Effects of Oxysterols on Chondrogenesis of Human Adipose-derived Stem Cells.

Human adipose-derived stem cells (hADSCs) have been implicated as a high potency source of chondrocytes in cell therapy for cartilage defects. However, appropriate stimulators for the chondrogenesis of hADSCs are needed. Oxysterols have the potential to act as a stimulator. This study aims to investigate the effect of oxysterols on the chondrogenesis of hADSCs. hADSCs were collected from the abdominal subcutaneous tissue samples of patients undergoing caesarean section, and were cultured to passage 5. Mesenchymal stem cell markers were examined by flow cytometry. After the cells were subjected to adipogenic, osteogenic, and chondrogenic induction, the differentiation of each cell lineage was evaluated by RT-PCR and specific staining (Oil red O, Alizarin red S, and Alcian blue, respectively). The cell pellets of hADSCs were cultured in chondrogenic induced media containing 2µM 22(R)-hydroxycholesterol, 22(S)-hydroxycholesterol, or 25-hydroxycholesterol for 4 weeks. At 3 and 4 weeks of culture, the size and wet weight of the pellets were measured. The expressions of chondrogenesis-related genes and glycosaminoglycans production were examined by quantitative real-time PCR and Alcian blue staining. hADSCs were positive for the mesenchymal markers CD75, CD90, and CD105, while being negative for the hematopoietic markers CD31, CD34 and CD45. The multilineage potential of hADSCs was confirmed by the expression of adipogenic-, osteogenic-, and chondrogenic-specific genes, along with specific staining. 22(R)-hydroxycholesterol treatment significantly increased the size and wet weight of the pellet, glycosaminoglycans production, and expression of chondrogenic-related genes compared to the control group and other oxysterols (P<0.05). These results indicate that 22(R)-hydroxycholesterol can be effective as a stimulator for the chondrogenesis of hADSCs.

Factors Associated with the Symptoms of Young Adults with L5 Spondylolysis.

STUDY DESIGN: A retrospective cohort study. PURPOSE: To investigate the factors affecting symptoms in young adults with L5 spondylolysis. OVERVIEW OF LITERATURE: L5 spondylolysis is a common disease. However, not all patients diagnosed with L5 spondylolysis exhibit symptoms. This study examined the factors associated with the symptoms of young adults with L5 spondylolysis. METHODS: The medical records of 70 young adults (mean age, 31.1 years; range, 20-39 years) with L5 spondylolysis treated at the authors' spine center between March 2008 and February 2015 were reviewed systematically. The symptomatic group (n=46) presented with symptoms, such as back pain and/or intermittent lower limb radiating pain, whereas the asymptomatic group (n=24) did not. Age, sex, body mass index (BMI), adjacent disc degeneration, facet degeneration, and measured spino-pelvic parameters (pelvic incidence, sacral slope, pelvic tilt, lumbar lordosis, sacral inclination, and sacral table angle) were investigated with respect to the presence of symptoms. Adjacent disc degeneration was evaluated using T2-weighted sagittal magnetic resonance imaging (MRI, Pfirrmann classification), whereas facet degeneration was evaluated using T2-weighted axial MRI (Grogan classification). RESULTS: Significant differences in the BMI (p =0.032), L4-5 disc degeneration (p =0.030), L5-S1 disc degeneration (p =0.046), L4-5 facet degeneration (p =0.041), and L5-S1 facet degeneration (p =0.027) were observed between the symptomatic and asymptomatic groups. However, multivariate logistic regression analysis revealed that L5-S1 disc degeneration (p =0.033) was the only significant factor. CONCLUSIONS: BMI and adjacent disc and facet degeneration may be associated with the manifestation of disease symptoms in young adults with L5 spondylolysis, and the likelihood of the patient exhibiting symptoms increases with increasing severity of L5-S1 disc degeneration.

Analgesic Efficacy and Safety of Prolonged-Release Oxycodone/Naloxone in Korean Patients with Chronic Pain from Spinal Disorders.

BACKGROUND: A prolonged-release formulation of oxycodone/naloxone has been shown to be effective in European populations for the management of chronic moderate to severe pain. However, no clinical data exist for its use in Korean patients. The objective of this study was to assess efficacy and safety of prolonged-release oxycodone/naloxone in Korean patients for management of chronic moderate-to-severe pain. METHODS: In this multicenter, single-arm, open-label, phase IV study, Korean adults with moderate-to-severe spinal disorder-related pain that was not satisfactorily controlled with weak opioids and nonsteroidal anti-inflammatory drugs received prolonged-release oral oxycodone/naloxone at a starting dose of 10/5 mg/day (maximum 80/40 mg/day) for 8 weeks. Changes in pain intensity and quality of life (QoL) were measured using a numeric rating scale (NRS, 0-10) and the Korean-language EuroQol-five dimensions questionnaire, respectively. RESULTS: Among 209 patients assessed for efficacy, the mean NRS pain score was reduced by 25.9% between baseline and week 8 of treatment (p < 0.0001). There was also a significant improvement in QoL from baseline to week 8 (p < 0.0001). The incidence of adverse drug reactions was 27.7%, the most common being nausea, constipation, and dizziness; 77.9% of these adverse drug reactions had resolved or were resolving at the end of the study. CONCLUSIONS: Prolonged-release oxycodone/naloxone provided significant and clinically relevant reductions in pain intensity and improved QoL in Korean patients with chronic spinal disorders. (ClinicalTrials.gov identifier: NCT01811238).

The Relationship between Superior Disc-Endplate Complex Injury and Correction Loss in Young Adult Patients with Thoracolumbar Stable Burst Fracture.

BACKGROUND: To determine the relationship between superior disc-endplate complex injury and correction loss after surgery in a group of young adult patients with a stable thoracolumbar burst fracture. METHODS: The study group was comprised of young adult patients who had undergone short-segment posterior fixation and bone grafting under the diagnosis of a stable thoracolumbar burst fracture from March 2008 to February 2014. Follow-up was available for more than 1 year. Before surgery, magnetic resonance imaging was performed to determine injury to the anterior longitudinal ligament, posterior longitudinal ligament, and superior and inferior intervertebral discs and endplates. Correction loss was evaluated by the Cobb angle, intervertebral disc height, upper intervertebral disc angle, vertebral wedge angle, and vertebral body height. RESULTS: No significant relation was noted between correction loss and an injury to the anterior longitudinal ligament, posterior longitudinal ligament, inferior intervertebral disc/endplate, and fracture site, whereas an injury to the superior endplate alone and superior disc-endplate complex showed a significant association. Specifically, a superior intervertebral disc-endplate complex injury showed statistically significant relation to postoperative changes in Cobb angle (p = 0.026) and vertebral wedge angle (p = 0.047). CONCLUSIONS: A superior intervertebral disc-endplate complex injury may have an influence on the prognosis after short-segment fixation in young adult patients with a stable thoracolumbar burst fracture.

Efficacy and Safety of Transdermal Buprenorphine versus Oral Tramadol/Acetaminophen in Patients with Persistent Postoperative Pain after Spinal Surgery.

PURPOSE: Control of persistent pain following spinal surgery is an unmet clinical need. This study compared the efficacy and safety of buprenorphine transdermal system (BTDS) to oral tramadol/acetaminophen (TA) in Korean patients with persistent, moderate pain following spinal surgery. METHODS: Open-label, interventional, randomized multicenter study. Adults with persistent postoperative pain (Numeric Rating Scale [NRS] ≥ 4 at 14-90 days postsurgery) were enrolled. Patients received once-weekly BTDS (n = 47; 5 µg/h titrated to 20 µg/h) or twice-daily TA (n = 40; tramadol 37.5 mg/acetaminophen 325 mg, one tablet titrated to 4 tablets) for 6 weeks. The study compared pain reduction with BTDS versus TA at week 6. Quality of life (QoL), treatment satisfaction, medication compliance, and adverse events (AEs) were assessed. FINDINGS: At week 6, both groups reported significant pain reduction (mean NRS change: BTDS -2.02; TA -2.76, both P < 0.0001) and improved QoL (mean EQ-5D index change: BTDS 0.10; TA 0.19, both P < 0.05). The BTDS group achieved better medication compliance (97.8% versus 91.0%). Incidence of AEs (26.1% versus 20.0%) and adverse drug reactions (20.3% versus 16.9%) were comparable between groups. IMPLICATIONS: For patients with persistent pain following spinal surgery, BTDS is an alternative to TA for reducing pain and supports medication compliance. This trial is registered with Clinicaltrials.gov: NCT01983111.

Radiologic and Clinical Courses of Degenerative Lumbar Scoliosis (10°-25°) after a Short-Segment Fusion.

STUDY DESIGN: Retrospective study. PURPOSE: We report the surgical outcomes of small degenerative lumbar scoliosis (DLS) patients treated by a short-segment fusion and followed for a minimum of 5 years. OVERVIEW OF LITERATURE: Several surgical options are available for the treatment of DLS, such as decompression only, decompression plus a short-segment fusion, or decompression with a long segment fusion. Few studies have evaluated the results of a short-segment fusion in patients with DLS over time. METHODS: Seventy small DLS patients (Cobb's angle, 10°-25°) with a minimum follow-up of 5 years were treated with a short-segment fusion between March 2004 and February 2010. The mean patient age was 71 (male:female=16:54), with a follow-up of 6.5 years (range, 5.0-11.6). The Cobb's angle, 1 and 2 segment coronal upper intervertebral angle, 1 and 2 segment sagittal upper intervertebral angle, the lumbar lordosis angle, and the C7 plumb lines (coronal and sagittal) were evaluated using simple radiographs, and visual analog scale (VAS), back pain was assessed preoperatively, immediately after surgery, and at 3, 6, and 12 months and 3 and 5 years after surgery. To identify factors influencing the radiologic progression, age, number of fusion segments, vertebral levels of fusion, body mass index, lowest instrumented vertebra (L5 or S1), bone mineral density (>-2.5, ≤-2.5), and the presence of an interbody fusion were analyzed. RESULTS: The Cobb's angle and 1 segment coronal upper intervertebral angle showed more progression during follow up, particularly at 6 and 12 months after surgery. Clinical outcomes and radiological results were found to be significantly associated (p=0.041). No statistically significant association was found between other factors affecting radiologic progression from postoperative 6 months to 1 year. CONCLUSIONS: Radiologic variables (the Cobb's angle and coronal upper intervertebral angle-1) should be carefully considered and clinical caution exercised from 6 to 12 months after short-segment fusion in small DLS (10°-25°).

Tumor associated macrophages provide the survival resistance of tumor cells to hypoxic microenvironmental condition through IL-6 receptor-mediated signals.

Hypoxia and infiltration of tumor-associated macrophages (TAM) are intrinsic features of the tumor microenvironment. Tumor cells that remain viable in hypoxic conditions often possess an increased survival potential and tend to grow aggressively. TAM also respond to a variety of signals in the hypoxic tumor microenvironment and express a more M2-like phenotype. In this study, the established mouse tumor tissues showed a dense infiltration of CD206+ macrophages at the junctions between the normoxic and hypoxic regions and an increased IL-6 receptor (IL-6R) expression of tumor cells in the areas of CD206+ TAM accumulation, which indicates a role of M2 phenotype TAM in survival adaptation of tumor cells preparing for an impending hypoxic injury before changes in oxygen availability. Cocultured mouse FM3A or human MCF-7 tumor cells with tumor infiltrating macrophages isolated from mouse tumor tissues and M2-polarized macrophages generated from human THP-1 cells, respectively, showed significantly decreased rate of cell death in cultures exposed to hypoxia. The acquisition of survival resistance was attributed to increased IL-6 production by M2 TAM and increased expression of IL-6R in tumor cells in the coculture system. MCF-7 cells cocultured with M2 TAM showed activated JAK1/STAT3 and Raf/MEK/JNK pathways contributing to tyrosine and serine phophorylation of STAT3, respectively. However, only tyrosine phosphorylated STAT3 was detected in the nucleus, which induced upregulation of Bcl-2 and downregulation of Bax and Bak. Finally, knockdown of IL-6R by small interfering RNA significantly counteracted coculture-induced signals and completely abolished the survival resistance to hypoxic injury. Thus, we present evidence for the role of M2 phenotype TAM in IL-6 receptor-mediated signals, particularly tyrosine phosphorylation of STAT3, responsible for the prosurvival adaptation of tumor cells to hypoxia.

A Nationwide Retrospective Study of Opioid Management Patterns in 2,468 Patients with Spinal Pain in Korea.

STUDY DESIGN: Retrospective patient data collection and investigator survey. PURPOSE: To investigate patterns of opioid treatment for pain caused by spinal disorders in Korea. OVERVIEW OF LITERATURE: Opioid analgesic prescription and adequacy of consumption measures in Korea have markedly increased in the past decade, suggesting changing patterns in pain management practice; however, there is lack of integrated data specific to Korean population. METHODS: Patient data were collected from medical records at 34 university hospitals in Korea. Outpatients receiving opioids for pain caused by spinal disorders were included in the study. Treatment patterns, including opioid types, doses, treatment duration, outcomes, and adverse drug reactions (ADRs), were evaluated. Investigators were interviewed on their perceptions of opioid use for spinal disorders. RESULTS: Among 2,468 analyzed cases, spinal stenosis (42.8%) was the most common presentation, followed by disc herniation (24.2%) and vertebral fracture (17.5%). In addition, a greater proportion of patients experienced severe pain (73.9%) rather than moderate (19.9%) or mild (0.7%) pain. Oxycodone (51.9%) and fentanyl (50.8%) were the most frequently prescribed opioids; most patients were prescribed relatively low doses. The median duration of opioid treatment was 84 days. Pain relief was superior in patients with longer treatment duration (≥2 months) or with nociceptive pain than in those with shorter treatment duration or with neuropathic or mixed-type pain. ADRs were observed in 8.6% of cases. According to the investigators' survey, "excellent analgesic effect" was a perceived advantage of opioids, while safety concerns were a disadvantage. CONCLUSIONS: Opioid usage patterns in patients with spinal disorders are in alignment with international guidelines for spinal pain management. Future prospective studies may address the suitability of opioids for spinal pain treatment by using appropriate objective measurement tools.

Clinical Usefulness of Long-term Application of Fentanyl Matrix in Chronic Non-Cancer Pain: Improvement of Pain and Physical and Emotional Functions.

BACKGROUND: Opioids are recently recommended for those who do not gain adequate pain relief from the use of acetaminophen or nonsteroidal anti-inflammatory drugs. Medical opioids are administered in various routes, and transdermal opioid products that can make up for the weaknesses of the oral or intravenous products have been developed. This study is to evaluate the clinical usefulness of fentanyl matrix in terms of the long-term improvement in pain and physical and mental functions. METHODS: This was a multicenter, open, prospective, observational study that was conducted in 54 institutions in Korea. Patients with non-cancerous chronic pain completed questionnaires, and investigators also completed questionnaires. A total of 1,355 subjects participated in this study, and 639 subjects completed the study. Subjects received transdermal fentanyl matrix (12 µg/hr, 25 µg/hr, or 50 µg/hr depending on the patient's response and demand). Subjects visited at 29 ± 7 days, 85 ± 14 days, and 169 ± 14 days after administration, respectively, to receive drug titration and fill out the questionnaires. The results were analyzed using the intention-to-treat (ITT) analysis, full analysis set (FAS), and per-protocol (PP) analysis. The FAS analysis included only 451 participants; the PP analysis, 160 participants; and the ITT analysis, 1,355 participants. RESULTS: The intensity of pain measured by the Numeric Rating Scale decreased from 7.07 ± 1.78 to 4.93 ± 2.42. The physical assessment score and mental assessment score of the Short-Form Health Survey 12 improved from 28.94 ± 7.23 to 35.90 ± 10.25 and from 35.80 ± 11.76 to 42.52 ± 10.58, respectively. These differences were significant, and all the other indicators also showed improvement. Adverse events with an incidence of ≥ 1% were nausea, dizziness, vomiting, and pruritus. CONCLUSIONS: The long-term administration of fentanyl matrix in patients with non-cancerous pain can reduce the intensity of pain and significantly improves activities of daily living and physical and mental capabilities.

Changes in Tip-Apex Distance by Position and Film Distance Measured by Picture Archiving and Communication System (PACS).

PURPOSE: The tip-apex distance (TAD) is used to predict the clinical outcome of intertrochanteric fracture fixation. We aimed to measure the changes in TAD by position and film distance using Picture Archiving and Communication System (PACS). MATERIALS AND METHODS: We used a femur replica with a 10° femoral neck anteversion and a 130° neck shaft angle. Proximal femoral nail antirotation nail and a helical blade were inserted into the replica. Radiographs were taken at the neutral position and after applying 10°, 20°, 30°, 40° internal/external rotation, 10° abduction, and 10° and 40° adduction to the mechanical axis. Radiographs were taken at the replica-film distance of 10 cm and 20 cm under the same conditions, mimicking the differences in Focus-film distance (FFD), which reflect the patient's contour in clinical settings. A radiologist and an orthopedic surgeon measured the TAD twice using PACS. The average error was 2 mm (4.5%) and the standard error was ±3.04. TADs in the neutral position constituted the standard values to measure the relative errors. RESULTS: TADs increased with an increase in the external rotation and abduction of the replica. TADs decreased with an increase in the internal rotation and adduction of the replica. For comparable measurements, relative errors were higher at FFDs of 20 cm compared to FFDs of 10 cm. CONCLUSION: Since the femur is internally rotated and adducted for reduction, orthopedic surgeons would assess the lag screw to be closer to the apex of femur on intraoperative radiographs. To have a correct measurement of the TAD after fixation of intertrochanteric fractures, radiographs should be taken in neutral position and measurement errors should be considered based on the patient's size.

Interferon gamma induced by resveratrol analog, HS-1793, reverses the properties of tumor associated macrophages.

Macrophages are capable of both inhibiting and promoting the growth and spread of cancers, depending on their activation state. Tumor-associated macrophages (TAM) are a kind of alternatively activated M2 macrophage, which may contribute to tumor progression. Following our previous study to evaluate the anti-tumor effect of a synthetic resveratrol analog HS-1793, the current study demonstrated that HS-1793 treatment significantly increased IFN-γ secreting cells in splenocytes and decreased CD206+ macrophage infiltration compared to CD68+ cells in the tumor site with a higher expression of IFN-γ. As these results suggested that IFN-γ increased locally at the tumor sites could modulate the status of TAM, we designed an in vitro model to study macrophage morphology and functions in relation to the tumor microenvironment. Human monocytic cell line THP-1 cells stimulated with phorbol-12-myristate-13-acetate (PMA) differentiated to macrophages with M2-like phenotypes. TAM-like properties of CD206(high), CD204(high), IL-10(high), TGF-ß(high), IL-6(low), IL-12(low), VEGF(high), and MMP-9(high) and promotion of tumor cell invasion were more pronounced in M-2-polarized THP-1 macrophages generated by differentiating THP-1 cells with PMA and subsequently polarizing them with Th2 cytokines (IL-4/IL-13). Upon IFN-γ exposure, THP-1-derived TAM changed their phenotypes to the M-1-like morphology and intracellular granular pattern with an expression of an increased level of proinflammatory and immunostimulatory cytokines and a reduced level of immunosuppressive and tumor progressive mediators. These results explain the underlying mechanism of the anti-tumor activity of HS-1793. The elevated level of IFN-γ production after HS-1793 treatment evoked reprogramming of M-2 phenotype TAM, which efficiently countered the immunosuppressive and tumor progressive influences of TAM.

How does chronic back pain influence quality of life in koreans: a cross-sectional study.

STUDY DESIGN: A cross-sectional study. PURPOSE: To explore the impact of chronic low back pain (CLBP) on individuals' quality of life; to understand current treatment practices and level of satisfaction with treatment in patients with CLBP. OVERVIEW OF LITERATURE: Assessing subjective, patient-reported outcomes such as quality of life is essential to health care research. METHODS: Influences of the CLBP were analyzed via a questionnaire, which contained the character of CLBP, effect of pain management, Korean version Oswestry Disability Index (K-ODI) and Korean version of 12-item Short Form Health Survey (SF-12v2). RESULTS: Of 3,121 subjects who responded, 67.3% had moderate to severe pain; 43.5% presented prolonged CLBP of more than two years; and 32.4% had suffered from sleep disturbance due to pain. 22.8% of the patients were not satisfied with current pain management. The mean K-ODI score was 37.63; and it was positively correlated with the mean pain intensity (r=0.6, p<0.001). The SF-12v2 result was negatively correlated with mean pain intensity (PCS: r=-0.5, p<0.001; MCS: r=-0.4, p<0.001) and also negatively correlated with the K-ODI score (PCS: r=-0.75, p<0.001; MCS: r=-0.5, p<0.001). The conformity between patients and doctors in pain assessment was fair (κ=0.2463). CONCLUSIONS: CLBP negatively affects quality of life. Of total 22.8% of the patients were not satisfied with current pain management. Such needs to be taken more seriously by doctors for improvement of satisfaction and quality of life in patients with CLBP.

Comparison of pyogenic spondylitis and tuberculous spondylitis.

Pyogenic spondylitis and tuberculous spondylitis are common causes of spinal infection. It is difficult to differentiate tuberculous spondylitis and pyogenic spondylitis clinically and radiologically. Recently magnetic resonance imaging has been reported to be beneficial for early diagnosis and differential diagnosis of the spondylitis, and is being used extensively for diagnosis. However, the diagnosis must be considered in combination with corresponding changes in clinical manifestations, radiological findings, blood and tissue cultures and histopathological findings. Conservative treatments, including antimicrobial medications, are started initially. Surgical treatments, which include anterior or posterior approach, single-stage or two-stage surgery, with or without instrumentation, may be performed as indicated.

Cytoprotective role of autophagy during paclitaxel-induced apoptosis in Saos-2 osteosarcoma cells.

Osteosarcoma (OS) is the most common primary malignant bone cancer in children and adolescents. Although paclitaxel (PCX) has been considered one of the most important cancer chemotherapeutic drugs, the current protocols for OS treatment do not incorporate this agent. Therefore, the purpose of this study was to evaluate the induction of cell death in OS cells after exposure to PCX, to identify the cell death mechanism(s) activated by PCX and to investigate whether autophagy is associated with PCX-induced apoptosis. The results of the present study confirmed that exposure to low PCX concentrations can induce apoptotic cell death in Saos-2 cells; furthermore, caspase-3 activation, PARP degradation and XIAP downregulation were observed in combination with PCX-induced apoptosis. The potential involvement of mitochondrial events (intrinsic apoptotic pathway) in PCX-induced apoptosis in OS cells was verified by the alteration (depolarization) of mitochondrial membrane potential. In addition, pretreatment with 3-methyladenine (3-MA), a specific inhibitor of autophagy, significantly increased PCX-induced apoptotic cell death in Saos-2 cells. The augmentation of PCX-induced apoptosis by 3-MA was accompanied by increase in the cytochrome c release from the mitochondria, caspase-3 activity and XIAP downregulation, which suggests that inhibiting autophagy further stimulates the PCX-induced mitochondrion-related (intrinsic) apoptotic pathway by provoking caspase-3 activation. Thus, autophagy observed during PCX-induced apoptosis in Saos-2 OS cells represents the role of cytoprotection in cellular homeostatic processes. In conclusion, the results of this study revealed that PCX exposure effectively induces OS cell death by apoptosis associated with the mitochondrial-mediated caspase-dependent pathway. PCX can increase autophagic activity and suppressing autophagy enhances PCX-induced apoptosis in OS cells. Therefore, it is suggested that combination treatment involving low-dose PCX therapy and autophagy inhibitor therapy could be an effective and potent strategy for improved chemotherapy for OS in the near future.

Therapeutic effects of mesenchymal stem cells and hyaluronic Acid injection on osteochondral defects in rabbits' knees.

PURPOSE: To evaluate the treatment results of intraarticular injection according to the frequency of hyaluronic acid with mesenchymal stem cells on the osteochondral defect of rabbits' medial femoral condyles. MATERIALS AND METHODS: A 5 mm diameter and 4 mm depth osteochondral defect was made on the medial femoral condyles of 18 rabbits, divided into six groups. One week after osteochondral defect, group B was injected intraarticularly with hyaluronic acid (HA), group C with mesenchymal stem cells (MSCs), and group D, E and F with both HA and MSCs. Group E and F received second HA injection a week after. Further, group F received third HA injection in the third week. RESULTS: In a macroscopic evaluation, groups B (6; range, 5-8), C (6; range, 6-7), D (7; range, 6-7), E (6.5; range, 6-8) and F (7.5; range, 6-8) showed statistically significant improvements in osteochondral defect healing, compared with that of group A (4; range, 3-5) (p=0.002). In histological evaluation, groups B (11.5; range, 11-13), C (13; range, 12-18), D (16; range, 13-18), E (17.5; range, 13-20), and F (19.5; range, 12-22) showed statistically significant differences in osteochondral defect healing, compared with group A (8; range, 6-9) (p=0.006). CONCLUSIONS: The intraarticular injections of MSCs or HA can play an effective role during the healing osteochondral defects in rabbits.

Bloodless cancer treatment results of patients who do not want blood transfusion: single center experience of 77 cases.

PURPOSE: Certain patients may be unwilling to accept blood products for religious reasons. In this study, we have assessed the clinical cancer treatment outcomes of Jehovah's Witnesses (JW) cancer patients in order to identify the risks associated with their treatment, as well as their transfusion needs. METHODS: We analyzed 77 cases of histologically confirmed cancer patients (JW) from January 2001 to April 2008. RESULTS: The median age of the patients was 59 years (range, 8-83 years). The most common primary site was the stomach (20.8%), followed by the breast (14.3%), and colorectal region (11.7%). Operations were performed on 44 patients (89.8%). Changes in complete blood count profiles after operation were detected in the patients' hemoglobin (mean +/- SD; 12.7 +/- 2.1 g/dL to 10.6 +/- 2.3 g/dL, P < 0.001). Twenty-six patients received adjuvant chemotherapy. Among these, 21 (80.8%) completed their planned schedule. One hundred twenty-seven cycles of palliative intravenous chemotherapy were administered to 19 patients. Granulocyte-colony stimulating factor and erythropoietin were used in 45 and 20 cycles of treatment, respectively. Grade > or =III thrombocytopenia and anemia were noted in 3.9% and 2.4% of the patients. Three- and 5-year survival rates were 80% and 70%, respectively. The most frequent cause of death was disease progression rather than bleeding. CONCLUSIONS: Bloodless cancer operation and chemotherapy were not accompanied by serious complications. A few cases of palliative chemotherapy also required transfusions. A prospective cohort study group will need to be used to determine precisely the safety of bloodless cancer treatment and the efficacy of transfusion alternatives.

Cell type-specific STAT3 activation by gp130-related cytokines in the peripheral nerves.

Nerve injury-induced activation of signal transducer and activator of transcription 3 (STAT3) in sensory neurons and Schwann cells has been implicated in peripheral nerve regeneration. In this study, we investigated the role of gp130-related cytokines including interleukin-6 (IL-6), ciliary neurotrophic factor (CNTF), and leukemia inhibitory factor (LIF) in STAT3 activation in dorsal root ganglion neurons, Schwann cells, and endoneurial fibroblasts. We found that IL-6, but not CNTF or LIF, activated STAT3 in Schwann cells. However, CNTF and LIF, but not IL-6, activated STAT3 in dorsal root ganglion neurons. Furthermore, LIF was the primary activator of STAT3 in endoneurial fibroblasts. These findings indicate that gp130 cytokines may have cell type-specific roles in peripheral nerve regeneration.

Interleukin-6 induces proinflammatory signaling in Schwann cells: a high-throughput analysis.

Interleukin-6 plays an important role in peripheral nerve regeneration. We recently reported that IL-6 targets Schwann cells in the peripheral nerve for its function. In this study, we analyzed genes whose expression is regulated by IL-6 in a cell line derived from Schwann cells, the peripheral glia, using the Illumina gene microarray. At measurements 3 and 12h after IL-6 treatment, 35 genes were found to be upregulated by IL-6. Most upregulated genes were proinflammatory genes that are known to be induced in inflammatory conditions. Interestingly, the expression of immunoproteasome subunits was upregulated by IL-6 in Schwann cells. Treatment with forskolin, an agent that mimics axonal signaling, suppressed the expression of IL-6-inducible genes. Finally, we found for the first time that sciatic nerve injury induced immunoproteasome expression in vivo. These findings indicate that IL-6 is involved in peripheral nerve regeneration by regulating proinflammatory signaling in Schwann cells.

Effects of human amniotic membrane grafts combined with marrow mesenchymal stem cells on healing of full-thickness skin defects in rabbits.

We have investigated the wound-healing effects of mesenchymal stem cells (MSCs) in combination with human amniotic membrane (HAM) when grafted into full-thickness skin defects of rabbits. Five defects in each of four groups were respectively treated with HAM loaded with autologous MSCs (group A), HAM loaded with allologous MSCs (group B), HAM with injected autologous MSCs (group C), and HAM with injected allologous MSCs (group D). The size of the wounds was calculated for each group at 7, 12, and 15 days after grafting. The wounds were subsequently harvested at 25 days after grafting. Sections stained with hematoxylin and eosin were used to determine the quality of wound healing, as based on the characteristics and amount of granulated tissue in the epidermal and dermal layers. Groups A and B showed the most pronounced effect on wound closure, with statistically significant improvement in wound healing being seen on post-operative days 7, 12, and 15. Although a slight trend toward improved wound healing was seen in group A compared with group B, no statistically significant difference was found at any time point between the two groups. Histological examination of healed wounds from groups A and B showed a thin epidermis with mature differentiation and collagen bundle deposition plus recovered skin appendages in the dermal layer. In contrast, groups C and D showed thickened epidermis with immature epithelial cells and increased fibroblast proliferation with only partially recovered skin appendages in the dermal layer. Thus, the graft of HAM loaded with MSCs played an effective role during the healing of skin defects in rabbits, with no significant difference being observed in wound healing between autologous and allologous MSC transplantation.

Treatment outcome of cervical tear drop fracture.

STUDY DESIGN: This is a retrospective study. PURPOSE: We wanted to evaluate the clinical results of surgical and conservative treatment for cervical tear drop fracture. OVERVIEW OF LITERATURE: The tear drop fracture of the lower cervical spine is generally associated with a high incidence of neurological deficits and surgery is needed to treat this injury. Tear drop fracture of C2 is usually a stable fracture that is amendable to conservative treatment. METHODS: We reviewed the outcomes of 25 patients. Cervical tear drop fracture was classified as the extension and flexion types according to the mechanism of injury. The neurologic symptoms were evaluated by the Frankel classification system, and the loss of lordosis and disc height, and the duration of bony union were analyzed. RESULTS: Twenty one patients had the flexion type injury and 4 patients had the extension type injury. All the patients with the flexion type were treated by anterior decompression and plate stabilization. All the patients with the extension type were treated conservatively. Ten patients with the flexion type had neurologic deficits. The nerve root injuries recovered fully and the incomplete injuries had an average 1.5 grade recovery. Radiologically, the extension type fracture showed bony union at an average of 12.8 weeks. For the patients with the flexion type fracture, the loss of lordosis was 2.6 degrees and the loss of disc height was 2.1 mm. The period of bony union in 20 cases was 13.0 weeks. CONCLUSIONS: Anterior plate stabilization was an effective treatment for the flexion type tear drop fracture. Conservative treatment is thought to be one of the good clinical methods for treating the extension type tear drop fracture.