Woo-Kie Min

Combined effects of hematopoietic progenitor cell mobilization from bone marrow by granulocyte colony stimulating factor and AMD3100 and chemotaxis into the brain using stromal cell-derived factor-1α in an Alzheimer's disease mouse model.

Transplantation of bone marrow‐derived stem cells (BMSCs) has been suggested as a potential therapeutic approach to prevent neurodegenerative diseases, but it remains problematic due to issues of engraftment, potential toxicities, and other factors. An alternative strategy is pharmacological‐induced recruitment of endogenous BMSCs into an injured site by systemic administration of growth factors or chemokines. Therefore, the aim of this study was to examine the effects of therapy involving granulocyte colony stimulating factor (G‐CSF)/AMD3100 (CXCR4 antagonist) and stromal cell‐derived factor‐1α (SDF‐1α) on endogenous BM‐derived hematopoietic progenitor cell (BM‐HPC) recruitment into the brain of an Alzheimers disease (AD) mouse model. To mobilize BM‐HPCs, G‐CSF was injected intraperitoneally and boosted by AMD3100. Simultaneously, these mice received an intracerebral injection with SDF‐1α to induce migration of mobilized BM‐HPCs into brain. We found that the memory deficit in the AD mice was significantly improved by these treatments, but amyloid β deposition was unchanged. Interestingly, microglial activation was increased with alternative activation of microglia to a neuroprotective phenotype. Furthermore, by generating an amyloid precursor protein/presenilin 1‐green fluorescent protein (GFP) chimeric mouse, we ascertained that the GFP positive microglia identified in the brain were BM‐derived. Additionally, increased hippocampal neurogenesis and improved memory was observed in mice receiving combined G‐CSF/AMD3100 and SDF‐1α, but not in controls or animals receiving each treatment alone. These results suggest that SDF‐1α is an effective adjuvant in inducing migration into brain of the endogenous BM‐HPCs, mobilized by G‐CSF/AMD3100, and that the two can act synergistically to produce a therapeutic effect. This approach warrants further investigation as a potential therapeutic option for the treatment of AD patients in the future. STEM CELLS 2011;29:1075–1089

Sagittal alignment as a predictor of clinical adjacent segment pathology requiring surgery after anterior cervical arthrodesis

BACKGROUND CONTEXT Postoperative malalignment of the cervical spine may alter cervical spine mechanics and put patients at risk for clinical adjacent segment pathology requiring surgery. PURPOSE To investigate whether a relationship exists between cervical spine sagittal alignment and clinical adjacent segment pathology requiring surgery (CASP-S) following anterior cervical fusion (ACF). STUDY DESIGN Retrospective matched study. PATIENT SAMPLE A total of 122 patients undergoing ACF between 1996 and 2008 were identified, with a minimum of 2 years of follow-up. OUTCOME MEASURES Radiographs were reviewed to measure the sagittal alignment using C2 and C7 sagittal plumb lines, distance from the fusion mass plumb line to the C2 and C7 plumb lines, the alignment of the fusion mass, caudally adjacent disc angle, the sagittal slope angle of the superior end plate of the vertebra caudally adjacent to the fusion mass, T1 sagittal angle, overall cervical sagittal alignment, and curve patterns by Katsuura classification. METHODS A total of 122 patients undergoing ACF between 1996 and 2008 were identified, with a minimum of 1 year of follow-up. Patients were divided into groups according to the development of CASP (control/CASP-S) and by number/location of levels fused. Radiographs were reviewed to measure the sagittal alignment using C2 and C7 sagittal plumb lines, distance from the fusion mass plumb line to the C2 and C7 plumb lines, the alignment of the fusion mass, caudally adjacent disc angle, the sagittal slope angle of the superior end plate of the vertebra caudally adjacent to the fusion mass, T1 sagittal angle, overall cervical sagittal alignment, and curve patterns by Katsuura classification. Appropriate statistical tests were performed to calculate relationships between the variables and the development of CASP-S. No funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this article. RESULTS The groups were similar with regard to demographic and surgical variables. Lordosis was preserved in 82% (50/61) of the control group but in only 66% (40/61) of the CASP-S group (p=.033). More patients with a straight curve pattern developed CASP-S. The distance from the C2 to the C7 plumb line and T1 sagittal slope angle were lower in the CASP-S group with C5-C6 fusions compared with the control group. Also, the distance from C5-C6 fusion mass to C7 plumb line and C7 sagittal slope angle were lower in the CASP-S group with C5-C6 fusions. CONCLUSIONS Our results suggest that malalignment of the cervical spine following an ACF at C5-C6 has an effect on the development of clinical adjacent segment pathology requiring surgery.

Bone Marrow-Derived Mesenchymal Stem Cells Prevent the Loss of Niemann-Pick Type C Mouse Purkinje Neurons by Correcting Sphingolipid Metabolism and Increasing Sphingosine-1-phosphate†‡§

Niemann‐Pick type C (NP‐C) disease exhibits neuronal sphingolipid storage and cerebellar Purkinje neuron (PN) loss. Although it is clear that PNs are compromised in this disorder, it remains to be defined how neuronal lipid storage causes the PN loss. Our previous studies have shown that bone marrow‐derived mesenchymal stem cells (BM‐MSCs) transplantation prevent PN loss in NP‐C mice. The aim of the present study was therefore to examine the neuroprotective mechanism of BM‐MSCs on PNs. We found that NP‐C PNs exhibit abnormal sphingolipid metabolism and defective lysosomal calcium store compared to wild‐type mice PNs. BM‐MSCs promote the survival of NP‐C PNs by correction of the altered calcium homeostasis, restoration of the sphingolipid imbalance, as evidenced by increased sphingosine‐1‐phosphate levels and decreased sphingosine, and ultimately, inhibition of apoptosis pathways. These effects suggest that BM‐MSCs modulate sphingolipid metabolism of endogenous NP‐C PNs, resulting in their survival and improved clinical outcome in mice. STEM CELLS 2010;28:821–83128:821–831

Retrograde nailing with subsequent screw fixation for ipsilateral femoral shaft and neck fractures

IntroductionAlthough ipsilateral femoral shaft and neck fractures are difficult to treat, there is still no consensus on the optimal treatment of this complex injury. We report the results of treating the 17 fractures with a standard protocol of retrograde nailing for diaphyseal fractures and subsequent screw fixation for the femoral neck fractures.Materials and methodsSeventeen injuries (16 patients) sustained femoral shaft fractures, which were treated with retrograde intramedullary nails and subsequent screw fixation. Femoral neck fracture was noted before the operation in all patients except one. A femoral shaft fracture was always addressed first with unreamed retrograde nailing. Then, the femoral neck fracture was treated by cannulated screws or dynamic hip screw according to the level of fracture.ResultsThe average time for union of femoral shaft fractures was 27.3 (14–60) weeks. Nonunion occurred in five patients, who required bone grafts or changes of fixation. The average time for union of femoral neck fractures was 11 (8–12) weeks. All united, except for one case of nonunion with avascuar necrosis, which was a Garden stage IV fracture. Functional results using Friedman–Wyman criteria were good in 16 cases, and fair in one. The only fair result was nonunion of the femoral neck, which had the joint arthroplasty.ConclusionRetrograde nailing of femoral shaft fractures can provide an easy fixation and a favorable result for ipsilateral femoral neck fractures.

Anterior Screw Fixation of Type II Odontoid Fractures in the Elderly

PURPOSE Optimal surgical treatment in elderly patients with type II odontoid fracture is still controversial. The purpose of this study is to investigate the surgical outcomes of anterior screw fixation of type II B odontoid fractures in the elderly. MATERIALS Fifteen patients who had type II B odontoid fracture were treated consecutively by anterior odontoid screw fixation between 2001 and 2005. The patient group comprised 11 men and 4 women. In all patients, 3-D CT reconstructions were checked for accurate diagnosis for type II odontoid fracture. The medical records, plain X-rays, and CT scans of all patients were reviewed and fusion rate, union time, incidence of perioperative complications, neurologic outcome, and mortality were studied. Radiologic and clinical follow-up were performed in all patients. RESULTS All patients were treated with anterior odontoid screw fixation by use of one compression screw. Mean age was 68.9 years (range, 61-78) and mean follow-up was 18.3 months. The overall fusion rate was 77%. If follow-up studies revealed pseudarthrosis, additional dorsal fixation with transarticular C1-C2 screws or C1-C2 posterior screw-rod fixation with bone graft was performed. Mean union time was 17.1 week. CONCLUSIONS The outcome of anterior odontoid screw fixation of type II B odontoid fractures in the elderly is satisfactory. We experienced satisfactory union rates and preserved cervical range of movement without the need of postoperative rigid neck immobilization. The morbidity associated with this procedure was low. We recommend anterior screw fixation as an effective method of treating type II B odontoid fractures in the elderly.

Negative pressure wound therapy for soft tissue injuries around the foot and ankle

BackgroundThis study was performed to evaluate the results of negative pressure wound therapy (NPWT) in patients with open wounds in the foot and ankle region.Materials and methodsUsing a NPWT device, 16 patients were prospectively treated for soft tissue injuries around the foot and ankle. Mean patient age was 32.8 years (range, 3–67 years). All patients had suffered an acute trauma, due to a traffic accident, a fall, or a crush injury, and all had wounds with underlying tendon or bone exposure. Necrotic tissues were debrided before applying NPWT. Dressings were changed every 3 or 4 days and treatment was continued for 18.4 days on average (range, 11–29 days).ResultsExposed tendons and bone were successfully covered with healthy granulation tissue in all cases except one. The sizes of soft tissue defects reduced from 56.4 cm2 to 42.9 cm2 after NPWT (mean decrease of 24%). In 15 of the 16 cases, coverage with granulation tissue was achieved and followed by a skin graft. A free flap was needed to cover exposed bone and tendon in one case. No major complication occurred that was directly attributable to treatment. In terms of minor complications, two patients suffered scar contracture of grafted skin.ConclusionNPWT was found to facilitate the rapid formation of healthy granulation tissue on open wounds in the foot and ankle region, and thus, to shorten healing time and minimize secondary soft tissue defect coverage procedures.

Double plating of unstable proximal tibial fractures using minimally invasive percutaneous osteosynthesis technique

Background Double plating of proximal tibial fractures with traditional open osteosynthesis gives a stable fixation, but may be complicated by wound healing problems. Minimally invasive methods have been recommended to decrease the wound complication rates. We report the efficacy of double plating of proximal tibial fractures using a minimally invasive percutaneous technique. Patients and methods 23 proximal tibial fractures in 23 patients (mean age 54 (36–78) years) were treated with double plating using a minimally invasive percutaneous technique. Functional and radiographic results were evaluated by a modified Rasmussen scoring system. Results All fractures healed. The average time for fracture healing was 19 (10–32) weeks. 21 patients had excellent or good clinical and radiographic results. 2 patients had a fair clinical result because of associated knee injuries. Complications included 1 case of shortening (1 cm) and 2 cases of mild malalignments (varus less than 10°). There was 1 case of superficial infection that healed after removal of the plate. No deep infections occurred. Interpretation Double plating using minimally invasive percutaneous technique can provide favorable results in the treatment of proximal tibial fractures.

Limb lengthening with a submuscular locking plate

Ten patients, who were unsuitable for limb lengthening over an intramedullary nail, underwent lengthening with a submuscular locking plate. Their mean age at operation was 18.5 years (11 to 40). After fixing a locking plate submuscularly on the proximal segment, an external fixator was applied to lengthen the bone after corticotomy. Lengthening was at 1 mm/day and on reaching the target length, three or four screws were placed in the plate in the distal segment and the external fixator was removed. All patients achieved the pre-operative target length at a mean of 4.0 cm (3.2 to 5.5). The mean duration of external fixation was 61.6 days (45 to 113) and the mean external fixation index was 15.1 days/cm (13.2 to 20.5), which was less than one-third of the mean healing index (48 days/cm (41.3 to 55). There were only minor complications. Lengthening with a submuscular locking plate can successfully permit early removal of the fixator with fewer complications and is a useful alternative in children or when nailing is difficult.

Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow

Many reports have revealed the importance of the sympathetic nervous system (SNS) in the control of the bone marrow environment. However, the specific role of neuropeptide Y (NPY) in this process has not been systematically studied. Here we show that NPY‐deficient mice have significantly reduced hematopoietic stem cell (HSC) numbers and impaired regeneration in bone marrow due to apoptotic destruction of SNS fibers and/or endothelial cells. Furthermore, pharmacological elevation of NPY prevented bone marrow impairments in a mouse model of chemotherapy‐induced SNS injury, while NPY injection into conditional knockout mice lacking the Y1 receptor in macrophages did not relieve bone marrow dysfunction. These results indicate that NPY promotes neuroprotection and restores bone marrow dysfunction from chemotherapy‐induced SNS injury through the Y1 receptor in macrophages. They also reveal a new role of NPY as a regulator of the bone marrow microenvironment and highlight the potential therapeutic value of this neuropeptide.

A biomechanical analysis of locking plate fixation with minimally invasive plate osteosynthesis in a subtrochanteric fracture model.

OBJECTIVE The objective of this study was to establish the relative fixation strengths of a locking plate, a dynamic condylar screw (DCS) plate, and a long proximal femoral nail (PFN). METHODS The study involved three groups of composite large femoral synthetic bones of five specimens per group; plating using a locking compression plate-distal femur (LCP-DF), plating using a DCS plate, and nailing using a long PFN. A gap osteotomy model was used to simulate a comminuted subtrochanteric femur fracture. For each femur, a minimal preload of 100 N was applied before loading to failure. A vertical load was applied at 10 mm/min until femur failure. Load to failure, mode of failure, and displacement at load to failure were documented. RESULTS Fixation strength (load or moment to failure) of LCP-DF (1,330 N; range, 1,217-1,460 N) was 26.6% and was greater in axial loading compared with DCS (1050.5 N; range, 956.4-1194.5 N) and 250% less in axial loading compared with long PFN (3633.1 N; range, 3337.2-4020.4 N; p=0.002). Ultimate displacement in axial loading was similar for LCP-DF (18.4 mm; standard deviation [SD], 1.44), DCS (18.3 mm; SD, 3.25), and long PFN (16.7 mm; SD, 1.82). CONCLUSIONS The LCP-DF construct proved stronger than the DCS in terms of ultimate strength by biomechanical testing of a simulated subtrochanteric femur fracture with comminution. Although the nail construct proved strongest, the biomechanical performance of the locking plate construct may lend credence to the use of a locking plate versus the DCS plate for minimally invasive plate osteosynthesis of subtrochanteric femur fractures, which may be technically difficult to fix using a nail.