Balloon-expandable cobalt chromium stent versus self-expandable nitinol stent for the Atherosclerotic Iliac Arterial Disease (SENS-ILIAC Trial) Trial: a randomized controlled trial.

Iliac artery angioplasty with stenting is an effective alternative treatment modality for aortoiliac occlusive diseases. Few randomized controlled trials have compared the efficacy and safety between self-expandable stent (SES) and balloon-expandable stent (BES) in atherosclerotic iliac artery disease. In this randomized, multicenter study, patients with common or external iliac artery occlusive disease were randomly assigned in a 1:1 ratio to either BES or SES. The primary end point was the 1-year clinical patency, defined as freedom from any surgical or percutaneous intervention due to restenosis of the target lesion after the index procedure. The secondary end point was a composite event from major adverse clinical events at 1 year. A total of 201 patients were enrolled from 17 major cardiovascular intervention centers in South Korea. The mean age of the enrolled patients was 66.8 ± 8.5 years and 86.2% of the participants were male. The frequency of critical limb ischemia was 15.4%, and the most common target lesion was in the common iliac artery (75.1%). As the primary end point, the 1-year clinical patency as primary end point was 99% in the BES group and 99% in the SES group (p > 0.99). The rate of repeat revascularization at 1 year was 7.8% in the BES group and 7.0% in the SES group (p = 0.985; confidence interval, 1.011 [0.341-2.995]). In our randomized study, the treatment of iliac artery occlusive disease with self-expandable versus balloon-expandable stent was comparable in 12-month clinical outcomes without differences in the procedural success or geographic miss rate regardless of the deployment method in the distal aortoiliac occlusive lesion (ClinicalTrials.gov, NCT01834495).

Full endoscopic surgery for calcium pyrophosphate deposition disease (CPPD) in the cervical ligamentum flavum: report of two cervical myelopathy cases.

Calcium pyrophosphate deposition disease (CPPD), known as pseudogout, is characterized by the accumulation of calcium pyrophosphate crystals in musculoskeletal structures, primarily joints. While CPPD commonly affects various joints, involvement in the cervical spine leading to myelopathy is rare. Surgical intervention becomes necessary when conservative measures fail, but reports on full endoscopic surgeries are extremely rare. We present two successful cases where full endoscopic systems were used for CPPD removal in the cervical spine. The surgical technique involved a full endoscopic approach, adapting the previously reported technique for unilateral laminotomy bilateral decompression. Full-endoscopic removal of cervical CPPD inducing myelopathy were successfully removed with good clinical and radiologic outcomes. The scarcity of endoscopic cases for cervical ligamentum flavum CPPD is attributed to the condition's rarity. However, our successful cases advocate for endoscopic surgery as a potential primary treatment option for CPPD-induced cervical myelopathy, especially in elderly patients or those with previous cervical operation histories. This experience encourages the consideration of endoscopic surgery for managing cervical ligamentum flavum CPPD as a viable alternative.

Phototherapy suppresses inflammation in human nucleus pulposus cells for intervertebral disc degeneration.

The etiology of intervertebral disc (IVD) degeneration accompanied by low back pain (LBP) is largely unknown, and there are no curative therapies. Painful IVD degeneration is associated with infiltrated macrophage-mediated inflammatory response of human nucleus pulposus (NP) cells. The present study aimed to address the hypothesis that pro-inflammatory cytokines derived from macrophages lead to the altered molecular phenotype of human NP cells and to investigate the effects of phototherapy (630, 525, 465 nm with 16, 32, 64 J/cm2) on pain-related cytokine interleukin (IL)-6 and chemokine IL-8 under inflammatory conditions in human NP cells. Human NP cells were treated with soluble factors derived from macrophages in an inflammatory microenvironment, similar to that found in degenerative IVD. Human NP cells were also treated with phototherapy (630, 525, 465 nm with 16, 32, 64 J/cm2), and their cytokine and chemokine levels were detected. The soluble factors caused modulated expression of IL-6, IL-8, and matrix metalloproteinases (MMPs) at the gene and protein levels, causing a shift toward matrix catabolism through the expression of MMPs and increased pain-related factors via preferential activation of the nuclear factor-kappa B (NF-κB) p50 protein. Importantly, phototherapy attenuated the protein and gene expression of pain-related factor IL-6 at all doses and wavelengths. Interestingly, phototherapy also modulated the protein and gene expression of IL-8, which is responsible for the anabolic response, at a wavelength of 465 nm at all doses, in human NP cells. These findings suggested that phototherapy, at an optimal dose and wavelength, might be a useful therapeutic tool to treat IVD degeneration.

Photobiomodulation on human annulus fibrosus cells during the intervertebral disk degeneration: extracellular matrix-modifying enzymes.

Destruction of extracellular matrix (ECM) leads to degeneration of the intervertebral disk (IVD), which is a major contributor to many spine disorders. IVD degeneration is induced by pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß), which are secreted by immune cells, including macrophages and neutrophils. The cytokines modulate ECM-modifying enzymes such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human annulus fibrosus (AF) cells. The resulting imbalance in catabolic and anabolic enzymes can cause generalized back, neck, and low back pain (LBP). Photobiomodulation (PBM) is known to regulate inflammatory responses and wound healing. The aim of this study was to mimic the degenerative IVD microenvironment, and to investigate the effect of a variety of PBM conditions (wavelength: 635, 525, and 470 nm; energy density: 16, 32, and 64 J/cm(2)) on the production of ECM-modifying-enzymes by AF cells under degenerative conditions induced by macrophage-conditioned medium (MCM), which contains pro-inflammatory cytokines such as TNF-α and IL-ß secreted by macrophage during the development of intervertebral disk inflammation. We showed that the MCM-stimulated AF cells express imbalanced ratios of TIMPs (TIMP-1 and TIMP-2) and MMPs (MMP-1 and MMP-3). PBM selectively modulated the production of ECM-modifying enzymes in AF cells. These results suggest that PBM can be a therapeutic tool for degenerative IVD disorders.

Lumbar fusion surgery in the era of an aging society: analysis of a nationwide population cohort with minimum 8-year follow-up.

BACKGROUND CONTEXT: Fusions for lumbar spine diseases are widely performed and have a growing incidence, especially in elderly population. PURPOSE: The goal of this study was to assess national trends of lumbar spinal fusions and examine the risk for re-operations after a lumbar fusion with a focus on 'epidemiologic transition' relating to age. STUDY DESIGN/SETTING: The prospectively collected Korean Health Insurance Review and Assessment Service (HIRA) nationwide cohort database was retrospectively reviewed. PATIENT SAMPLE: The total 278,815 patients who underwent lumbar spinal fusions for degenerative spine diseases between 2010 and 2018 were reviewed and used to assess trends in operative incidence. The 37,050 patients who underwent lumbar fusions between 1/2010 and 12/2011 were enrolled to determine 8-year reoperation rates. OUTCOME MEASURES: The overall number of lumbar spinal fusions were analyzed for the national annual trend. Demographic data, reoperation rates, and confounding clinical factors were evaluated. METHODS: The overall number of lumbar spinal fusions was analyzed to determine the national annual trend of operative incidence. For the reoperation rate analysis, the primary outcome measured was the cumulative incidence of revision operations within a minimum 8-year follow-up period. Additional outcomes included comparative analyses of the reoperation rate with respect to age, sex, or other underlying comorbidities. RESULTS: Over time, elderly patients comprised a larger portion of the cohort (2010:24.2%; 2018:37.6%), while operations in younger patients decreased over time (2010:40.3%; 2018:27.0%). In the cohort of patients with a minimum 8-year follow-up (n=37,050), rates of reoperation peaked in patients aged 60-69 years (17.6 per 1000 person-years [HR 2.20 compared to <40years]) and decreased for more elderly patients (14.3 per 1000 person-years [HR 1.80 compared to <40years]). Age was the most significant risk factor for reoperation. Osteoporosis was also a risk factor for reoperation in post-menopausal females. CONCLUSIONS: Increasing incidence of lumbar fusions in elderly patients was seen however the risk of reoperation decreased in patients aged 70 or more. Lumbar fusion for elderly patients should not be hesitated in the decision-making process because of concerns about reoperation.

A quantitative analysis of surgical smoke-derived particulate matter and formaldehyde exposure during spine surgery: a possible occupational hazard.

OBJECTIVE: Since its introduction, electrocautery has served as a valuable surgical tool, enabling precise tissue cutting and effective hemostasis in spine surgery. While there have been numerous efforts to elucidate the possible hazardous effects of surgical smoke in various surgical fields, there has been very little discussion in the context of spine surgery. The objective of this study was to measure and conduct a quantitative analysis of the particulate matter (PM) of different sizes and of formaldehyde (HCHO) generated by smoke during spine surgeries. METHODS: This study included a consecutive series of patients who underwent 1- or 2-level lumbar spinal fusion surgery between June and November 2021. Particle counts were measured using a particle counter, specifically focusing on six different sizes of PM (0.3, 0.5, 1, 2.5, 5, and 10 µm). Additionally, measurements were taken for HCHO in parts per million (ppm). Monopolar cautery was used in the surgical setting. Systematic measurements were conducted at specific time points during the surgical procedures to assess the levels of PM and HCHO. Furthermore, the efficacy of surgical smoke suction was evaluated by comparing the PM levels with and without adjacent placement of suction. RESULTS: This study involved 35 patients, with measurements of both PM and HCHO taken in 27 cases. The remaining 8 cases had measurements only for PM. In this study, statistically significant quantitative changes in various PM sizes were observed when electrocautery was used during spine surgery (12.3 ± 1.7 vs 1975.7 ± 422.8, 3.4 ± 0.5 vs 250.1 ± 45.7, and 1.9 ± 0.2 vs 78.1 ± 13.3, respectively, for 2.5-, 5-, and 10-µm PM; p < 0.05). The level of HCHO was also significantly higher (0.085 ± 0.006 vs 0.131 ± 0.014 ppm, p < 0.05) with electrocautery use. Utilization of adjacent suction of surgical smoke during electrocautery demonstrated a statistically significant reduction in PM levels. CONCLUSIONS: The findings of this study highlight the potential surgical smoke-related hazards that spine surgeons may be exposed to in the operating room. Implementing simple interventions, such as utilizing nearby suction, can effectively minimize the amount of toxic surgical smoke and mitigate these risks.

Postoperative survival after lumbar instrumented surgery for metastatic spinal tumors: a nationwide population-based cohort analysis.

BACKGROUND: It is difficult to predict the expected survival after lumbar instrumented surgery for metastases owing to the difference among different cancer origins and the relatively short survival after surgery. AIMS: The aim of this study is to analyze the postoperative survival period of lumbar spinal metastasis patients who underwent lumbar instrumented surgery. METHODS: Data were collected from the Korean National Health Insurance Review and Assessment Service database. Patients who underwent lumbar spinal surgery with instrumentation between January 2011 and December 2015 for metastatic lumbar diseases were reviewed. The mean postoperative survival period of patients with metastatic lumbar cancer according to each primary cancer type was evaluated. RESULTS: A total of 628 patients were enrolled and categorized according to primary cancer type. The overall median survival rate was 1.11±1.30 years. The three most prevalent primary cancer groups were lung, hepatobiliary, and colorectal cancers, presenting relatively short postoperative survival rates (0.93±1.25, 0.74±0.75 and 0.74±0.88 years, respectively). The best postoperative survival period was observed in breast cancer (2.23±1.83 years), while urinary tract cancer showed the shortest postoperative survival period (0.59±0.69 years). CONCLUSION: The postoperative survival period of patients with lumbar metastatic spinal tumors according to different primary cancers after instrumented fusion was ˃1 year overall, with differences according to different primary origins. This result may provide information regarding the expected postoperative survival after instrumented surgery for lumbar spinal metastases.

Cigarette smoking is paradoxically associated with low mortality risk after acute myocardial infarction.

BACKGROUND: Cigarette smoking has been shown to be associated with a decreased risk of death after acute myocardial infarction (AMI), which is also known as the "smokers' paradox." This study aimed to investigate the relationship between smoking and all-cause mortality after AMI. METHODS: We extracted the data of patients who were hospitalized for AMI between November 2005 and September 2010 from nationwide multicenter prospective registries in Korea. RESULTS: Among a total of 29,199 patients with AMI, 10,251 (42.3%) were current smokers, and 14,006 (57.7%) were nonsmokers. Current smokers were younger, more likely to be male, and had lower frequencies of hypertension, diabetes mellitus, dyslipidemia, and previous history of ischemic heart disease than nonsmokers. The initial presentation was less severe in terms of hemodynamic status, and angiography showed less complex coronary involvement in smokers. The overall mortality rate was 5.4% for current smokers and 9.9% for nonsmokers (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.47-0.58; p < .001). The gap in risk was attenuated after multivariable adjustment but remained statistically significant (HR, 0.85; 95% CI, 0.76-0.95; p = .005). Propensity score matching corroborated the results of reduced mortality among current smokers (6.7% vs. 7.6%; p = .005). CONCLUSIONS: In this study, in which the patients received up-to-date treatment options, smoking was associated with a 48% decrease in the risk of all-cause mortality at 1 year after AMI.

Long-term outcomes following anterior foraminotomy for one- or two-level cervical radiculopathy.

PURPOSE: Anterior foraminotomy (AF) is a surgical treatment for unilateral cervical radiculopathy that avoids fusion-related complications, but its long-term outcome has yet to be investigated. To clarify the efficacy of AF, the author retrospectively collected long-term data regarding the results of this technique. METHODS: Of 50 patients who underwent AF between November 1999 and June 2005, those who were followed for more than 6 years (n = 44) were enrolled in this study. The parameters studied included the number of revisions, additional surgeries, VAS/NDI, and Odom's criteria. Plain radiographs were also obtained pre- and postoperatively. RESULTS: At discharge, 98% of patients reported improvement, although 20 % temporarily experienced some residual symptoms. There were no other major postoperative complications. At final follow-up (FU, mean of 8.8 years), an excellent or good outcome was achieved in 39 patients (89%). There was no index level reoperation required, but two additional operations for symptomatic adjacent-segment degeneration were needed (4.5%). Six patients suffered from shoulder pain on the same side after surgery (mean onset: 3.6 years). At final FU, significant degeneration at the operated level was demonstrated on plain radiographs, resulting in a decreased range of motion. However, loss of lordosis of the segment was minimal. Radiographically, adjacent segment degeneration was noted in only 6 and 11% at the cranial and caudal segments, respectively. CONCLUSIONS: In this retrospective study, patients who underwent AF for one- or two- level cervical radiculopathy showed a good long-term outcome with minimal adjacent segment degeneration. However, more data should be collected to clarify possible associations with these findings, such as delayed shoulder problems and aggravation of degeneration at the operated level.

Radiologic risk factors associated with development of myelopathy in patients with ossification of the posterior longitudinal ligament of the cervical spine.

STUDY DESIGN: Retrospective Cohort Study OBJECTIVE: Myelopathy following ossification of the posterior longitudinal ligament (OPLL) is one of the devastating clinical features in these patients, while we still know little about which factors are associated with development of myelopathy. We evaluated the difference of radiologic measurements between OPLL patients with or without myelopathy and searched for the clinical significance with emphasis on the impact of dynamic motion. METHODS: 305 patients diagnosed of OPLL were enrolled for retrospective review. They were divided into two groups according to the coexistence of radiographic evidence of myelopathy. Demographic data as well as radiologic measures including the presence of disc degeneration (DD), anterior-posterior diameter (APD) of central canal, canal compromise (CC) ratio, global and segmental range of motion (gROM and sROM), OPLL type (morphologic classification) and K-line were collected. RESULTS: APD (odds ratio (OR); 0.411), CC ratio (OR; 1.100) and sROM (OR; 1.371) were significantly associated with the presence of myelopathy in the multivariate analysis. While the statistically significant factors were same in OPLLs with CC larger than 50%, presence of DD (OR; 4.509) and sROM (OR; 1.295) were significantly associated with myelopathy but not the CC itself in OPLLs with CC smaller than 50%. CONCLUSIONS: We discovered that the APD, CC ratio and sROM had significant association with development of myelopathy in OPLLs. And the presence of dynamic factors had significant association with myelopathy in OPLLs with smaller CC ratios. This observation and its clinical significance on development of myelopathy might enhance our understanding of OPLL.

Use of prophylactic perioperative antibiotics for lumbar spinal fusions: A nationwide population-based cohort study.

BACKGROUND: Perioperative prophylactic antibiotic (PPA) use in spine surgery is known to reduce the rate of surgical site infections. In the past decade, several evidence-based guidelines have been published and surveillance systems to monitor the proper use of antimicrobials had been adapted by many institutes. OBJECTIVE: To report the trends of PPA prescription in lumbar fusion surgeries nationwide in the Republic of Korea. METHODS: This is a nationwide registry study. Using the population-based data from the Republic of Korea provided by the Korean Health Insurance Review and Assessment Service, data of all lumbar spinal fusion surgeries performed between 2010 and 2018 in adult patients (age ≥19 years) were reviewed. RESULTS: The most frequently used antibiotics were first-generation cephalosporins, which accounted for 38.2 % of total PPA prescriptions and were prescribed in 58.96 % of lumbar fusion surgeries. A gradual increase in prescription trends was observed. The second most frequently used PPAs were second-generation cephalosporins, which showed decrease in use from 2016. The frequency of vancomycin prescriptions gradually increased over the observation period and showed an almost four-fold increase in 2018 compared to 2010. First- and second-generation cephalosporins were prescribed less frequently to patients with renal disease. CONCLUSION: The pattern of PPA use has changed remarkably over the observation period. Furthermore, specific differences in PPA prescriptions were observed among patients with certain co-morbidities.

Intervertebral disc organ-on-a-chip: an innovative model to study monocyte extravasation during nucleus pulposus degeneration.

Degenerative cascades of the intervertebral disc (IVD) are characterized by the presence of immune cells like monocytes, macrophages, and leukocytes, which contribute to inflammation. Previous in vitro studies on monocyte chemotaxis in the presence of chemical or mechanical stimulation were unable to establish the effects of endogenous stimulating factors from resident IVD cells, or fully understand macrophage and monocyte differentiation pathways in IVD degeneration. Our study simulates monocyte extravasation using a fabricated microfluidic chemotaxis IVD organ-on-a-chip (IVD organ chip), which models the geometry of IVD, chemoattractant diffusion, and infiltration of immune cells. Additionally, the fabricated IVD organ chip mimics stepwise monocyte infiltration and differentiation into macrophages in the degenerative nucleus pulposus (NP) induced by IL-1ß. We find that naïve NP cells do not recruit THP-1 monocyte-like cells, but degenerative NP cells recruit and accumulate macrophages through chemo-gradient channels. Furthermore, the differentiated and migrated THP-1 cells show phagocytic activity around inflammatory NP cells. Our in vitro model of monocyte chemotaxis with degenerative NP on an IVD organ chip depicts the sequential processes of monocyte migration/infiltration, monocyte-to-macrophage differentiation, and accumulation. Using this platform to gain a deeper understanding of monocyte infiltration and differentiation processes can provide insights into the pathophysiology of the immune response in degenerative IVD.

Current Knowledge and Future Therapeutic Prospects in Symptomatic Intervertebral Disc Degeneration.

Intervertebral disc (IVD) degeneration is the main source of intractable lower back pain, and symptomatic IVD degeneration could be due to different degeneration mechanisms. In this article, we describe the molecular basis of symptomatic IVD degenerative disc diseases (DDDs), emphasizing the role of degeneration, inflammation, angiogenesis, and extracellular matrix (ECM) regulation during this process. In symptomatic DDD, pro-inflammatory mediators modulate catabolic reactions, resulting in changes in ECM homeostasis and, finally, neural/vascular ingrowth-related chronic intractable discogenic pain. In ECM homeostasis, anabolic protein-regulating genes show reduced expression and changes in ECM production, while matrix metalloproteinase gene expression increases and results in aggressive ECM degradation. The resultant loss of normal IVD viscoelasticity and a concomitant change in ECM composition are key mechanisms in DDDs. During inflammation, a macrophage-related cascade is represented by the secretion of high levels of pro-inflammatory cytokines, which induce inflammation. Aberrant angiogenesis is considered a key initiative pathologic step in symptomatic DDD. In reflection of angiogenesis, vascular endothelial growth factor expression is regulated by hypoxia-inducible factor-1 in the hypoxic conditions of IVDs. Furthermore, IVD cells undergoing degeneration potentially enhance neovascularization by secreting large amounts of angiogenic cytokines, which penetrate the IVD from the outer annulus fibrosus, extending deep into the outer part of the nucleus pulposus. Based on current knowledge, a multi-disciplinary approach is needed in all aspects of spinal research, starting from basic research to clinical applications, as this will provide information regarding treatments for DDDs and discogenic pain.

Adipokine human Resistin promotes obesity-associated inflammatory intervertebral disc degeneration via pro-inflammatory cytokine cascade activation.

Adipokine human Resistin (hResistin), is known to be associated with insulin resistance and secrete low-grade pro-inflammatory cytokines in obesity. Although studies on low-grade inflammation of adipokine hResistin are known, studies on the effects and mechanisms of intervertebral disc degeneration (IVDD) are still lacking. Thus, we investigated the adipokine hResistin with or without pro-inflammatory cytokine IL-1ß in intervertebral disc (IVD) cells such as human annulus fibrosus (hAF) and nucleus pulposus (hNP). The protein expression changes in IL-1ß, IL-6, IL-8, MMP-1, MMP-3, and MMP-13, induced by the combined-hResistin and IL-1ß stimulation on hAF cells, was significantly greater than that of the same induced by mono-IL-1ß stimulation. Similarly, in the case of the protein expression change of inflammatory mediators induced by the combined-hResistin and IL-1ß stimulation on hNP cells was also significantly greater than that of the same induced by mono-IL-1ß stimulation. These results improve understanding of hResistin on inflammatory IVDD but also with other obesity-related inflammatory diseases.

Characteristics of Sagittal Spinopelvic Alignment Changes After Symptom Relief After Simple Lumbar Decompression.

BACKGROUND: Sagittal spinopelvic alignment (SSPA) parameters are essential for the diagnosis of adult spinal deformities (ASDs) and their progression. Certain clinical symptoms that occur in patients with lumbar spinal stenosis (LSS) and herniated nucleus pulposus (HNP) may distort the SSPA and mimic ASD. OBJECTIVE: To differentiate SSPA in symptomatic patients from asymptomatic patients within 10 minutes in the standing position. METHODS: This retrospective cohort study evaluated changes in SSPA after simple lumbar decompression surgery in patients with LSS and HNP. Relative sagittal alignment (RSA), relative pelvic version, relative lumbar lordosis (RLL), Lordosis Distribution Index (LDI), and global alignment and proportion (GAP) values were calculated using the conventional Schwab classification method. First, the preoperative and postoperative SSPA parameters were compared. Second, patients were subgrouped into symptomatic within 10 minutes of standing (SP group) and other symptoms of LSS and HNP as controls. Changes in SSPA parameters after symptom relief after simple lumbar decompression surgery were compared between the two groups. RESULTS: Overall, all SSPA parameters improved after surgery. However, after subgrouping, patients in the control group did not show significant SSPA alterations, except for LDI, whereas patients in the SP group significantly improved in terms of their RSA, RLL, LDI, and GAP values after symptom relief after surgery. CONCLUSION: Patients with pain on standing within 10 minutes showed significant correction in RSA, RLL, and GAP values after simple lumbar decompression. Therefore, it is important to observe such clinical symptoms to avoid misdiagnosis of ASD.

Elucidating the effect of mechanical stretch stress on the mechanism of ligamentum flavum hypertrophy: Development of a novel in vitro multi-torsional stretch loading device.

OBJECTIVE: We developed a novel multi-torsional mechanical stretch stress loading device for ligamentum flavum cells and evaluated its influence on the development of ligamentum flavum hypertrophy, a common cause of lumbar spinal canal stenosis. MATERIALS AND METHODS: Stretch strength of the device was optimized by applying 5% and 15% MSS loads for 24, 48, and 72 h. A cytotoxicity assay of human ligamentum flavum cells was performed and the results were compared to control (0% stress). Inflammatory markers (interleukin [IL]-6, IL-8), vascular endothelial growth factor [VEGF], and extracellular matrix (ECM)-regulating cytokines (matrix metalloproteinase [MMP]-1, MMP-3 and MMP-9, and tissue inhibitor of metalloproteinase [TIMP]-1 and TIMP-2) were quantified via enzyme-linked immunosorbent assay. RESULTS: Using our multi-torsional mechanical stretch stress loading device, 5% stress for 24 hour was optimal for ligamentum flavum cells. Under this condition, the IL-6 and IL-8 levels, VEGF level, and MMP-1, MMP-3, and TIMP-2 were significantly increased, compared to the control. CONCLUSION: Using the novel multi-torsional mechanical stretch stress loading device we confirmed that, mechanical stress enhances the production of inflammatory cytokines and angiogenic factors, and altered the expression of ECM-regulating enzymes, possibly triggering ligamentum flavum hypertrophy.

Transforming growth factor-ß induces epithelial to mesenchymal transition and suppresses the proliferation and transdifferentiation of cultured human pancreatic duct cells.

Pancreatic duct cells are considered a potential source of ß-cell regeneration, and transforming growth factor-ß (TGF-ß) has been suggested to perform an important role in these processes, but the underlying mechanism of the signal pathways, especially in humans, remains poorly understood. To evaluate the role of TGF-ß1, pancreatic duct cells were isolated from three brain-dead organ donors. Pancreatic cell clusters harvested after islet isolation were dispersed to single cells and cultured in monolayers, then treated with TGF-ß1. We analyzed the characteristics of the cultured cells, the TGF-ß1 intracellular signaling pathway, the proliferation, and transdifferentiation rates of the duct cells. We also evaluated the genes and protein expression patterns after TGF-ß1 treatment. After TGF-ß1 treatment, typical morphologic changes representative of EMT were observed and Erk1/2, JNK, and AKT phosphorylation, Ras downstream effectors, were increased. ß cell-specific transcription factors including PDX-1, Beta2/NeuroD, Ist-1, and NGN3 were markedly suppressed and the rate of transdifferentiation into ß cells was also suppressed. Genomic and proteomic analyses suggested that TGF-ß1 induces marked changes in a variety of structural genes and proteins associated with EMT. In conclusion, TGF-ß1 induces EMT in cultured human pancreatic duct cells, but suppresses its proliferation and transdifferentiation into ß cells. Our results are the first report of TGF-ß1 effects for EMT and ductal cell transdifferentiation and proliferation at the protein level in human pancreatic duct cells.

The effects of anterior cervical discectomy and fusion with stand-alone cages at two contiguous levels on cervical alignment and outcomes.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) using stand-alone cages is an effective method of treating degenerative disease. However, stand-alone cages are reported to have a relatively high incidence of implant subsidence with secondary kyphotic deformity particularly after multilevel ACDF. The purpose of our article was to investigate clinical and radiological outcomes after ACDF using stand-alone cages, at two contiguous levels, with a particular focus on changes in regional alignment and the correlation between alignment of the operated cervical levels and the entire cervical spine. METHODS: Twenty-seven patients with 54 levels and a mean age of 50.8 years were enrolled between January 2005 and August 2006. They underwent ACDF using polyetheretherketone cages packed with demineralized bone matrix without plate fixation at two contiguous levels. Mean follow-up period was 25.5 months (range, 13-60). Clinical outcome was evaluated using two Visual Analog Scales and the Neck Disability Index (NDI). We assessed fusion, regional alignment (RA) of the operated levels and cervical global alignment (GA) preoperatively in the immediate 1-week postoperative period and at the final follow-up. An interspinous distance ≥2 mm was used as an indicator of pseudoarthrosis at each level. FINDINGS: All patients showed improvements in clinical outcome, with 96% of patients showing mild NDI scores (<14). Radiological solid fusion was obtained at 48 of 54 levels (88.9%) and in 21 of 27 patients (77.8%). Lower cervical levels were significantly more vulnerable to pseudoarthrosis (100%). Fusion rate had no significant correlation with outcome (p > 0.05). RA of the operated levels was improved at the final follow-up compared with preoperatively in 76% of patients, although it had decreased compared with the immediate postoperative period due to subsidence in 84% of patients. In total, 80.8% of patients showed improvements in GA. Furthermore, improvements in RA showed a significant positive correlation with those in GA (p = 0.001), although improvement in RA and GA did not correlate significantly with clinical outcome (p > 0.05). CONCLUSIONS: Though some degree of subsidence occurred in most cases, RA had improved at the last follow-up compared with preoperatively, which contributed to the significant improvement in GA. However, improvement of RA and GA was not correlated with outcomes.

A Prospective, Multi-Center, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of the Synthetic Bone Graft Material DBM Gel with rhBMP-2 versus DBM Gel Used during the TLIF Procedure in Patients with Lumbar Disc Disease.

OBJECTIVE: This study is to evaluate the efficacy and safety of demineralized bone matrix (DBM) gel versus DBM gel with recombinant human bone morphogenetic protein-2 (rhBMP-2) used in transforaminal lumbar interbody fusion (TLIF). METHODS: This study was designed as a prospective, multi-center, double-blind method, randomized study. All randomized subjects underwent TLIF with DBM gel with rhBMP-2 group (40 patients) as an experimental group or DBM gel group (36 patients) as a control group. Post-operative observations were performed at 12, 24, and 48 weeks. The spinal fusion rate on computed tomography scans and X-rays films, Visual analog scale pain scores, Oswestry disability index and SF-36 quality of life (QOL) scores were used for the efficacy evaluation. The incidence rate of adverse device effects (ADEs) and serious adverse device effects (SADEs) were used for safety evaluation. RESULTS: The spinal fusion rate at 12 weeks for the DBM gel with rhBMP-2 group was higher with 73.68% compared to 58.82% for the DBM gel group. The 24 and 48 weeks were 72.22% and 82.86% for the DBM gel with rhBMP-2 group and 78.79% and 78.13%, respectively, for the DBM gel group. However, there were no significant differences between two groups in the spinal fusion rate at 12, 24, and 48 weeks post-treatment (p=0.1817, p=0.5272, p=0.6247). There was no significant difference between the two groups in the incidence rate of ADEs (p=0.3836). For ADEs in the experimental group, 'Pyrexia' (5.00%) was the most common ADE, followed by 'Hypesthesia', 'Paresthesia', 'Transient peripheral paralysis', 'Spondylitis' and 'Insomnia' (2.50%, respectively). ADEs reported in control group included 'Pyrexia', 'Chest discomfort', 'Pain', 'Osteoarthritis', 'Nephropathy toxic', 'Neurogenic bladder', 'Liver function analyses' and 'Urticaria' (2.86%, respectively). There was no significant difference between the two groups in the incidence rate of SADEs (p=0.6594). For SADE in the experimental group, ''Pyrexia' and 'Spondylitis' were 2.50%. SADE reported in the control group included 'Chest discomfort', 'Osteoarthritis' and 'Neurogenic bladder'. All SADEs described above were resolved after medical treatment. CONCLUSION: This study demonstrated that the spinal fusion rates of DBM gel group and DBM gel with rhBMP-2 group were not significantly different. But, this study provides knowledge regarding the earlier postoperative effect of rhBMP-2 containing DBM gel and also supports the idea that the longer term follow-up results are essential to confirm the safety and effectiveness.

A New Classification for Cervical Ossification of the Posterior Longitudinal Ligament Based on the Coexistence of Segmental Disc Degeneration.

OBJECTIVE: Classification systems for cervical ossification of the posterior longitudinal ligament (OPLL) have traditionally focused on the morphological characteristics of ossification. Although the classification describes many clinical features associated with the shape of the ossification, including the concept of spondylosis seems necessary because of the similarity in age distribution. METHODS: Patients diagnosed with OPLL who presented with increase signal intensity (ISI) on magnetic resonance imaging were surgically treated in our department. The patients were divided into two groups (pure versus degenerative) according to the presence of disc degeneration. RESULTS: Of 141 patients enrolled in this study, more than half (61%) were classified into the degenerative group. The pure group showed a profound male predominance, early presentation of myelopathy, and a different predilection for ISI compared to the degenerative group. The mean canal compromise ratio (CC) of the ISI was 47% in the degenerative group versus 61% in the pure group (p<0.0000). On the contrary, the global and segment motions were significantly larger in the degenerative group (p<0.0000 and p=0.003, respectively). The canal diameters and global angles did not differ between groups. CONCLUSION: Classifying cervical OPLL based on the presence of combined disc degeneration is beneficial for understanding the disorder's behavior. CC appears to be the main factor in the development of myelopathy in the pure group, whereas additional dynamic factors appear to affect its development in the degenerative group.