Ten-year outcome of unilateral leg replantation after bilateral lower leg amputation following traumatic injury: A case report.

The absolute indications for lower limb replantation are not unequivocally established; rather, this procedure is still challenging and controversial. We report a case of a young male who underwent bilateral leg amputation, followed by unilateral replantation. The patient demonstrated good 10-year outcomes. A 23-year-old man had both of his lower legs crushed by heavy machinery that fell from the back of a truck, leading to amputation of bilateral lower limbs. Although bilateral amputation was recommended due to severe contusion on both sides, the patient and his family strongly requested replantation of the right leg, and surgery was started approximately 3 h after the injury. In addition to the emergency replantation, six surgeries were performed thereafter. Five months after the first surgery, the patient was fitted with a left lower leg prosthesis and started gait training. He was discharged 8 months later. Ten years after the replantation, the patient is satisfied with his leg. He has a normal gait with a prosthesis and has integrated into society with no functional deficit. There are still no clear standards for replantation after leg amputation, and individual decisions must be made based on the severity of the injury and the patient's general condition. In this case, we respected the patient's strong will to preserve the right leg and decided on the treatment plan. As a result, the patient was highly satisfied, and the spared right leg facilitated the patient's physical and mental recovery.

Minimally Invasive Percutaneous Spinopelvic Fixation for Unstable Pelvic Ring Fracture Performed With the Patient in a Lateral Position.

Spinopelvic fixation provides a strong fixation for unstable pelvic ring fractures. However, the technique is usually performed with the patient in the prone position, with the applied weight on the anterior superior iliac crests aggravating fracture displacement. We developed a novel approach for minimally invasive percutaneous spinopelvic fixation that is performed with the patient in a lateral (side lying) position. We describe the application of our technique for the treatment of a bilateral pelvic ring and acetabulum fracture in a 79-year-old woman injured in a traffic accident. Initial posterior fixation was performed with the patient in the left-side lying position, using bilateral pedicle screws at L3 and L4 and a left sacral-alar iliac screw and 2 right iliac screws inserted under navigation. The lateral and cranial displacement of the right pelvic ring was reduced percutaneously. One week after this initial surgery, we proceeded with an open anterior reduction and internal fixation of the left pelvic ring and acetabulum fracture. The postoperative course was uneventful and clinical outcomes were satisfactory. Reduction of a pelvic ring fracture in a lateral position, with subsequent spinopelvic fixation, is a reasonable option for the treatment of an unstable pelvic ring fracture.

Drug dependence in patients with chronic pain: A retrospective study.

Drug dependence, which can exist concurrently with chronic pain, is seen as one of the major causes of rapidly increasing medical expenses. However, drug dependence in patients with chronic pain has not been evaluated. The aim of this study was to identify the risk factors for drug dependence in patients with chronic noncancer pain.This retrospective study included 151 patients with chronic noncancer pain (43 males, 108 females; mean age, 72 years). Low back pain (LBP) occurred in 96 patients, whereas 22 had shoulder pain, 8 had hip pain, and 77 had knee pain. Patients were divided into drug dependence and nondrug dependence groups based on the Severity of Dependence Scale (SDS) scores. Patients with SDS scores ≥5 and <5 were classified into drug dependence and nondrug dependence groups, respectively. All patients completed self-report questionnaires. Factors that predict drug dependence were identified by performing univariate and multivariate analyses.Sixty (40%) of the 151 patients met the SDS criteria for drug dependence. Significant differences were found between patients with and without drug dependence for the LBP, hip pain, number of medications, and for the Numerical Rating Scale, Pain Disability Assessment Scale (PDAS), Hospital Anxiety and Depression Scale, and Pain Catastrophizing Scale (PCS) scores. Multiple regression analysis identified LBP, hip pain, PCS, and PDAS scores as factors related to drug dependence in patients with chronic noncancer pain.Drug dependence tends to differ in patients based on the location of their chronic pain. Pain catastrophizing and disability indicated a greater tendency for drug dependence. Thus, PCS and PDAS scores are useful screening tools for predicting drug dependence in patients with chronic pain.

An evaluation of anesthetic fade in motor evoked potential monitoring in spinal deformity surgeries.

BACKGROUND: Intraoperative neuromonitoring using motor evoked potentials (MEP) satisfactorily detects motor tract integrity changes during spinal surgery. However, monitoring is affected by "anesthetic fade," in which the stimulation threshold increases because the waveform amplitude decreases with the accumulation of propofol. Therefore, the purpose of this study was to clarify the effect of anesthetic fade on transcranial MEPs by investigating the time-dependent changes of amplitude during spinal deformity surgeries. METHODS: We retrospectively reviewed medical records of 142 spinal deformity patients (66 patients with idiopathic scoliosis, 28 with adult spinal deformities, 19 with neuromuscular scoliosis, 17 with syndromic scoliosis, and 12 with congenital scoliosis). The average age was 28 years (range, 5 to 81 years). MEPs were recorded bilaterally from the abductor digiti minimi (ADM) and abductor hallucis (AH) muscles during spinal deformity surgeries. The Wilcoxon signed-rank test was used to investigate the time-dependent changes of amplitude after propofol infusion to evaluate anesthetic fade effects. RESULTS: The average time to baseline from initial propofol infusion was 113 min (range, 45 to 182 min). In the ADM, the amplitude was 52% at 1 h after initial propofol infusion, 102% at 2 h, 105% at 3 h, 101% at 4 h, 86% at 5 h, and 81% at 6 h. Compared to the 2-h time point, MEP decreased significantly by 16% at 5 h (P < 0.0005) and by 21% at 6 h (P < 0.05). In the AH, the amplitude was 49% at 1 h after initial infusion of propofol, 102% at 2 h, 102% at 3 h, 92% at 4 h, 71% at 5 h, and 63% at 6 h. Compared to the 2-h time point, MEP decreased significantly by 10% at 4 h (P < 0.005), by 31% at 5 h (P < 0.0000005), and by 39% at 6 h (P < 0.05). CONCLUSIONS: MEP amplitude significantly decreased in the upper limbs at 5 and 6 h and in the lower limbs at 4, 5, and 6 h after the initial infusion of propofol, respectively. The influence of anesthetic fade could influence false positive MEPs during long spinal surgeries.

Relationship between Displacement of the Psoas Major Muscle and Spinal Alignment in Patients with Adult Spinal Deformity.

STUDY DESIGN: Cross sectional study. PURPOSE: To clarify the difference in position of the psoas muscle between adult spinal deformity (ASD) and lumbar spinal stenosis (LSS). OVERVIEW OF LITERATURE: Although it is known that the psoas major muscle deviates in ASD patients, no report is available regarding the difference in comparison with LSS patients. METHODS: This study investigates 39 patients. For evaluating spinal alignment, pelvic tilt (PT), pelvic incidence (PI), sacral slope, lumbar lordosis (LL), PI-LL, Cobb angle, and the convex side, the lumbar curves were measured. For measuring the position of the psoas major at the L4/5 disk level, magnetic resonance imaging was used. The displacements of psoas major muscle were measured separately in the anterior-posterior and lateral directions. We examined the relationship between the radiographic parameters and anterior displacement (AD) and lateral displacement (LD) of the psoas major muscle. RESULTS: AD was demonstrated in 15 cases with ASD and nine cases with LSS (p>0.05). LD was observed in 13 cases with ASD and no cases with LSS (p<0.01). The Cobb angle was significantly greater in cases with AD than in those without AD (p=0.04). PT, LL, PI-LL, and Cobb angle were significantly greater in cases with LD (p<0.05). All cases with LD had AD, but no case without AD had LD (p<0.001). The side of greater displacement at L4/5 and the convex side of the lumbar curve were consistent in all cases. CONCLUSIONS: Despite AD being observed in LSS as well, LD was observed only in the ASD group. Radiographic parameters were worse when LD was seen, rather than AD.

miRNA-133a-5p Inhibits the Expression of Osteoblast Differentiation-Associated Markers by Targeting the 3' UTR of RUNX2.

Recent studies have recognized the involvement of microRNAs (miRNAs) in the development of osteoporosis, which regulate the balance between osteogenesis and osteoclasis. In this study, we investigated the regulation by miRNA-133a-5p on the osteoblast differentiation-associated markers in the mouse osteoblast-like MC3T3-E1 cells by RUNX2. First, we manipulated the miRNA-133a level in the MC3T3-E1 cells with 20 or 40 nM miR-133a-5p mimics, miR-133a-5p inhibitor, or scramble miRNA. Then, we quantified with real-time polymerase chain reaction (qRT-PCR) the expression of Collagen I, osteocalcin (OCN), and osteopontin (OPN) in the miR-133a-5p-manipulated MC3T3-E1 cells. And the confocal microscopy was also utilized to confirm the regulation by miR-133a-5p on the expression of the three molecules. We also investigated the extracellular matrix (ECM) mineralization and the alkaline phosphatase (ALP) activity in the miR-133a-5p-manipulated MC3T3-E1 cells. In addition, we explored the possible targeting by miR-133a-5p on RUNX2, which was a well-recognized promoter to osteoblast differentiation, with luciferase reporter, qRT-PCR, and Western blotting assay. Results demonstrated that the miRNA-133a-5p mimics markedly reduced, whereas the miRNA-133a-5p inhibitor significantly promoted the expression of Collagen I, OCN, and OPN, the ECM mineralization, and the ALP activity in MC3T3-E1 cells. The alignment analysis demonstrated a high homology between miRNA-133a-5p and the 3' UTR of RUNX2. Moreover, the luciferase reporter assay demonstrated that miRNA-133a-5p targeted the 3' UTR of RUNX2, and inhibited the expression of RUNX2 in both mRNA and protein levels. In conclusion, we identified the inhibition by miRNA-133a-5p to the expression of osteoblast differentiation markers, to the ECM mineralization, and to the ALP activity in MC3T3-E1 cells, by targeting the 3' UTR of RUNX2. Our study suggests that miRNA-133a-5p might be an important target to inhibit osteoblast differentiation in osteoporosis.

Collagen-Binding Hepatocyte Growth Factor (HGF) alone or with a Gelatin- furfurylamine Hydrogel Enhances Functional Recovery in Mice after Spinal Cord Injury.

The treatment of spinal cord injury (SCI) is currently a significant challenge. Hepatocyte growth factor (HGF) is a multipotent neurotrophic and neuroregenerative factor that can be beneficial for the treatment of SCI. However, immobilized HGF targeted to extracellular matrix may be more effective than diffusible, unmodified HGF. In this study, we evaluated the neurorestorative effects of an engineered HGF with a collagen biding domain (CBD-HGF). CBD-HGF remained in the spinal cord for 7 days after a single administration, while unmodified HGF was barely seen at 1 day. When a gelatin-furfurylamine (FA) hydrogel was applied on damaged spinal cord as a scaffold, CBD-HGF was retained in gelatin-FA hydrogel for 7 days, whereas HGF had faded by 1 day. A single administration of CBD-HGF enhanced recovery from spinal cord compression injury compared with HGF, as determined by motor recovery, and electrophysiological and immunohistochemical analyses. CBD-HGF alone failed to improve recovery from a complete transection injury, however CBD-HGF combined with gelatin-FA hydrogel promoted endogenous repair and recovery more effectively than HGF with hydrogel. These results suggest that engineered CBD-HGF has superior therapeutic effects than naïve HGF. CBD-HGF combined with hydrogel scaffold may be promising for the treatment of serious SCI.

Bone engineering by phosphorylated-pullulan and ß-TCP composite.

A multifunctional biomaterial with the capacity bond to hard tissues, such as bones and teeth, is a real need for medical and dental applications in tissue engineering and regenerative medicine. Recently, we created phosphorylated-pullulan (PPL), capable of binding to hydroxyapatite in bones and teeth. In the present study, we employed PPL as a novel biocompatible material for bone engineering. First, an in vitro evaluation of the mechanical properties of PPL demonstrated both PPL and PPL/ß-TCP composites have higher shear bond strength than materials in current clinical use, including polymethylmethacrylate (PMMA) cement and α-tricalcium phosphate (TCP) cement, Biopex-R. Further, the compressive strength of PPL/ß-TCP composite was significantly higher than Biopex-R. Next, in vivo osteoconductivity of PPL/ß-TCP composite was investigated in a murine intramedular injection model. Bone formation was observed 5 weeks after injection of PPL/ß-TCP composite, which was even more evident at 8 weeks; whereas, no bone formation was detected after injection of PPL alone. We then applied PPL/ß-TCP composite to a rabbit ulnar bone defect model and observed bone formation comparable to that induced by Biopex-R. Implantation of PPL/ß-TCP composite induced new bone formation at 4 weeks, which was remarkably evident at 8 weeks. In contrast, Biopex-R remained isolated from the surrounding bone at 8 weeks. In a pig vertebral bone defect model, defects treated with PPL/ß-TCP composite were almost completely replaced by new bone; whereas, PPL alone failed to induce bone formation. Collectively, our results suggest PPL/ß-TCP composite may be useful for bone engineering.

A novel, visible light-induced, rapidly cross-linkable gelatin scaffold for osteochondral tissue engineering.

Osteochondral injuries remain difficult to repair. We developed a novel photo-cross-linkable furfurylamine-conjugated gelatin (gelatin-FA). Gelatin-FA was rapidly cross-linked by visible light with Rose Bengal, a light sensitizer, and was kept gelled for 3 weeks submerged in saline at 37°C. When bone marrow-derived stromal cells (BMSCs) were suspended in gelatin-FA with 0.05% Rose Bengal, approximately 87% of the cells were viable in the hydrogel at 24 h after photo-cross-linking, and the chondrogenic differentiation of BMSCs was maintained for up to 3 weeks. BMP4 fusion protein with a collagen binding domain (CBD) was retained in the hydrogels at higher levels than unmodified BMP4. Gelatin-FA was subsequently employed as a scaffold for BMSCs and CBD-BMP4 in a rabbit osteochondral defect model. In both cases, the defect was repaired with articular cartilage-like tissue and regenerated subchondral bone. This novel, photo-cross-linkable gelatin appears to be a promising scaffold for the treatment of osteochondral injury.

Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4.

PURPOSE: Bone defects and nonunions are major clinical skeletal problems. Growth factors are commonly used to promote bone regeneration; however, the clinical impact is limited because the factors do not last long at a given site. The introduction of tissue engineering aimed to deter the diffusion of these factors is a promising therapeutic strategy. The purpose of the present study was to evaluate the in vivo osteogenic capability of an engineered bone morphogenetic protein-4 (BMP4) fusion protein. METHODS: BMP4 was fused with a nanosized carrier, collagen-binding domain (CBD), derived from fibronectin. The stability of the CBD-BMP4 fusion protein was examined in vitro and in vivo. Osteogenic effects of CBD-BMP4 were evaluated by computer tomography after intramedullary injection without a collagen-sponge scaffold. Recombinant BMP-4, CBD, or vehicle were used as controls. Expressions of bone-related genes and growth factors were compared among the groups. Osteogenesis induced by CBD-BMP4, BMP4, and CBD was also assessed in a bone-defect model. RESULTS: In vitro, CBD-BMP4 was retained in a collagen gel for at least 7 days while BMP4 alone was released within 3 hours. In vivo, CBD-BMP4 remained at the given site for at least 2 weeks, both with or without a collagen-sponge scaffold, while BMP4 disappeared from the site within 3 days after injection. CBD-BMP4 induced better bone formation than BMP4 did alone, CBD alone, and vehicle after the intramedullary injection into the mouse femur. Bone-related genes and growth factors were expressed at higher levels in CBD-BMP4-treated mice than in all other groups, including BMP4-treated mice. Finally, CBD-BMP4 potentiated more bone formation than did controls, including BMP4 alone, when applied to cranial bone defects without a collagen scaffold. CONCLUSION: Altogether, nanocarrier-CBD enhanced the retention of BMP4 in the bone, thereby promoting augmented osteogenic responses in the absence of a scaffold. These results suggest that CBD-BMP4 may be clinically useful in facilitating bone formation.

Recovery of motor function in patients with subaxial cervical spine injury relevant to the fracture pattern.

In this study, we studied the relationship between fracture patterns and motor function recovery in 70 consecutive patients with cervical spinal cord injury. Fractures were categorized into 6 fracture types and subdivided into stages according to the Allen-Ferguson classification system:compressive flexion (CF), distractive flexion (DF), compressive extension (CE), distractive extension (DE), vertical compression (VC) and lateral flexion (LF). Paralysis was evaluated using the American Spinal Injury Association (ASIA) impairment scale at the time of injury and 3 months afterwards. The residual rate of complete motor palsy (ASIA grade A or B) at the final examination was higher in those patients with DE fractures than those with CF, DF or CE. The final outcomes were as follows. Of the 14 patients who were classified with CF fractures, residual palsy was frequently seen in patients who had stage 5 injury. Of the 27 patients with DF fractures, residual palsy occurred in about half of the patients who had stage 4 or 5 injury. Of the 18 patients with CE fractures, residual palsy occurred in half of the patients with stage 3 injury or higher. Finally, of the 7 patients with DE fractures, the rate of residual palsy was high even for the stage 1 and 2 cases;indeed, all DE patients who had complete motor palsy at the first examination had residual palsy at the final examination. Accordingly, we conclude that motor recovery may be related to fracture pattern.

Motion Induced Artifact Mimicking Cervical Dens Fracture on the CT Scan: A Case Report.

The diagnostic performance of helical computed tomography (CT) is excellent. However, some artifacts have been reported, such as motion, beam hardening and scatter artifacts. We herein report a case of motion-induced artifact mimicking cervical dens fracture. A 60-year-old man was involved in a motorcycle accident that resulted in cervical spinal cord injury and quadri plegia. Reconstructed CT images of the cervical spine showed a dens fracture. We assessed axial CT in detail, and motion artifact was detected.

Upper lumbar pedicle screw insertion using three-dimensional fluoroscopy navigation: assessment of clinical accuracy.

We used a navigation system to insert 128 pedicle screws into 69 vertebrae (L1 to L3) of 49 consecutive patients. We assessed the pedicle isthmic width and the permission angle for pedicle screw insertion. The permission angle is the angle defined by the greatest medial and lateral trajectories allowable when placing the screw through the center of the pedicle. The rate of narrow-width pedicles (isthmic width less than 5 mm) was 5 of 60 pedicles (8%) at L1, 4 of 60 pedicles (7%) at L2, and none (0%) at L3, L4 and L5. The rate of narrow-angle pedicles (a permission angle less than 15 degrees) was 21 of 60 pedicles (35%) at L1, 7 of 60 (12%) at L2, 3 of 60 (5%) at L3, and none (0%) at L4 and L5. Of 128 pedicle screws inserted into 69 vertebrae from L1 to L3, 125 (97.7%) were classified as Grade 1 (no pedicle perforation). In general, the upper lumbar vertebrae have more narrow-width and -angle pedicles. However, we could reduce the rate of pedicle screw misplacement in upper lumbar vertebra using a three-dimensional fluoroscopy and navigation system.

Clinical accuracy of three-dimensional fluoroscopy (IsoC-3D)-assisted upper thoracic pedicle screw insertion.

Correct screw placement is especially difficult in the upper thoracic vertebrae. At the cervicothoracic junction (C7-T2), problems can arise because of the narrowness of the pedicle and the difficulty of using a lateral image intensifier there. Other upper thoracic vertebrae (T3-6) pose a problem for screw insertion also because of the narrower pedicle. We inserted 154 pedicle screws into 78 vertebrae (C7 to T6) in 38 patients. Screws were placed using intraoperative data acquisition by an isocentric C-arm fluoroscope (Siremobile Iso-C3D) and computer navigation. Out of 90 pedicle screws inserted into 45 vertebrae between C7 and T2, 87 of the 90 (96.7%) screws were classified as grade 1 (no perforation). Of 64 pedicle screws inserted into 33 vertebrae between T3 and T6, 61 of 64 (95.3%) screws were classified as grade 1. In this study, we reduced pedicle screw misplacement at the level of the C7 and upper thoracic (T1-6) vertebrae using the three-dimensional fluoroscopy navigation system.

Vertebral rotation during pedicle screw insertion in patients with cervical injury.

BACKGROUND: Cervical pedicle screws, when misplaced, tend to perforate laterally. One of the reasons for lateral perforation is vertebral rotation during screw insertion. However, actual vertebral rotation during pedicle screw insertion is unknown. In this study, we measured vertebral rotation during pedicle screw insertion in patients with cervical injury. METHODS: We inserted 76 pedicle screws into 38 vertebrae (C2 to C7) in 17 patients. All patients had some type of cervical injury. Screws were placed using intraoperative acquisition of data acquired with the isocentric C-arm fluoroscope (Iso-C3D) and computer navigation. We made screw holes using an image-guided awl, and we took images of cervical vertebrae in the neutral and rotational positions using navigation. Images of 76 insertions and rotational positions were taken while each cervical vertebra was under maximum stress at the time we were making the pedicle hole by awl. RESULTS: Average cervical vertebra rotation was 10.6 degrees (range 6 to 17) at C2, 9.1 degrees (5 to 13) at C3, 7.8 degrees (6 to 9) at C4, 6.7 degrees (4 to 11) at C5, 4.9 degrees (2 to 8) at C6, and 2.8 degrees (0 to 4) at C7. Vertebrae in the upper and middle cervical spine rotated more than the lower cervical spine vertebrae. Of the 76 pedicle screws inserted into vertebrae between C2 and C7, 74 screws (97.4%) were classified as grade 1 (no pedicle perforation). CONCLUSIONS: In this study, upper and middle cervical vertebrae in patients with neck injuries rotated more than the lower vertebrae. We should be especially careful of cervical rotation during screw insertion from C2 to C6, so as to prevent vertebral artery injury.