A Comparison Between Cortical Bone Trajectory Screws And Traditional Pedicle Screws in Patients With Single-Level Lumbar Degenerative Spondylolisthesis: Five-Year Results.

STUDY DESIGN: A retrospective observational study. OBJECTIVE: This study investigated the clinical and radiological results of using cortical bone trajectory (CBT) screws versus traditional pedicle (TP) screws in transforaminal lumbar interbody fusion (TLIF) during a five-year follow-up of patients with single-level lumbar degenerative spondylolisthesis. SUMMARY OF BACKGROUND DATA: Few studies have compared five-year follow-up outcomes between CBT screws and TP screws in TLIF. MATERIALS AND METHODS: We reviewed outcome data of patients with single-level lumbar degenerative spondylolisthesis who underwent TLIF procedures with CBT screws (131 patients) or TP screws (80 patients) between 2011 and 2015. Patient-reported clinical outcome data included Oswestry disability index scores and visual analog scale (VAS) scores for back and leg pain at baseline, six months, and one year, two years, and five years postoperatively. The radiographic fusion rate and prevalence of secondary surgery for adjacent segment disease were also measured. RESULTS: During the follow-up over five years, the CBT group had significantly lower VAS scores for back pain ( P <0.0001, respectively). At two years after surgery, the CBT group had significantly higher VAS scores for leg pain ( P =0.007). At five years postoperatively, no significant differences existed in the VAS score for leg pain or in the Oswestry disability index score between the two groups. Radiographic fusion rates (CBT vs. TP: 95.5% vs. 95.9%; P =0.881) and adverse events during the five years after surgery were not significantly different. At two years postoperatively, the prevalence of secondary surgery to treat adjacent segment disease was significantly different between the two groups (CBT vs . TP: 13.7% vs. 5.0%; P =0.044). CONCLUSIONS: Our results suggest that, during a five-year followup, CBT screws for TLIF were an effective treatment compared to TP screws in the setting of single-level lumbar degenerative spondylolisthesis. However, when using CBT screws for TLIF, surgeons should consider the higher rate of secondary procedures to treat symptomatic adjacent segment disease.

Changes in retro-odontoid mass after upper cervical spine surgery.

A non-neoplastic mass posterior to the dens is termed a retro-odontoid mass (R-OM). This retrospective study evaluated radiographic and clinical outcomes and R-OM changes after upper cervical spine surgery. This study included 69 patients who underwent upper cervical spine surgery, including atlantoaxial fusion, occipitocervical fusion, or decompression. All patients underwent preoperative magnetic resonance imaging (MRI). Six-month follow-up MRI examinations were performed in 30 patients who had preoperative R-OMs. Radiographic outcomes of the anterior and posterior atlantodental intervals were measured using X-rays and computed tomography. The R-OM and space available for the cord (SAC) were measured using MRI. Clinical outcomes were evaluated using neck and arm pain visual analog scales, the Japanese Orthopedic Association score, the neck disability index, and the patient-reported subjective improvement rate. The anterior atlantodental interval decreased, while the posterior atlantodental interval and SAC increased postoperatively. Among the clinical outcomes, the neck and arm pain and the neck disability index decreased postoperatively, while the Japanese Orthopedic Association score increased. All clinical and radiographic outcomes improved postoperatively. The R-OM either decreased in size or disappeared after fusion surgery in all cases, except in one patient who underwent decompression surgery. In conclusion, stabilization through fusion surgery is essential for treating R-OM.

Direct Internal Fixation for Unstable Atlas Fractures.

PURPOSE: To investigate the radiologic and clinical outcomes of direct internal fixation for unstable atlas fractures. MATERIALS AND METHODS: This retrospective study included 12 patients with unstable atlas fractures surgically treated using C1 lateral mass screws, rods, and transverse connector constructs. Nine lateral mass fractures with transverse atlantal ligament (TAL) avulsion injury and three 4-part fractures with TAL injury (two avulsion injuries, one TAL substance tear) were treated. Radiologic outcomes included the anterior atlantodental interval (AADI) in flexion and extension cervical spine lateral radiographs at 6 months and 1 year after treatment. CT was also performed to visualize bony healing of the atlas at 6 months and 1 year. Visual Analog Scale (VAS) scores for neck pain, Neck Disability Index (NDI) values, and cervical range of motion (flexion, extension, and rotation) were recorded at 6 months after surgery. RESULTS: The mean postoperative extension and flexion AADIs were 3.79±1.56 (mean±SD) and 3.13±1.01 mm, respectively. Then mean AADI was 3.42±1.34 and 3.33±1.24 mm at 6 months and 1 year after surgery, respectively. At 1 year after surgery, 11 patients showed bony healing of the atlas on CT images. Only one patient underwent revision surgery 8 months after primary surgery due to nonunion and instability findings. The mean VAS score for neck pain was 0.92±0.99, and the mean NDI value was 8.08±5.70. CONCLUSION: C1 motion-preserving direct internal fixation technique results in good reduction and stabilization of unstable atlas fractures. This technique allows for the preservation of craniocervical and atlantoaxial motion.

Nonclinical Safety Pharmacology Study of the Herbal Product HAD-B1.

HAD-B1 is a Korean herbal formula designed to treat solid tumors, and through cell experiments, it has proven to have an anticancer effect. The current study aims to test the safety of HAD-B1. This experiment is under the regulation of ICH. In order to find if HAD-B1 has any effect on the CNS, 0, 500, 1000, and 2000 mg/kg/day of HAD-B1 were orally administered to male and female rats once. To discover any effect on the respiratory system, 0, 500, 1000, and 2000 mg/kg/day of HAD-B1 were orally given to male rats followed by measuring the respiratory rate, tidal volume, and minute respiratory volume. To assess the possibility of a delayed QT period as a result of the drug administration, hERG analysis was conducted at 0, 0.1, 0.3, and 1 µg/ml. To assess any effect on the cardiovascular system, 0, 500, 1000, and 2000 mg/kg/day of HAD-B1 were orally given to male beagle dogs once followed by temperature, blood pressure, ECG, and heart rate analyses. There were no clinically significant changes in both male and female rats on assessing any effects on the CNS. There were no clinically significant changes in male rats' respiratory assessment. There were no clinically significant changes in hERG analysis results. There were no clinically significant changes in the cardiovascular system of male beagle dogs. Our results demonstrate that HAD-B1 is a safe herbal formula that does not have a clinically significant effect on the CNS, respiratory, and cardiovascular systems.

Perfluorooctane sulfonate and bisphenol A induce a similar level of mast cell activation via a common signaling pathway, Fyn-Lyn-Syk activation.

Perfluoroalkyl compounds (PFCs) as food contaminants are widely distributed persistent organic pollutants (POPs) and have been suggested to induce immune dysfunction. However, their effects on immune function are not conclusive. Mast cells play a central role in allergic and non-allergic inflammatory responses. Therefore, we have examined the effects of PFCs (PFHxS, PFOA, PFOS) on mast cell-mediated inflammatory responses using in vitro mouse bone marrow-derived mast cells (BMMCs) and human mast cells (HMC-1) and in vivo mice model. The effects of PFCs were compared with those of bisphenol A (BPA), a well-studied environmental pollutant. Among PFCs tested, PFOS had the highest effects. Both PFOS and BPA increased degranulation and production of inflammatory eicosanoids in mast cells at a similar level, which subsequently led to increased skin edema and serum LTC4 and PGD2 in mice. Both PFOS and BPA increased not only downstream signaling (PLCγ1, AKT, ERK), but also upstream signaling (Fyn, Lyn, Syk/LAT) in mast cells. Taken together, PFOS and BPA induce mast cell-mediated inflammatory responses via a common signaling pathways. Our results may help establish the scientific basis for understanding the etiology of mast cell-mediated inflammatory responses and improve the immune dysfunction risk assessment for emerging POPs such as PFCs.

Hypoxia Regulates the Extracellular Matrix via Mitogen-Activated Protein Kinases Pathway in Cells Retrieved from the Human Intervertebral Disc.

PURPOSE: The present study aimed to identify the physiological characteristics of cells by investigating the change in gene expression and protein levels during extracellular matrix (ECM) synthesis in the intervertebral disc (IVD) under hypoxic conditions. MATERIALS AND METHODS: To test the effect of oxygen on cell growth and ECM synthesis of chondrocyte-like cells, the cells from IVD were separated and cultured in two hypoxia-mimicking systems: chemical hypoxic conditions using deferoxamine (DFO), and physiological hypoxic conditions using a hypoxic chamber for 7 days. Chondrocyte like cells cultured without DFO and under the normal oxygen concentration (21% O2 and 5% CO2, 37°C) served as the controls. RESULTS: Chondrocyte-like cells cultured in the presence of 6% oxygen demonstrated a 100% increase in cellular proliferation compared to the control. The cells treated with chemical hypoxic conditions demonstrated a dose-dependent increase in the mRNA expression of glucose transporter-1, GAPDH, aggrecan, and type II collagen on Day 1. When treated with 100 µM DFO, the cells showed a 50% increase in the levels of proteoglycan protein on Day 7. The cells treated with chemical hypoxic condition demonstrated increase in sulfated glycosaminoglycan (GAG) protein levels on Day 7. Moreover, the cells cultured in the presence of 6% oxygen showed a 120% increase in sulfated GAG levels on Day 7. CONCLUSION: The oxygen concentration had an important role in the viability, proliferation, and maturation of chondrocyte-like cells in IVD. In addition, chondrocyte-like cells are sensitive to the concentration of oxygen.

Transient fixation of L4 vertebra preserves lumbar motion and function in Lenke Type 5C and 6C scoliosis.

This study investigated the efficacy of a novel surgical method that relies on the transient fixation of L4 in Lenke Type 5C and 6C adolescent idiopathic scoliosis. Thirty-six transient surgically treated L4 fixation patients were retrospectively evaluated. The first surgery involved mechanical correction of scoliosis; the lowest instrumented vertebra (LIV) was L4. After an average of 1.3 years (range, 0.3-3.4), the second surgery to remove transient L4 pedicle screws was performed. Radiographic parameters and SRS-22 scores were measured. Cobb's angle, coronal balance, LIV tilting angle, and LIV coronal disc angle clearly improved after the first surgery (p < 0.01). After the second surgery, the corrected Cobb angle (p = 0.446) and coronal balance were maintained (p = 0.271). Although L3/S1 lumbar lordosis decreased after the first surgery (p < 0.01), after removal of transient L4 pedicle screws, it recovered slightly (p = 0.03). Similarly, the preoperative L3/4 lateral disc mobility eventually recovered after transient L4 screw removal (p < 0.01). The function domain of the SRS-22 showed better scores after removal of transient L4 screws (p = 0.04). L4 transient fixation surgery is beneficial for Lenke Type 5C and 6C scolioses that do not fully satisfy LIV (L3) criteria. It preserves L3/4 disc motion, increases functional outcomes, and maintains spinal correction and coronal balance.

Chelidonine Induces Apoptosis via GADD45a-p53 Regulation in Human Pancreatic Cancer Cells.

Chelidonium majus has been used as a traditional medicine in China and western countries for various diseases, including inflammation and cancer. However, the anti-cancer effect of chelidonine, a major compound of C. majus extracts, on pancreatic cancer remains poorly understood. In this study, we found that treatment with chelidonine inhibited proliferation of BxPC-3 and MIA PaCa-2 human pancreatic cancer cells. Annexin-V/propidium iodide staining assay showed that this growth inhibitory effect of chelidonine was induced through apoptosis. We found that chelidonine treatment upregulated mRNA levels and transcription factor activity in both cell lines. Increases in protein expression levels of p53, GADD45A, p21 and cleaved caspase-3 were also observed, with more distinct changes in MIA PaCa-2 cells compared to the BxPC-3 cells. These results suggest that chelidonine induces pancreatic cancer apoptosis through the p53 and GADD45A pathways. Our findings provide new insights into the use of chelidonine for the treatment of pancreatic cancer.

Acrylamide and its metabolite induce neurotoxicity via modulation of protein kinase C and AMP-activated protein kinase pathways.

Acrylamide is known as a neurotoxicant found in commonly consumed food as well as in human body. However, the underlying mechanisms involved in neurotoxicity by acrylamide and its metabolite, glycidamide remain largely unknown. In this study, we have examined the interplay between CYP2E1, AMPK, ERK and PKC in acrylamide-induced neurotoxicity associated with autophagy in PC12 cells. Acrylamide-induced cell death was mediated by CYP2E1 expression and the activation of ERK, PKC-ɑ and PKC-δ, whereas AMPK knockdown exacerbated the acrylamide-induced neurotoxic effects. PKC-ɑ, but not PKC-δ, plays an upstream regulator of ERK and AMPK. Moreover, AMPK activation suppressed ERK, and CYP2E1 and AMPK bilaterally inhibit each other. Furthermore, acrylamide increased autophagy with impaired autophagic flux, evidenced by the increased beclin-1, LC3-II and p62 protein. Acrylamide-induced neuronal death was ameliorated by 3-methyladenine, an autophagy inhibitor, whereas neuronal death was exacerbated by chloroquine, a lysosomal inhibitor. Interestingly, PKC-δ siRNA, but not PKC-ɑ siRNA, dramatically reduced acrylamide-induced beclin-1 and LC3-II levels, whereas AMPK siRNA further increased beclin-1, LC3-II and p62 protein levels. Glycidamide, a major metabolite, mimicked acrylamide only with a higher potency. Taken together, acrylamide- and glycidamide-induced neurotoxicity may involve cytotoxic autophagy, which is mediated by interplay between PKCs and AMPK pathways.

Lumbar Spinal Stenosis: Pathophysiology and Treatment Principle: A Narrative Review.

Patients with lumbar spinal stenosis may exhibit symptoms such as back pain, radiating pain, and neurogenic claudication. Although long-term outcome of treatments manifests similar results for both nonsurgical and surgical treatments, positive effects such as short-term improvement in symptoms and decreased fall risk may be expected with surgery. Surgical treatment is basically decompression, and a combination of treatments can be added depending on the degree of decompression and the accompanying instability. Recently, minimally invasive surgery has been found to result in excellent outcomes in the treatment of lumbar spinal stenosis. Therefore, better treatment effects can be anticipated with an approach aimed at understanding the overall pathophysiology and treatment methods of lumbar spinal stenosis.

Prevalence of Gastrointestinal and Cardiovascular Risk in Patients with Degenerative Lumbar Spinal Disease.

BACKGROUND: Limited information is available about the proportion of patients with degenerative lumbar spinal disease (DLSD) who have gastrointestinal (GI) and cardiovascular (CV) risk factors. Many DLSD patients are prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) that are known to carry risks to the GI and CV systems by increasing GI bleeding and thromboembolic events. This study aimed to measure the prevalence of GI and CV risk in patients with DLSD and to ascertain whether the prescription of NSAIDs is in line with current guidelines. METHODS: This study included 153 patients with symptomatic DLSD who were planning to undergo lumbar spinal surgery. The GI profile was checked using the GI Standardized Calculator of Risk for Event system and CV risk was evaluated using the presence of metabolic syndrome. The conformity of the prescription of NSAIDs was investigated according to the recommendations in current guidelines. RESULTS: More than half of the patients (59.5%) had high or very high GI risk, and 66% of the patients were diagnosed with metabolic syndrome, which corresponds with CV risk. The rate of simultaneous GI and CV risk was 40.5% (n = 62 / 153; gastrointestinal Standardized Calculator of Risk for Event, > high and metabolic syndrome, yes). The actual prescription of NSAIDs was not in accordance with current guidelines. CONCLUSIONS: Two out of 3 patients had GI or CV risk factors, and approximately 40% of patients had both. Detailed assessment of GI and CV risk in patients with DLSD by using effective evaluation tools is mandatory for optimal medical treatment.

Hand grip strength as a surrogate marker for postoperative changes in spinopelvic alignment in patients with lumbar spinal stenosis.

There are a few studies on the postoperative changes in sagittal alignment and corresponding factors, including hand grip strength (HGS) and muscle performance tests for lumbar spinal stenosis (LSS). Thus, we aimed to determine whether HGS can be a surrogate marker for global sagittal alignment changes after decompression with fusion surgery for LSS. This retrospective observational study included 91 patients who underwent spine fusion surgery for LSS. Radiological spinopelvic parameters, including sagittal vertical axis (SVA), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), global tilt (GT), and T1 pelvic angle (T1PA), were analyzed preoperatively and 1 year after posterior decompression and fusion surgery. To assess muscle performance, the 6-m walk (SMT), timed up and go (TUGT), and sit-to-stand (STS) tests were conducted. The relationship between HGS and postoperative SVA was examined through multiple linear regression analysis. Additionally, the relationship between HGS and preoperative/postoperative radiologic spinopelvic parameters and muscle performance test results was analyzed through Pearson's correlation. HGS was significantly correlated with age, preoperative and postoperative SVA, and the muscle performance tests. Furthermore, HGS was a factor that can significantly influence postoperative SVA changes in multiple linear regression analyses. Therefore, HGS may be a good predictor of postoperative SVA change.

High Pelvic Incidence Is Associated with Disease Progression in Nontraumatic Osteonecrosis of the Femoral Head.

BACKGROUND: Although several factors exacerbate osteonecrosis of the femoral head (ONFH), little is known about whether pelvic sagittal parameters are associated with a greater risk of ONFH progression. QUESTIONS/PURPOSES: The purpose of this study was to investigate the association between pelvic sagittal parameters and disease progression (collapse of the femoral head) in patients with nontraumatic ONFH. METHODS: From March 2010 through December 2016, we saw 401 patients with unilateral ONFH diagnosed at an outpatient clinic using plain radiography and MRI that were retrospectively reviewed. Of those, 276 patients met our inclusion criteria: Association Research Circulation Osseous (ARCO) Stage I or II nontraumatic unilateral ONFH without femoral head collapse, older than 18 years, and no prior surgical treatment. In all, 74% (203 of 276) of hips had complete follow-up (clinical and radiographic) at a minimum of 2 years. The pelvic sagittal parameters (pelvic incidence, pelvic tilt, and sacral slope) of all patients were measured with standing radiographs by two observers. Progression of disease and potential collapse of the femoral head of all patients (ARCO Stage ≥ III) was examined using radiography every 2 to 3 months after the first outpatient clinic visit. If patients with intractable pain associated with collapse of the femoral head did not respond to nonoperative treatment, THA was performed during the follow-up period. The patients were divided into two groups for comparison: those whose femoral head collapsed within 12 months (rapid progression group) and those whose femoral head did not collapse (nonrapid progression group). The rapid progression group consisted of 49 men and 55 women with a mean age of 55 years; the nonrapid progression group consisted of 60 men and 39 women with a mean age of 56 years. Factors such as age, sex, BMI, size of necrotic lesions, location of necrosis, necrosis risk factor associated with the rapid progression of disease were analyzed using an exploratory univariate analysis followed by a multivariate analysis. RESULTS: Pelvic incidence (53° ± 9° versus 49° ± 7°; p < 0.01) and sacral slope (38° ± 9° versus 33° ± 7°; p < 0.01) were greater in the rapid progression group than in the non-rapid progression group. After accounting for potentially confounding variables like age, sex, BMI, size of necrotic lesions, location of necrosis, and necrosis risk factors, the only variable we found that was independently associated with more rapid disease progression was high (> 55°) pelvic incidence (odds ratio, 0.95 [95% CI 0.91 to 0.99]; p = 0.03). CONCLUSIONS: After controlling for potential confounders such as age, sex, BMI, size of necrotic lesions, location of necrosis, and necrosis risk factors, we found that a high pelvic incidence was associated with a greater likelihood of femoral head collapse in patients with nontraumatic ONFH. Assessing pelvic sagittal parameters in patients with early nontraumatic ONFH may help anticipate which patients are at risk for femoral head collapse, but future prospective studies are needed to confirm these findings. LEVEL OF EVIDENCE: Level III, therapeutic study.

Hand grip strength can predict clinical outcomes and risk of falls after decompression and instrumented posterolateral fusion for lumbar spinal stenosis.

BACKGROUND CONTEXT: There has been limited research on the association between hand grip strength (HGS) as one of the diagnostic criteria for sarcopenia and surgical outcomes of lumbar spinal stenosis (LSS). PURPOSE: We aimed to determine the effect of HGS on surgical outcomes and risk of fall in patients with LSS. STUDY DESIGN: This is a retrospective observational study. PATIENT SAMPLE: We included 200 patients who underwent spinal surgery for LSS. OUTCOME MEASURES: We recorded clinical outcome parameters, including Oswestry Disability Index (ODI), Euro-QOL (EQ-5D), and visual analog scale (VAS) scores for back or leg pain. To assess the risk of fall we used HGS and four functional mobility tests (alternative step test, six-meter walk test, timed up and go test, sit-to-stand test). MATERIALS AND METHODS: ODI, EQ-5D, and VAS scores for back and leg pain were assessed preoperatively and 1 year after surgery. The four functional mobility tests were assessed at each time point during the 1-year follow-up period to assess the risk of fall in patients with LSS. We divided the patient cohort according to sex and allocated them into two different groups based on HGS: high HGS (≥26 kg for men, n=26; ≥18 kg for women, n=35), and low HGS (<26 kg for men, n=48; <18 kg for women, n=91). The pre- and postoperative ODI, EQ-5D, and VAS scores for back and leg pain, as well as the functional mobility test results, and demographic data were compared between the two groups using independent t tests. Correlations between HGS and clinical outcome parameters were analyzed using Pearson correlation. RESULTS: In women and men, HGS correlated with the preoperative/postoperative ODI (r1=-0.217/r2=-0.345 in women, and r1=-0.384/r2=-0.411 in men) and EQ-5D scores (r1=0.190/r2=0.309 in women, and r1=0.373/r2=0.467 in men). HGS also correlated with the four postoperative results for the functional mobility tests: alternative step test (r=-0.238 in women, r=-0.431 in men), six-meter walk test (r=-0.232 in women, r=-0.282 in men), timed up and go test (r=-0.285 in women, r=-0.359 in men), and sit-to-stand test (r=-0.238 in women, r=-0.251 in men). The preoperative and postoperative ODI and EQ-5D scores in the high HGS group were superior to those in the low HGS group. Among the four functional mobility tests, preoperative and postoperative six-meter walk test results showed improvements in the high HGS group. CONCLUSIONS: Considering the multifactorial nature of falls, HGS may be a useful surrogate marker for predicting the risk of falls and clinical outcomes in patients with LSS.

Comparison of survival analysis between surgical and non-surgical treatments in Duchenne muscular dystrophy scoliosis.

BACKGROUND CONTEXT: There are still controversies about the effects of spinal surgeries for Duchenne muscular dystrophy (DMD) scoliosis on functional outcome, respiratory function, and the survival rate. PURPOSE: The purpose of this retrospective investigation was to compare the clinical course over time between the patients who were treated surgically and those who were treated nonsurgically. Through this comparison, we tried to determine how surgical treatment could affect the functional status, pulmonary function, and survival rate in patients with DMD scoliosis. STUDY DESIGN/SETTING: Single-center retrospective cohort study. PATIENT SAMPLE: We reviewed the clinical data of 199 male patients with DMD scoliosis who were followed up at our center for an average of 6.4 years between 2003 and 2017. OUTCOME MEASURES: The basic radiologic parameters evaluated include the Cobb angle and pelvic obliquity on a whole spine X-ray. Further, the Swinyard scale for functional status, forced vital capacity (FVC) for respiratory function, and mortality were compared between the surgical group and nonsurgical group. METHODS: The radiologic parameters and Swinyard scale stage were compared between the surgical group and nonsurgical group at baseline and 2, 5, and 10 years. For the FVC, serial changes every year were investigated in both groups. Mortality was surveyed between the surgical group and nonsurgical group. RESULTS: Of the 199 patients, 99 patients underwent the instrumented spinal fusion surgery and 100 patients in the nonsurgical group opted for conservative management. Radiologic results of the two groups were not different at baseline, but during the follow-up periods, the surgical group demonstrated better Cobb angles and pelvic obliquities. The surgical group showed a better functional status than did the nonsurgical group (6.7±0.9 versus [vs.] 7.2±0.7, p<.001). These functional differences between the groups were continuously observed during the follow-up period. Similarly, the FVC at baseline was higher in the surgical group than in the nonsurgical group (1005.7±421.4 mL vs. 787.3±574.1 mL, p=.005). Although FVC in the nonsurgical group consistently decreased during the follow-up (4.8% decrease/year), FVC in the surgical group increased up to the 2-year follow-up period compared with the baseline value and decreased during the follow-up period (2.8% decrease/year). Mortality was higher in the nonsurgical group than in the surgical group (n=22/100, 22.0% vs. n=8/99, 8.1%; p<.001) during an average follow-up duration of 6.4 years. Mean survival was longer in the surgical group than in the nonsurgical group (12.2 years vs. 8.3 years, hazard ratio=2.43, p=.02). CONCLUSIONS: Spinal surgery for DMD scoliosis improved the FVC for approximately 2 years postoperatively compared to non-surgical treatment. The surgical group had a better functional status and FVC at baseline than the non-surgical group. The positive effect of surgical treatment on the FVC is owing to scoliosis correction, which delayed the decrease of FVC and consequently extended the survival rate of the patients with DMD scoliosis.

The Effects of Anterior Cruciate Ligament Reconstruction on Individual Quadriceps Muscle Thickness and Circulating Biomarkers.

Anterior cruciate ligament reconstruction (ACLR) frequently results in quadriceps atrophy. The present study investigated the effect of ACLR on the muscle thickness of the different constituent muscles of the quadriceps and circulating biomarkers related to muscle atrophy and hypertrophy. Fourteen subjects underwent anterior cruciate ligament reconstruction following injury. Quadriceps muscle thicknesses were measured using ultrasound, and circulating biomarkers in the blood were measured using enzyme-linked immunosorbent assays (ELISAs) at the preoperative visit (PRE) and at two postoperative visits (PO1, PO2) in the early stages post-surgery. Differences between time points were analyzed using one-way repeated measures analysis of variance (ANOVA) tests. The most important finding was that severe muscle atrophy occurred in the vastus intermedius (VI) after ACLR (PRE: 20.45 ± 6.82 mm, PO1: 16.05 ± 6.13 mm, PO2: 13.18 ± 4.7 mm, F = 59.0, p < 0.001). Furthermore, the myostatin level was slightly increased, and IGF-1 was significantly reduced throughout the entire period. Therefore, we suggest that inducing selective hypertrophy in the vastus intermedius during the process of rehabilitation would be important for athletes and individuals who engage in explosive sports. Moreover, inhibiting myostatin level increases and maintaining IGF-1 levels in the early phase of recovery after ACLR to prevent muscle atrophy may provide a pharmaceutical option for rehabilitation after anterior cruciate ligament injury.

Regulation of MMP and TIMP expression in synovial fibroblasts from knee osteoarthritis with flexion contracture using adenovirus-mediated relaxin gene therapy.

PURPOSE: The aim of this study was to investigate the effects of relaxin (RLN) expression on fibrosis inhibition in synovial fibroblasts. MATERIALS AND METHODS: Tissue cells from patients with knee osteoarthritis and >30° flexion contractures were utilised. Synovial fibroblasts were activated by TGF-ß1 (two nanograms per millilitre) and then exposed to Ad-RLN as a therapeutic gene, adenovirus-lacZ construct as a marker gene, and SB505124 as an inhibitor for TGF-ß1 signal for 48 h. The mRNA expression levels of collagens and MMPs were analysed by reverse transcription-polymerase chain reaction. Also, fibronectin, phosphorylation of Smad2 and ERK1/2, alpha smooth muscle actin, TIMP-1, TIMP-2, MMP-1 and MMP-13 levels were estimated using western blotting, and the total collagen synthesis was assayed. RESULTS: Ad-RLN-transduced synovial fibroblasts demonstrated 17%, 13%, and 48% reduction in collagen I, III and IV mRNA expression levels, respectively, and a 40% decrease in MMP-3, MMP-8, 20% decrease in MMP-9, MMP-13 mRNA expression, compared to non-Ad-RLN-transduced cells. In protein expression, Ad-RLN-transduced synovial fibroblasts demonstrated 46% increase in MMP-1, 5% decrease in MMP-2, 51% increase in MMP-9, and 22% increase in MMP-13, compared to non-Ad-RLN-transduced cells. Ad-RLN-transduced synovial fibroblasts showed a 25% decrease in TIMP-1 and 65% decrease in TIMP-2 protein expression at 48h, compared to non-Ad-RLN-transduced cells. Ad-RLN-transduced synovial fibroblasts demonstrated a 45% inhibition of fibronectin in protein expression level and 38% decrease in total collagen synthesis at 48h, compared to non-Ad-RLN-transduced cells. CONCLUSION: Relaxin expression exerted anti-fibrogenic effects on synovial fibroblasts from patients with knee osteoarthritis and flexion contractures. Therefore, relaxin could be an alternative therapeutic agent during the initial stage of osteoarthritis with flexion contracture by exerting its anti-fibrogenic effects.

What is a Right Distal Fusion Level for Prevention of Sagittal Imbalance in Multilevel Posterior Cervical Spine Surgery: C7 or T1?

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: To evaluate the sagittal alignment and T1 slope after multilevel posterior cervical fusion surgery depending on the distal fusion level; C7 or T1, and find out the appropriate distal fusion level. SUMMARY OF BACKGROUND DATA: The sagittal balance of the cervical spine is known to be affected by cervical lordosis and T1 slope. However, T1 slope is not a constant parameter that can be frequently changed after the surgery. Furthermore, useful studies to help guide surgeons in decision-making as to the most appropriate distal level of fusion for cervical sagittal balance are very limited. MATERIALS AND METHODS: From 2014 to 2015, 50 patients who underwent multilevel posterior cervical fusion surgery were evaluated and followed up for >2 years. Group 1 was composed of 29 patients whose distal fusion level was C7. Group 2 was composed of 21 patients whose distal fusion level was T1. C1-C2 lordosis, C2-C7 lordosis, C2-C7 sagittal vertical axis (SVA), and T1 slope were measured on preoperative and the last follow-up. RESULTS: In group 1, C2-C7 SVA (23.1→30.4 mm, P=0.043) was worsened, and T1 slope (22.3→32.9 degrees, P=0.001) was increased after the surgery. In group 2, no significant change occurred in C2-C7 SVA after the surgery (25.3 →23.6 mm, P=0.648). The last follow-up T1 slope was similar with preoperative T1 slope (22.7→21.8 degrees, P=0.04) in group 2. CONCLUSIONS: This study showed that sagittal alignment became worse after the multilevel posterior cervical surgery when distal fusion level was stopped at C7, which was associated with increase of T1 slope. However, when we extended the distal fusion level to T1, T1 slope was not changed after the surgery. Therefore, sagittal alignment was maintained after the surgery. On the basis of the results of this study, we recommend distal fusion extends to T1. LEVEL OF EVIDENCE: Level III.

Effect of Sagittal Balance on Risk of Falling after Lateral Lumbar Interbody Fusion Surgery Combined with Posterior Surgery.

PURPOSE: To demonstrate the impact of correcting sagittal balance (SB) on functional outcomes of surgical treatment for degenerative spinal disease and actual falls via utilization of new minimally invasive lumbar fusion techniques via a lateral approach. MATERIALS AND METHODS: From November 2011 to March 2015, we enrolled 56 patients who underwent minimally invasive lateral lumbar interbody fusion (LLIF) and matched 112 patients receiving decompression/postero-lateral fusion (PLF) surgery for lumbar spinal stenosis. According to SB status using C7-plumb line-distance (C7PL) and surgery type, patients were divided into three groups: SB PLF, sagittal imbalance (SI) PLF, and LLIF groups. We then compared their outcomes. RESULTS: The mean C7PL was 6.2±13.6 mm in the SB PLF group, 72.9±33.8 mm in the SI PLF group, and 74.8±38.2 mm in the LLIF group preoperatively. Postoperatively, C7PL in only the LLIF group improved significantly (p=0.000). Patients in the LLIF group showed greater improvement in fall-related functional test scores than the SI PLF group (p=0.007 for Alternate-Step test, p=0.032 for Sit-to-Stand test). The average number of postoperative falls was 0.4±0.7 in the SB PLF group, 1.1±1.4 in the SI PLF group, and 0.8±1.0 in the LLIF group (p=0.041). Oswestry Disability Index and the Euro-QoL 5 dimension visual analogue scale scores also showed greater improvements in the LLIF group than in the SI PLF group at postoperative 1 year (p=0.003, 0.016). CONCLUSION: Surgical correction of SI in patients with lumbar spinal stenosis using a combination of minimal invasive LLIF and posterior surgery achieved better surgical outcomes and a lower incidence of actual falls than PLF surgery.

Efficacy and Safety of Different Aceclofenac Treatments for Chronic Lower Back Pain: Prospective, Randomized, Single Center, Open-Label Clinical Trials.

PURPOSE: Nonsteroidal anti-inflammatory drugs are a mainstay for medical treatment of chronic lower back pain (CLBP). Increased dose intervals for medication have been associated with increased patient adherence to prescriptions. The purpose of this clinical trial was to compare the efficacy and safety of a once daily dose of aceclofenac controlled release (CR) and a twice daily dose of aceclofenac for CLBP management. MATERIALS AND METHODS: A prospective, randomized, single center, open-label clinical trial was performed to compare the efficacy and safety of aceclofenac CR (200 mg once daily) to aceclofenac dose (100 mg twice daily). Fifty patients in each group were enrolled for the study. The primary end point was Visual Analogue Scale (VAS) change at baseline to that at 2 weeks after medication and safety profiles. Also, change in quality of life measured by EuroQoL 5D (EQ-5D) and Oswestry Disability Index (ODI) functional score for the lumbar spine were also assessed. RESULTS: Within groups at pre- and post-treatment, there were significant VAS reductions for aceclofenac CR and aceclofenac (p=0.028). EQ-5D increased significantly in both groups (p=0.037). ODI scores decreased significantly in both groups (p=0.012). However, there were no significant differences between aceclofenac CR and aceclofenac at pre- and post-treatment. Patients with aceclofenac CR showed significant increases in heartburn and indigestion and adverse gastrointestinal effects, compared to aceclofenac. CONCLUSION: In patients with CLBP, aceclofenac CR and aceclofenac demonstrated significant symptomatic pain relief, improvement in quality of life and functional scores. Aceclofenac CR slightly increased gastrointestinal adverse effects, such as heartburn and indigestion.