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Background and Purpose: Despite the rapidly increasing global burden of ischemic stroke, no therapeutic options for neuroprotection against stroke currently exist. Recent studies have shown that autophagy plays a key role in ischemic neuronal death, and treatments that target autophagy may represent a novel strategy in neuroprotection. We investigated whether autophagy is regulated by carnosine, an endogenous pleiotropic dipeptide that has robust neuroprotective activity against ischemic brain damage., Methods: We examined the effect of carnosine on mitochondrial dysfunction and autophagic processes in rat focal ischemia and in neuronal cultures., Results: Autophagic pathways such as reduction of phosphorylated mammalian target of rapamycin (mTOR)/p70S6K and the conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II were enhanced in the ischemic brain. However, treatment with carnosine significantly attenuated autophagic signaling in the ischemic brain, with improvement of brain mitochondrial function and mitophagy signaling. The protective effect of carnosine against autophagy was also confirmed in primary cortical neurons., Conclusions: Taken together, our data suggest that the neuroprotective effect of carnosine is at least partially mediated by mitochondrial protection and attenuation of deleterious autophagic processes. Our findings shed new light on the mechanistic pathways that this exciting neuroprotective agent influences., (© 2014 American Heart Association, Inc.)

Study Design: Retrospective., Objective: To evaluate the clinical and radiographical results., Summary of Background Data: The evolution of posterior approach for burst fractures was from long-segment to short-segment and then to monosegmental fixation. Decompression of the spinal cord is performed by anterior or posterior approaches. The technique attempts to decompress the spinal cord by a paramedian subpedicle approach, and simultaneous vertebral reconstruction with pile-up titanium spacers (subpedicle decompression and body augmentation [SpBA]) was developed., Methods: Eighty patients with symptomatic single thoracolumbar Magerl incomplete burst fractures were included. After manual reduction, transpedicle body augmentation and shortsegment fixation (TpBA group) were performed in 38 patients and SpBA in 42 cases. The mean follow-up was 52.6 ± 18.7 (TpBA) and 42.1 ± 7.8 (SpBA) months, and the age was 57.9 ± 7.2 and 59.1 ± 8.3 years. Clinical and radiographical outcomes were analyzed., Results: The operation time was 66 ± 11 (TpBA) versus 34.5 ± 5.5 (SpBA) minutes. The initial anterior vertebral correction was 46.8 ± 12.2% (TpBA) versus 53.2 ± 15.0% (SpBA) (P = 0.03) and the final correction was 44.0 ± 10.8% versus 51.5 ± 15.3% (P = 0.01). Initial corrections of the lateral Cobb angle were 22.3° ± 2.6° versus 22.8° ± 2.7° and the final corrections were 19.1° ± 3.4° versus 20.5° ± 2.9°. The VAS score was 7.7 ± 1.2 versus 7.9 ± 1.2 preoperatively and 2.2 ± 0.7 versus 1.8 ± 0.6 (P = 0.02) at the final visit. Seventy-five patients maintained or recovered to Frankel grade E. Three patients in the TpBA group and 2 in the SpBA group improved from grade C to D. Technical complications included 1 root overstretch in the SpBA group and one incomplete decompression in the TpBA group., Conclusion: SpBA is a safe and fast technique to treat Magerl incomplete burst fractures and leads to good clinical results., Level of Evidence: N/A.

Background: Locking proximal humerus plate (LPHP) fixation has recently become available for the treatment of proximal humeral fractures. However, the preliminary results were contradictory. The technical requirements for success when using LPHP remain to be defined. Maybe the approach to the proximal humerus plays an important role, not the implants. We analyzed two surgical approaches to proximal humeral fractures., Methods: Between April 2004 and October 2007, 63 consecutive patients with displaced proximal humeral fractures who underwent LPHP osteosynthesis in our institute were classified to two treatment groups retrospectively: the deltopectoral incision and the deltoid-splitting incision according to surgeon's preference. The Constant and Disabilities of the Arm, Shoulder and Hand scores were recorded for clinical assessment. Quality of reduction, fracture union, and radiographic complications were recorded for radiographic assessment. Electrophysiological abnormalities were also assessed., Results: There were no significant differences between the groups with regard to demographic data, preoperative radiographic findings, and duration of follow-up. There were also no significant differences between the groups with regard to operative time (p = 0.918), blood loss (p = 0.407), hospital stay (p = 0.431), postoperative head-shaft angle (p = 0.769), union time (p = 0.246), final head-shaft angle (p = 0.533), Constant score (p = 0.677), Disabilities of the Arm, Shoulder and Hand score (p = 0.833), radiographic complications (p = 1.000), and presence of electrophysiological abnormalities (p = 0.296). Avascular necrosis of the humeral head was found in three patients, all of whom in the deltopectoral approach group., Conclusion: We found no statistically significant difference in clinical, radiographic, and electrophysiological outcomes between the deltopectoral approach and deltoid-splitting approach while surgical treatment of proximal humeral fractures.

There is accumulating evidence to implicate the importance of N-methyl-d-aspartate (NMDA) receptors to the induction and maintenance of central sensitization during pain states. However, the use of NMDA receptor antagonists can often be limited by serious central nervous system side effects. The development of peripheral NMDA receptor antagonists that do not interfere with central glutamate processing can avoid adverse effects of the central nervous system. RNA interference is an evolutionarily conserved mechanism for silencing gene expression in which a targeted mRNA is degraded by a double-stranded RNA sequence known as a small interfering RNA (siRNA). siRNAs can be derived from short hairpin (sh) RNAs, which can be expressed from plasmids or viral vectors to achieve long-term gene silencing. In this study, we examined the effect of gene silence and antinociception on formalin-induced pain by subcutaneous injection of vector-encoding shRNA targeting the NR1 subunit of the NMDA receptor. The results revealed that subcutaneous injection of vector-expressing NR1 shRNA could effectively diminish the nociception induced by formalin stimuli and inhibit gene expression of NR1 evidenced by a decreased level of mRNA and protein. The effect of antinociception and inhibition of NR1 expression by NR1 shRNA persisted for about 14days. The data suggest that NR1 shRNA has therapeutic potential to provide long-term treatment of pathological pain that is induced or maintained by peripheral nociceptor activity. Subcutaneous injection of NR1 short hairpin RNA has the therapeutic potential of providing long-term treatment of pathological pain that is induced or maintained by peripheral nociceptor activity., (Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Study Design: A retrospective study assessing new adjacent vertebral compression fracture (VCF) after percutaneous vertebroplasty (PV)., Objective: To evaluate the relationship between cement leakage into the disk during initial PV and development of subsequent new adjacent VCF., Summary of Background Data: Cement leakage outside the vertebral body during PV has been reported and usually responds to conservative treatment. Sometimes bone cement may leak into the intervertebral disk and result in painful new adjacent VCF that usually requires another PV for pain relief., Methods: From January 2002 to December 2002, a total of 106 consecutive patients underwent PVs for osteoporotic VCFs. The risk of new fractures of adjacent vertebral bodies, the amount of cement injection, and the duration of development of new adjacent fractures in relation to cement leakage into the disk were retrospectively assessed and statistically compared., Results: New adjacent VCFs occurred in 20 (18.9%) of 106 patients at 22 adjacent vertebral bodies after PVs during at least 24 months of follow-up. The difference in number of new adjacent fractures between both patients and vertebral bodies with cement leakage and those without leakage into the disk were statistically significant (P<0.001 and P<0.001). Amounts of cement injected and duration to development of new adjacent fractures differed between patients with or without cement leakage (P<0.001 and P=0.005, respectively)., Conclusions: PV is a simple and effective, but not risk-free or complication-free procedure for the treatment of osteoporotic VCF. Patients undergoing PV should be informed of the possibility of new adjacent fractures and the higher risk if cement leaks into the disk.

Background: Although numerous animal models for low back pain associated with intervertebral disk (IVD) degeneration have been proposed, insufficient data have been provided to make any conclusions regarding pain. Our aim in this study was to determine the reliability of complete Freund's adjuvant (CFA) injection into the rat spine as an animal model representing human discogenic pain., Methods: We studied IVD degenerative changes with pain development after a 10-microL CFA injection into the L5-6 IVD of adult rats using behavioral, histologic, and biochemical studies. Serial histologic changes were analyzed to detect degenerative changes. Expression of calcitonin gene-related peptide (CGRP), prostaglandin E (PGE), and inducible nitric oxide synthase (iNOS) were determined using immunohistochemistry or real-time polymerase chain reaction as support data for pain development. In addition, CGRP immunoreactivity (ir) at the IVD was considered indirect evidence of neural ingrowth into the IVD., Results: There was a significant increase of the hindpaw withdrawal response in the CFA group until 7 wk postoperatively (P < 0.05). Histologic analyses revealed progressive degenerative changes of the disks without any damage in adjacent structures, including nerve roots. In the CGRP-ir staining study, the bilateral dorsal horns and IVD had positive ir after intradiscal CFA injection. CGRP mRNA expression was increased in the dorsal root ganglion (DRG) at 2 and 4 wk, whereas PGE and iNOS mRNAs were markedly increased at 2 wk. The increment of CGRP expression was higher in allodynic rats compared with nonallodynic rats., Conclusion: Intradiscal CFA injection led to chronic disk degeneration with allodynia, which was suggested by pain behavior and expression of pain-related mediators. The increment of CGRP, PGE, and iNOS also suggest pain-related signal processing between the IVD and the neural pathway in this animal model. This animal model may be useful for future research related to the pathophysiology and development of novel treatment for spine-related pain.

Study Design: A case of inferior vena cava syndrome following percutaneous vertebroplasty is described herein., Objective: To alert clinicians to the potential occurrence of inferior vena cava syndrome following percutaneous vertebroplasty., Summary of Background Data: Vertebroplasty is a less invasive treatment solution for the osteoporotic compression fracture. There complications of the cement leakage would appear to have been rather infrequent. We report a case of inferior vena cava syndrome related to the cement leakage., Methods: A 59-year-old woman underwent percutaneous vertebroplasty for painful T11, L1, L2, and L3 compression fractures, under general anesthesia at a community hospital. A contralateral transpedicular approach was made in order to inject polymethylmethacrylate resin into the fractured vertebra., Results: Just subsequent to surgery, this patient developed dyspnea, arthralgia, myalgia, and progressive right lower-limb pain, redness, and swelling., conservative treatment being then undertaken, albeit in vain. One week after the attempted remediation of this patient's condition, she was transferred to our hospital for further management. After admission, radiography of the patient's lumbar spine (lateral view) revealed multiple cement leakage in the area of the posterior longitudinal ligament and also in the anterior paravertebral area. The abdominal and pelvic CT scan and venography revealed vertebroplasty cement leakage into the lumbar vein, the left renal vein, and the inferior vena cava. Thrombosis at the left common iliac vein and left femoral vein were noted with extension into the inferior part of the inferior vena cava. Intravenous heparin was then administered to our patient for the ensuing 20 days, at which time heparin was replaced by warfarin, in order to attempt to prevent progressive venous thrombosis. The patient's leg edema appeared to improve 10 weeks subsequent to her surgery, she then being able to perambulate using a rigid walker., Conclusion: This case illustrates the need for clinicians to be critically aware of the potential occurrence of inferior vena cava syndrome among patients who have undergone percutaneous vertebroplasty, especially when multiple levels of vertebra are injected as part of the vertebroplasty procedure.

Background: Published reports about treatment of comminuted subtrochanteric fractures in young patients are few. This study compared the effectiveness of biologic plating and intramedullary nailing in the treatment of such fractures., Methods: A prospective, randomized, and nonblinded study was conducted. Closed reduction and fracture osteosynthesis were performed with either a dynamic condylar screw (DCS) or a Russell-Taylor reconstruction nail (RTRN) in all 66 patients. The average age of the patients was 36.1 years. The average follow-up period was 28.1 months., Results: All but two patients had uneventful bone union and the average time to union was 15.1 weeks. One implant failure in the RTRN group and one delayed union in the DCS group required additional surgery to achieve bone union. Shorter fluoroscopic time, reduced blood loss, and fewer patients requiring blood transfusion were found in the DCS group, though the DCS group had a higher hip pain score 2 years postoperatively. Otherwise, the surgical results and functional outcomes were comparable between groups., Conclusions: With the enhanced fixation properties demonstrated in the present study, the DCS proved to be a feasible fixation device for comminuted subtrochanteric fractures in young patients. Our results indicated that intramedullary nailing by a RTRN revealed no advantages over biologic plating by a DCS for treatment of such fractures.

Expansive laminoplasty was developed to achieve posterior spinal cord decompression while preserving cervical spine stability. In the classic Hirabayashi procedure, the lamina door is tethered open by sutures between the spinous process and facet capsule or paravertebral muscle. The authors present a modified technique, which enhances secure fixation and prevents restenosis owing to hinge closure. Twenty-seven patients (7 females, 20 males) with cervical myelopathy secondary to ossification of the posterior longitudinal ligament were enrolled. Each patient underwent unilateral open-door laminoplasty with suture anchor fixation. Tying and fixation of the sutures onto the holed lateral mass screws was used instead of the conventional method. Radiography, magnetic resonance imaging, and computed tomography scanning were used for imaging studies. The Nurick score was used to assess myelopathy severity, whereas the Japanese Orthopedic Association score was adopted to compare clinical outcome before and after surgery. Mean follow-up period was 38 months (range, 18 to 60). Ten patients had 5 levels of decompression (C3-7), and 17 patients had 4 (C3-6, 12 patients; C4-7, 5 patients). All patients experienced functional improvement of at least 1 Nurick score after surgery. The Japanese Orthopedic Association score increased significantly from 7.5+/-3.2 before surgery to 13.2+/-1.6 at final follow-up. Postoperative radiography and computed tomography scan demonstrated significantly increased sagittal diameter and canal expansion. No neurologic deterioration owing to hinge reclosure or major surgery-related complications were observed. In conclusion, unilateral open-door laminoplasty with suture anchor fixation effectively maintains expansion of the spinal canal and resists closure while preserving alignment and stability. This modified technique has a low complication rate and provides marked functional improvement in patients with cervical myelopathy owing to ossification of the posterior longitudinal ligament.

Background: While the treatment for displaced femoral neck fractures in the elderly (Garden types III and IV) is quite clear, the procedure for impacted or undisplaced femoral neck fractures (Garden types I and II) is still a subject of controversy., Methods: Thirty-seven (all >80 years old) patients with undisplaced femoral neck fractures were treated with osteosynthesis by cannulated screws fixation. The clinical outcomes were followed up retrospectively for at least two years., Results: The overall union rate was 94.59% (35 patients) at 6 months after primary internal fixation. The overall success rate was 83.78% (31 patients), and the overall failure rate was 16.22% (6 patients)., Conclusions: Osteosynthesis with cannulated screws fixation is a simple, safe, economical, and reasonably effective procedure for the treatment of undisplaced femoral neck fractures in patients older than 80 years.

Background: Most children with humeral supracondylar fractures can be treated with simple closed reduction and cross-fixation with Kirschner (K)-wires. However, in a small proportion of cases, an acceptable closed reduction cannot be obtained, and open reduction becomes necessary. An alternative to open reduction is the use of a temporary 3-mm K-wire to manipulate and reduce the distal fragment. This report introduces the method of manipulation, as well as indications, and draws comparisons with complete close reduction cases., Methods: Of 118 patients, 76 (64.4%) were managed with the standard closed reduction method and additional K-wire fixation to secure a good alignment (group 1). In the remaining 42 cases (35.6%), acceptable reduction could not be achieved by closed methods alone, and another temporary 3-mm K-wire was used to manipulate the distal fragment. After reduction of the fracture with the additional wire, standard cross K-wires were inserted to stabilize the fracture (group 2). As long as there was contact at the fracture site in cases of humeral supracondylar fracture, the traditional closed method was used easily to achieve excellent restoration. However, for cases in which the fracture site was totally displaced, and contact at the fracture site via traction was unsuccessful, a 3-mm K-wire was used to perform supplemental restoration treatment. All the patients, after the operation, were temporally immobilized with a long-arm splint for about 3 weeks. The fixation K-wires were removed after the radiograph had shown callus formation over the fracture site. Then the operation indications, operation methods and time, complications, and differences in range of motion were analyzed for these two sets of patients., Results: The average group 1 surgery time was 18 minutes (range, 9-32 minutes), whereas the average surgery time for group 2 was 33 minutes (range, 15-45 minutes). Three cases in group 1 were complicated with ulnar nerve injury caused by the fixation wire. There were no ulnar nerve injuries in group 2. However, the ulnar nerve injury complication rates for the two groups (3 in 76 for group 1; 0 in 40 for group 2) did not reach statistical difference (p = 0.5502, Fisher's exact test). The union times for the two groups were almost the same (average, 3 weeks; range, 2-5 weeks). The 3-mm K-wire manipulation reduction cases and the closed reduction cases seemed to yield the same healing results in all aspects, except for the longer surgery time in group 2 (p < 0.0001). Both groups achieved satisfactory results., Conclusions: The closed reduction method should be used for children with humeral supracondylar fractures, whenever possible. The 3-mm K-wire manipulation method reduces the probability that open reduction will be required in some severe cases. This is a simple method without complications. The prognosis is the same as for closed reduction cases.

Study Design: The aim of this case report is to examine the problem of serious pyogenic spondylitis that may follow vertebroplasty., Objectives: To report 1 case of serious pyogenic spondylitis caused by percutaneous vertebroplasty with polymethyl methacrylate., Summary of Background Data: Serious pyogenic spondylitis caused by percutaneous vertebroplasty with polymethyl methacrylate is a rare complication. We herein report a case of pyogenic spondylitis that occurred after the patient had undergone vertebroplasty., Methods: A 78-year-old woman with a T12 osteoporotic compression fracture, and without a magnetic resonance imaging sign of infection, underwent percutaneous vertebroplasty using polymethyl methacrylate without complication. RESULTS.: About 1 month after the operation, the patient was readmitted because of severe backache, and the diagnosis of pyogenic spondylitis was made using radiograph and magnetic resonance imaging. Anterior inter-body fusion with a strut bone graft after debridement and posterior instrumentation were then performed., Conclusions: Vertebroplasty should proceed under sterile conditions. Excluding the possibility of spinal infection before surgery and a detailed evaluation assuring that the patient is without systemic infectious disease before the vertebroplasty procedure is crucial.

Background: Outstanding results have been achieved using vertebroplasty for the treatment of osteoporotic compression spinal fractures, and a number of studies have reported the results from the application of this procedure. This study compared the results of vertebroplasty used at the different stages of injury., Methods: A retrospective study reviewing the period between January 2001 and July 2001 investigated 68 patients who underwent single-level vertebroplasty: 22 patients within 2 weeks of the injury, 22 patients 2 weeks to 2 months after the injury, and 24 patients more than 2 months after the injury. Clinical evaluations compared the results of treatment at different injury stages during a mean follow-up period of 13 months., Results: Although all the patients undergoing vertebroplasty in the acute and subacute stages reported satisfaction within 1 week of the operation, only 72.7% of the acute-stage group reported satisfaction with 24 hours of surgery. Moreover, evidence of cement leakage after vertebroplasty was detected for 27.3% of the acute-stage patients. This percentage significantly higher than for the patients in the subacute and chronic stages. Radiographic examination showed that new, adjacent compression fracture had occurred for 10.3% of the patients, with anterior interbody restabilization occurring for 11.8%., Conclusions: The results for vertebroplasty treatment of osteoporotic compression fractures appear to be injury stage dependent, with patients in the acute-injury stage needing longer recovery times, and with cement leakage quite common. These findings lead to the conclusion that the subacute stage is optimal for vertebroplasty. Furthermore, it is suggested that the use of spinal orthoses and postsurgical supplementation for the bone matrix reduces the risk of new, adjacent compression fractures and increases anterior interbody restabilization. Importantly, the findings suggest that a presurgical magnetic resonance imaging evaluation is an absolute necessity.

Objective: To examine whether electrical acupuncture therapy through adhesive surface electrodes and concomitant auricular acupuncture therapy could improve the neurologic or functional recovery in acute traumatic spinal cord injury patients., Design: A total of 100 acute traumatic spinal cord injury patients with American Spinal Injury Association (ASIA) impairment grading of A and B were recruited into this study. They were randomly divided into the acupuncture and control groups. In the acupuncture group, electrical acupuncture therapy via the adhesive surface electrodes were applied to the bilateral Hou Hsi (SI3) and Shen Mo (B62) acupoints. In auricular acupuncture, four acupoints related to the spinal cord were selected for stimulation at the antihelix, helix, and lower portion of the ear-back areas. Acupuncture therapy was initiated early in the emergency room setting or soon after spinal surgical intervention. Rehabilitation therapy was also provided to the patients during acupuncture therapy. In the control group, only rehabilitation therapy was provided to the patients. Neurologic and functional scores were assessed during the time of admission, hospital discharge, and 1-yr postinjury follow-up., Results: There were significant improvements in neurologic (sensory and motor), functional, and FIM scores in the acupuncture group compared with the initial admission period when assessed during the time of hospital discharge and the 1-yr postinjury follow-up. A greater percentage of patients in the acupuncture group recovered to a higher ASIA impairment grading., Conclusion: The use of concomitant auricular and electrical acupuncture therapies, when implemented early in acute spinal cord injury, can contribute to significant neurologic and functional recoveries.

Background: Nonunion frequently follows distal clavicle fracture. Traditional pinning methods using the through acromioclavicular articulation may result in osteoarthritic changes or ankylosis. This study introduces a direct pinning technique in which the acromioclavicular joint is spared., Methods: Twelve patients with displaced distal clavicle fractures received open reduction and fixation with Kirschner wires (K-wires) and tension-band wires, from May 1996 to March 1997. The indication for surgery was type IIa fracture or fracture with displacement. Unrestricted passive and active range of motion was performed as soon as possible after the operation. Stretching and exertional exercises were permitted after radiographs showed an osseous union and after the implants were removed., Results: Eleven patients achieved osseous union with painless full motion. Union time ranged from 3 to 6 months. One patient suffered from more comminuted fracture because of a fall 2 months after operation. This patient received a revision surgery with distal clavicle resection and coracoclavicle reconstruction. Symptomless ossification around the coracoclavicle ligament was noted on radiographs in one patient. The ossification did not progress after the 9-month follow-up., Conclusion: Edwards reported a rate of 45% delayed union and 30% nonunion in type II fractures. Several techniques had been described in the relevant literature. In our practice, fixation with Kirschner wires and tension-band wires has been successful in the treatment for displaced distal clavicle fracture.