MSCs) has been recently shown to enhance functional recovery after stroke and spinal cord injury. The therapeutic properties of MSCs are attributed to their secretion of a variety of potent antiinflammatory and neurotrophic factors. We hypothesize that intravenous administration of MSCs after recurrent laryngeal nerve (RLN) injury in the rat may enhance functional recovery. Study Design Animal Research. Methods Twelve 250-gram Sprague-Dawley rats underwent a controlled crush injury to the left RLN. After confirming postoperative vocal fold immobility, each rat was intravenously infused with either green fluorescent protein-expressing MSCs or control media in a randomized and blinded fashion. Videolaryngoscopy was performed weekly. The laryngoscopy video recordings were reviewed and rated by a fellowship-trained laryngologist who remained blinded to the intervention using a 0 to 3 scale. Results At 1 week postinjury, the MSC-infused group showed a trend for higher average functional recovery scores compared to the control group (2.2 vs 1.3), but it did not reach statistical significance (P value of 0.06). By 2 weeks, however, both groups exhibited complete return of function. Conclusions These pilot data indicate that with complete nerve transection by crush injury of the RLN in rat, there is complete recovery of vocal fold mobility at 2 weeks. At 1 week postinjury, animals receiving intravenous infusion of MSCs showed a trend for greater functional recovery, suggesting a potential beneficial effect of MSCs; however, this did not reach statistical significance. Therefore, no definite conclusions can be drawn from these data and further study is required. Level of Evidence N/A. Laryngoscope, 124:2555–2560, 2014

To investigate the effects of cerebrolysin (Cbl) on optic nerves (ON) and retinal ganglion cells (RGC) in a rat model of ON crush. Rats received intravitreal injection of Cbl (n = 20), intra-ON injection of Cbl (n = 20), intraperitoneal injection (IPI) of Cbl (n = 20), or phosphate buffered saline (PBS; n = 20) every day for 2 weeks after ON crush injury. At 3 weeks post-trauma, RGC density was counted by retrograde labeling with FluoroGold and visual function was assessed by flash visual-evoked potentials. Activities of microglia after insults were quantified by immunohistochemical analysis of the presence of ED1 in the optic nerve. At 3 weeks postcrush, the densities of RGCs in the Cbl-IVI group (1125 ± 166/mm2) and in the Cbl-IPI treatment group (1328 ± 119/mm2) were significantly higher than those in the PBS group (641 ± 214/mm2). The flash visual-evoked potential measurements showed that latency of the P1 wave was significantly shorter in the Cbl-IVI- and Cbl-IPI-treated groups (105 ± 4 ms and 118 ± 26 ms, respectively) than in the PBS-treated group (170 ± 20 ms). However, only Cbl IPI treatment resulted in a significant decrease in the number of ED1-positive cells at the lesion sites of the ON (5 ± 2 cells/vs. 30 ± 4 cells/high-power field in control eyes). Treatment with intra-ON injection of Cbl was harmful to the optic nerve in the crush model. Systemic administration of Cbl had neuroprotective effects on RGC survival and visual function in the optic nerve crush model.

A 66-year-old woman had sustained crush injury 3 hours prior to her presentation to our hospital. The diagnosis was defined as lateral tibial plateau fracture of the right knee (Schatzker III). Supine position was set up and a pad was put under the affected hip. After sterilization of the surgical field the sterilized sheets were placed beneath the leg in order to be higher than the other side. A rolled sheet was put under the knee joint so that the knee joint was flexed around 30° to 40°. After the surgical field was draped the skin was incised. Iliotibial band was incised by blade (not by electrotomy) and sharp dissection was performed in the Gerdy's tubercle. Capsulotomy was made by cutting the tibial meniscal ligament. Then the meniscus was tagged superiorly and the articular surface was clearly visualized. A window was made in the lateral cortex beneath the plateau, so the impacted fragment was elevated through the window. The metaphyseal void was filled by bone allograft. The placement of the raft-screw plate must be ensured that the raft screws passing the plate could purchase the subchondral bone. After perfect placement of the plate was defined, the femoral distractor was removed and the knee joint was relaxed. It was ensured that the alignment of the lower leg was normal, and then the other screws were inserted. Following placing drainage in the wound the iliotibial band was closed and the subcutaneous soft tissue and skin were closed in layer.

AIMS AND OBJECTIVES: To perform a descriptive analysis of crush syndrome patients with extremity injuries, which will be used as a reference for future disasters. BACKGROUND: In disasters like earthquake, cooperation among medical workers is very important for the follow-up and treatment of patients. Knowing the complications that may emerge with the crush syndrome is one of the responsibilities of the nurses. DESIGN: Descriptive analysis. METHODS: The medical records of patients with crush syndrome following the 2011 Van Earthquake were retrospectively reviewed. The results were compared with the current literature. RESULTS: Of the 46 patients with crush syndrome who had extreme trauma, 26 (57%) were men, 20 (43%) were women, and the average age was 38·9 ± 12·5. Fasciotomy was performed in 21 of the patients due to progressive compartment syndromes. Amputations were performed in seven patients who had previously undergone a fasciotomy. Sepsis was observed in seven patients, wound infection in 18, pericardial effusion in three and pleural effusion in two. Additionally, femoral fracture was observed in one patient, tibial fractures in five, haemothorax in three, abdominal traumas in seven and pulmonary embolism in one. CONCLUSION: Wound care and antibiotic treatment are important to prevent infections in crush injury. In addition to this, dehydration and electrocardiography changes in hyperkalaemia are observed in crush syndrome. Nurses have significant responsibilities to follow up these observations and their implications. RELEVANCE TO CLINICAL PRACTICE: The results of this study may provide the basis for developing strategies in future for optimising attempts to rescue and the nurse care planning of survivors with crush injuries and crush syndrome after earthquakes. Language: en

OBJECTIVE: To describe the epidemiology of genitourinary (GU) injury from toilets that present to USA Emergency rooms (ERs). MATERIALS AND METHODS: The National Electronic Injury Surveillance System (NEISS) is a stratified probability sample of hospital ER visits for USA consumer product-related injuries. NEISS was used to estimate total toilet- and toilet seat-related GU injury for the years 2002-2010, as well as to describe demographics and injury characteristics. Analyses were performed using strata, primary sampling units and sample weights to accommodate the complex sample survey design. Data are reported as national estimates with 95% confidence intervals (CIs) provided. RESULTS: In all, 13 175 (95% CI 10 185-16 165) GU injuries related to toilets presented to ERs during 2002-2010. The most common mechanism involved crush from accidental fall of toilet seat, described in 9011 (68.4%, 95% CI 6907-11 115) cases. Most crush injuries were isolated to the penis (98.1%). Of crush injuries, 81.7% occurred in children aged 2-3 years and 99.3% occurred in the home. Crush injuries increased over the period 2002-2010 (P = 0.017) by ≈100 per year, ending with an estimated 1707 (95% CI 1011-2402) by 2010. Most patients who sustained toilet- and toilet seat-related GU injuries were treated in the ER and then discharged. CONCLUSION: While penile crush injury related to a toilet seat is an uncommon mechanism of urological injury in children, the number of incidents appears to be rising. These findings support educational efforts and interventions, such as exchange of heavy toilet seats with slow-close toilet seat technology. Language: en

Adipose tissue-derived stem cells and insulin-like growth factor-1 (IGF-1) have shown potential to enhance peripheral nerve regeneration. The purpose of this study was to investigate the effect of an in vivo biologic scaffold, consisting of white adipose tissue flap (WATF) and/or IGF-1 on nerve regeneration in a crush injury model. Forty rats all underwent a sciatic nerve crush injury and then received: a pedicled WATF, a controlled local release of IGF-1, both treatments, or no treatment at the injury site. Outcomes were the normalized maximum isometric tetanic force (ITF) of the tibialis anterior muscle and histomorphometric measurements. At 4 weeks, groups with WATF had a statistically significant improvement in maximum ITF recovery, as compared to those without (P < 0.05), and there was an increase in myelin thickness and total axon count in the WATF-only group versus control (P < 0.01). Functional and histomorphometric data suggest that IGF-1 suppressed the effect of the WATF. Use of a pedicled WATF improved the functional and histomorphometrical results after axonotmesis in a rat model. IGF-1 does not appear to enhance nerve regeneration in this model. Utilizing the WATF may have a beneficial therapeutic role in peripheral nerve injuries.

Background and Objectives Peripheral nerve function can be debilitated by different kinds of injury. Low-level laser therapy (LLLT) has been used successfully during rehabilitation to stimulate recovery. The aim of this study was to evaluate the effects of LLLT (660 nm, 60 J/cm2, 40 mW/cm2) on acute sciatic nerve injury. Materials and Methods Thirty Wistar male rats were divided into three groups: (1) Normal, intact nerves; (2) I3d, crushed nerves evaluated on Day-3 post-injury; (3) I + L3d, crushed nerves submitted to two sessions of LLLT and investigated at 3 days post-injury. Sciatic nerves were removed and processed for gene expression analysis (real-time PCR) of the pro-inflammatory factors TWEAK, Fn14 and TNF-α and extracellular matrix remodeling and axonal growth markers, such as TIMP-1, MMP-2, and MMP-9. Zymography was used to determine levels of MMP-2 and MMP-9 activity and Western blotting was used to evaluate TNF-α protein content. Shapiro–Wilk and Levene's tests were applied to evaluate data normality and homogeneity, respectively. One-way ANOVA followed by Tukey test was used for statistical analysis with a significance level set at 5%. Results An increase in TNF-α protein level was found in I + L3 compared to Normal and I3d (P

Very limited literature described the use of the free anterolateral thigh (ALT) among other flaps for pediatric lower limb reconstruction. The aim of this study is to present our experience using the free ALT flap for reconstruction of soft tissue defects over the dorsum of the foot and ankle in children. The study included 42 children aged 2.5–13 years with a mean of 6.18 years. Three children had crush injuries while the rest were victims of run over car accidents. All of the flaps were vascularized by at least two perforators; 88.23% were musculocutaneous and 11.77 were septocutaneous perforators. All flaps were raised in a subfascial plane. Initial thinning was performed in five flaps and 35% required subsequent debulking. Mean Flap surface area was 117.11 cm2. The recipient arteries were the anterior tibial artery in 38 cases and posterior tibial artery in four cases. Venous anastomosis was performed to one vena commitant and in nine cases the long saphenous vein was additionally used. Mean ischemia time of the flap was 2 hours while total operative time averaged 6.3 hours. About 41% of donor sites were closed primarily while 59% required skin grafting. Primary flap survival rate was 92.8% (39/42 cases). Three flaps showed venous congestion. After venous reanastomosis, two flaps showed partial loss and one flap was lost completely. Post-operative hospital stay averaged 7.5 days. The free ALT flap could be as safe, reliable, and aesthetically appealing option for foot/ankle resurfacing in children after traumatic soft tissue loss. © 2012 Wiley Periodicals, Inc. Microsurgery, 2013.

Whether post-traumatic regeneration can eventually result in rat peripheral nerve fibers regaining their pretrauma size is still an open question. While it has been shown that, after a sufficient duration in post-traumatic time, the number of regenerated rat peripheral nerve fibers can return to pretrauma numbers and the animal can regain normal prelesion function, no information regarding long-term changes in the size parameters of the regenerated nerve fibers is available. To fill this gap, we have investigated the post-traumatic changes in myelinated axon and nerve fiber diameter, myelin thickness, and g-ratio (the ratio of the inner axonal diameter to the fiber diameter) at three different time points following nerve injury: week-6, week-8, and week-24. A standardized nerve crush injury of the rat median nerve obtained using a nonserrated clamp was used for this study. The results showed that, consistent with previous studies, fiber number returned to normal values at week-24, but both axon and fiber diameter and myelin thickness were still significantly lower at week-24 than prelesion, and the g-ratio, which remained unchanged during the regeneration process, was significantly reduced at week-24 in comparison to the prelesion value. On the basis of these results, the hypothesis that regenerated rat peripheral nerve fibers are able to return spontaneously to their normal pretrauma state, provided there is a sufficiently long recovery time postaxonotmesis, is not supported. V C 2012 Wiley Periodicals, Inc. Microsurgery 32:383–387, 2012.

Schwann cells (SCs) are crucial for peripheral nerve development and regeneration; however, the intrinsic regulatory mechanisms governing post-injury responses are poorly understood. Activation and deacetylation of nuclear factor-κB (NF- κB) in SCs have been implicated as prerequisites for peripheral nerve myelination. Using GFAP-IκBα-dn mice in which NF- κB transcriptional activation is inhibited in SCs we found no discernable differences in the quantity or structure of myelinated axons in adult facial nerves. Following crush injury, axonal regeneration was impaired at 31 days and significantly enhanced at 65 days in transgenic animals. Compact re-myelination and Remak bundle organization were significantly compromised at 31 days and restored by 65 days post injury. Together, these data indicate that inhibition of NF- κB activation in SCs transiently delays axonal regeneration and compact re-myelination. Manipulating the temporal activation of nuclear factor-κB in Schwann cells may offer new therapeutic avenues for PNS and CNS regeneration.

The astrocyte glutamate transporter, GLT1, is responsible for the vast majority of glutamate uptake in the adult central nervous system (CNS), thereby regulating extracellular glutamate homeostasis and preventing excitotoxicity. Glutamate dysregulation plays a central role in outcome following traumatic spinal cord injury (SCI). To determine the role of GLT1 in secondary cell loss following SCI, mice heterozygous for the GLT1 astrocyte glutamate transporter (GLT1+/-) and wild-type mice received thoracic crush SCI. Compared with wild-type controls, GLT1+/- mice had an attenuated recovery in hindlimb motor function, increased lesion size, and decreased tissue sparing. GLT1+/- mice showed a decrease in intraspinal GLT1 protein and functional glutamate uptake compared with wild-type mice, accompanied by increased apoptosis and neuronal loss following crush injury. These results suggest that astrocyte GLT1 plays a role in limiting secondary cell death following SCI, and also show that compromise of key astrocyte functions has significant effects on outcome following traumatic CNS injury. These findings also suggest that increasing intraspinal GLT1 expression may represent a therapeutically relevant target for SCI treatment.

The goal of this study was to provide evidence that melatonin improves muscle healing following blunt skeletal muscle injury. For this purpose, we used 56 rats and induced an open muscle injury. After injury, all animals received either daily melatonin or vehicle solution intraperitoneally. Subsequent observations were performed at day 1, 4, 7, and 14 after injury. After assessment of fast twitch and tetanic muscle force, we analyzed leukocyte infiltration, satellite cell number, and cell apoptosis. We further quantified the expression of the melatonin receptor and the activation of extracellular-signal-regulated kinase (ERK). Chronic treatment with melatonin significantly increased the twitch and tetanic force of the injured muscle at day 4, 7, and 14. At day 1, melatonin significantly reduced the leukocyte infiltration and significantly increased the number of satellite cells when compared to the control group. Consistent with this observation, melatonin significantly reduced the number of apoptotic cells at day 4. Furthermore, phosphorylation of ERK reached maximal values in the melatonin group at day 1 after injury. Additionally, we detected the MT1a receptor in the injured muscle and showed a significant up-regulation of the MT1a mRNA in the melatonin group at day 4. These data support the hypothesis that melatonin supports muscle restoration after muscle injury, inhibits apoptosis via modulation of apoptosis-associated signaling pathways, increases the number of satellite cells, and reduces inflammation.

We sought to determine whether electrical stimu- lation (ES) with subthreshold, continuous, low-frequency impulses is a viable clinical method for improving functional re- covery after facial nerve crush injury. In 10 rabbits, bilateral crush injuries were made on the facial nerve by compression for 30 s with mosquito forceps, causing complete facial paraly- sis. Subthreshold continuous direct current ES with 20-Hz square-wave pulses was applied to the proximal stump on one side for 4 weeks. Vibrissae movement returned significantly ear- lier on the ES side, with a less variable recovery time. Electro- physiologically, the stimulated side had a significantly shorter latency, longer duration, and faster conduction velocity. Light and transmission electron microscopy revealed that the electri- cal stimulation also markedly decreased Wallerian degenera- tion. The average numbers of fluorescent, double-labeled nerve cells were significantly different between the ES and non-ES sides. This study shows that subthreshold, continuous, low-fre- quency ES immediately after a crush injury of the facial nerve results in earlier recovery of facial function and shorter overall recovery time. Muscle Nerve 43: 251-258, 2011

Objective. To evaluate whether a series of pharmacologic agents with potential neuroprotective effects accelerate and/ or improve facial function recovery after facial nerve crush injury. Study Design. Randomized animal study. Setting. Tertiary care facility. Methods. Eighty female Wistar-Hannover rats underwent head restraint implantation and daily conditioning. Animals then underwent unilateral crush injury to the main trunk of the facial nerve and were randomized to receive treatment with atorvastatin (n = 10), sildenafil (n = 10), darbepoetin (n = 20), or a corresponding control agent (n = 40). The return of whisking function was tracked throughout the recovery period. Results. All rats initiated the return of whisking function from nerve crush by day 12. Darbepoetin-treated rats (n = 20) showed significantly improved whisking amplitude and velocity across the recovery period, with several days of significant pairwise differences vs comparable control rats (n = 16) across the first 2 weeks of whisking function return. In contrast, rats treated with sildenafil (n = 10) and atorvastatin (n = 10) did not show significant improvement in whisking function recovery after facial nerve crush compared to controls. By week 8, all darbepoetin-treated animals and comparable nerve crush control animals fully recovered whisking function and were statistically indistinguishable. Conclusion. Among the 3 potentially neuroprotective agents evaluated, only darbepoetin administration resulted in accelerated recovery of whisking parameters after facial nerve crush injury. Further efforts to define the mechanism of action and translate these findings to the use of darbepoetin in the care of patients with traumatic facial paralysis are needed.

Bromelain, an enzyme extracted from the stem of the pineapple plant has been proposed as a treatment for reducing pain and swelling following acute muscle injuries but studies are yet to be done on its effect on tendon healing. This study therefore investigated the effects of bromelain on tenocyte proliferation and the tendon malondialdehyde (MDA) level in the early stage of healing in a crush injury to the Achilles tendon of Sprague-Dawley rats. Twenty four male rats were divided randomly into three groups; groups 2 and 3 had induced crush injury to the left Achilles tendon. Group 1; nil injury and nil treatment, Group 2; nil treatment, Group 3; oral bromelain treatment. Bromelain was given at a dosage of 7 mg/kg body weight daily over the first 14 days post-injury. On day 15 post injury, the animals were killed and the tendons excised and processed for histological study and MDA assay. The results showed a significant increase in the tenocyte population in the bromelain group; p < 0.05. There was, however, no significant difference in the MDA level. Conclusion: Based on this study, 600 GDU bromelain given once daily in acute tendon injury at a dosage of 7 mg/kg promoted healing by stimulating tenocyte proliferation. Copyright © 2010 John Wiley & Sons, Ltd.

This study documents four clinical cases of fatal crush injuries to children between 1.5 and 6 years of age with correlations between modeled stress and clinically observed fracture patterns. The clinical case fractures were concentrated in the basicranium, bridged the impact sites, and traversed the middle cranial fossa in the area of the spheno-occipital synchondrosis. The crushing forces from these cases were recreated on a simplified finite element model of a cranium by applying bilateral pressures to corresponding regions. Numerous trials were run to develop a representative pattern of principal stress directions. In all cases, the highest tensile stresses were located on the basicranium and corresponded to the observed fracture path(s). These results suggest that prefailure stress field diagrams may predict fracture propagation paths, although these will not be exact. Also, these analyses indicate that quasi-static bilateral loading of the cranium may lead to predictable fracture of the basicranium.