Novel Screw Placement Method for Extremely Small Lumbar Pedicles in Scoliosis.

Study Design: Consecutive case series. Objective: To propose a screw placement method in patients with extremely small lumbar pedicles (ESLPs) (<2 mm) to maintain screw density and correction power, without relying on the O-arm navigation system. Summary of Background Data: In scoliosis surgery, ESLPs can hinder probe passage, resulting in exclusion or substitution of the pedicle screws with a hook. Screw density affects correction power, making it necessary to maximize the number of screw placements, especially in the lumbar curve. Limited studies provide technical guidelines for screw placement in patients with ESLPs, independent of the O-arm navigation system. Methods: We enrolled 19 patients who underwent scoliosis correction surgery using our novel screw placement method for ESLPs. Clinical, radiological, and surgical parameters were assessed. After posterior exposure of the spine, the C-arm fluoroscope was rotated to obtain a true posterior-anterior view and both pedicles were symmetrically visualized. An imaginary pedicle outline was presumed based on the elliptical or linear shadow from the pedicle. The screw entry point was established at a 2 (or 10) o'clock position in the presumed pedicle outline. After adjusting the gear-shift convergence, both cortices of the transverse process were penetrated and the tip was advanced towards the lateral vertebral body wall, where an extrapedicular screw was placed with tricortical fixation. Results: Out of 90 lumbar screws in 19 patients, 33 screws were inserted using our novel method, without correction loss or complications during an average follow-up period of 28.44 months, except radiological loosening of one screw. Conclusions: Our new extrapedicular screw placement method into the vertebral body provides an easy, accurate, and safe alternative for scoliosis patients with ESLPs without relying on the O-arm navigation system. Surgeons must consider utilizing this method to enhance correction power in scoliosis surgery, regardless of the small size of the lumbar pedicle.

Therapeutic Extracellular Vesicles from Tonsil-Derived Mesenchymal Stem Cells for the Treatment of Retinal Degenerative Disease.

BACKGROUND: Retinal degenerative disease (RDD), one of the most common causes of blindness, is predominantly caused by the gradual death of retinal pigment epithelial cells (RPEs) and photoreceptors due to various causes. Cell-based therapies, such as stem cell implantation, have been developed for the treatment of RDD, but potential risks, including teratogenicity and immune reactions, have hampered their clinical application. Stem cell-derived extracellular vesicles (EVs) have recently emerged as a cell-free alternative therapeutic strategy; however, additional invasiveness and low yield of the stem cell extraction process is problematic. METHODS: To overcome these limitations, we developed therapeutic EVs for the treatment of RDD which were extracted from tonsil-derived mesenchymal stem cells obtained from human tonsil tissue discarded as medical waste following tonsillectomy (T-MSC EVs). To verify the biocompatibility and cytoprotective effect of T-MSC EVs, we measured cell viability by co-culture with human RPE without or with toxic all-trans-retinal. To elucidate the cytoprotective mechanism of T-MSC EVs, we performed transcriptome sequencing using RNA extracted from RPEs. The in vivo protective effect of T-MSC EVs was evaluated using Pde6b gene knockout rats as an animal model of retinitis pigmentosa. RESULTS: T-MSC EVs showed high biocompatibility and the human pigment epithelial cells were significantly protected in the presence of T-MSC EVs from the toxic effect of all-trans-retinal. In addition, T-MSC EVs showed a dose-dependent cell death-delaying effect in real-time quantification of cell death. Transcriptome sequencing analysis revealed that the efficient ability of T-MSC EVs to regulate intracellular oxidative stress may be one of the reasons explaining their excellent cytoprotective effect. Additionally, intravitreally injected T-MSC EVs had an inhibitory effect on the destruction of the outer nuclear layer in the Pde6b gene knockout rat. CONCLUSIONS: Together, the results of this study indicate the preventive and therapeutic effects of T-MSC EVs during the initiation and development of retinal degeneration, which may be a beneficial alternative for the treatment of RDD.

Bowel Injury and Insidious Pneumoperitoneum after Lateral Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective review of prospectively collected cases. PURPOSE: To report bowel injury cases and determine the incidence and risk factors of insidious pneumoperitoneum after lateral lumbar interbody fusion (LLIF). OVERVIEW OF LITERATURE: Minimally invasive LLIF is considered a safe surgical approach with a low risk of complications. Visceral injury after LLIF is rare and, to our knowledge, no studies on pneumoperitoneum after LLIF have been performed. Bowel injury is a catastrophic complication, but the clinical signs may not be apparent. After we encountered two cases of bowel injury after LLIF, we decided to perform computed tomography of the abdomen and pelvis (APCT) after surgery for all patients who underwent LLIF. METHODS: A total of 90 patients underwent APCT within 48 hours of surgery. Medical records were reviewed to determine each patient's age, sex, body mass index, medical and surgical histories, characteristics of LLIF procedures, and subjective symptoms and abnormal findings in the physical examination related to acute abdomen after surgery. Various parameters were compared between patients with and without pneumoperitoneum. RESULTS: Bowel injuries were identified in the first two patients and five patients (5.5%) were diagnosed with pneumoperitoneum only on APCT. We found that the greater the number of fused segments, the higher the incidence of postoperative bowel injury and/or pneumoperitoneum. The incidence was significantly high when the L2-3 level was included in the LLIF surgery. CONCLUSIONS: Pneumoperitoneum after LLIF indicates damage to the peritoneum and the presence of bowel injury that may lead to peritonitis. However, it is difficult to distinguish pneumoperitoneum and/or bowel injury from general abdominal pain after surgery because patients may present with a wide range of symptoms. We recommend that APCT be routinely performed after LLIF surgery in order to promptly identify pneumoperitoneum and bowel injury.

Spinopelvic parameters in degenerative spondylolisthesis.

The purpose of this study was to compare various sagittal spinopelvic parameters between patients with and without degenerative lumbar spondylolisthesis (DLS). A total of 165 patients who underwent surgery for low back and/or radicular pain were divided into two groups: those without DLS (non-DLS group; n = 85) and those with DLS (DLS group; n = 80). In all sagittal spinopelvic parameters, no significant difference was found between the non-DLS and DLS groups. The mean pelvic incidence (PI) value of the DLS group (56.4°) was almost similar to that of the non-DLS group (57.5°). The cross-sectional ratio of lumbar musculature was significantly smaller in the DLS group than in thenon-DLS group (p = 0.046). Contrary to the results of previous studies, a high PI may not be a predisposing factor for DLS development. Atrophy of back extensor muscles may play a role in the pathogenesis of DLS.

Does Sacral Slanting Affect Distal Adding-on in Lenke Type 1A Adolescent Idiopathic Scoliosis?

STUDY DESIGN: A retrospective clinical study. OBJECTIVE: The purpose of this study was to identify risk factors for postoperative distal adding-on in Lenke 1A adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Distal adding-on is a postoperative complication associated with the Lenke type 1A curve. Although various factors are known to cause postoperative adding-on, no study has reported a correlation between sacral slanting and adding-on. METHODS: A total of 126 consecutive patients who underwent posterior correction and fusion surgery for Lenke type 1A adolescent idiopathic scoliosis were included in this study. Curve type was further categorized into L4-left (L4-L) or L4-right (L4-R), based on the direction of the L4 vertebral tilt. Several clinical and radiological parameters including sacral slanting were investigated to identify risk factors associated with postoperative distal adding-on. RESULTS: A total of 36 patients (28.6%) exhibited sacral slanting. Nineteen out of 20 L4-L type patients had left-sided sacral slanting, whereas 12 out of 16 L4-R type patients had right-sided sacral slanting. The group with adding-on (n = 13) demonstrated a significantly lower age than the group without adding-on (n = 113). Preoperative lumbar Cobb angle (P = 0.022) was determined to be an independent factor for adding-on according to logistic regression analysis. In the L4-R type, the last touching vertebra (LTV) level and the gap difference in levels between lowest instrumented vertebra and LTV (lowest instrumented vertebra-LTV) comprised significant variables. CONCLUSION: Sacral slanting typically occurs to the left in the L4-L type and to the right in the L4-R type. The size of the preoperative lumbar curve was found to be an independent risk factor that caused adding-on in patients with Lenke type 1A scoliosis. In the L4-R type, right-sided sacral slanting tended to lower the LTV. Therefore, the fusion level might be shorter to save the motion segments resulting in distal adding-on. LEVEL OF EVIDENCE: 4.

Preoperative Magnetic Resonance Imaging Evaluation in Patients with Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective case series. PURPOSE: The purpose of this study was to examine the incidence of neural axis abnormalities and the relevant risk factors in patients with adolescent idiopathic scoliosis (AIS). OVERVIEW OF LITERATURE: The use of preoperative magnetic resonance imaging (MRI) to assess the whole spine in patients with idiopathic scoliosis is controversial, and indications for such MRI evaluations have not been definitively established. However, we routinely use whole-spine MRI in patients with scoliosis who are scheduled to undergo surgical correction. METHODS: A total of 378 consecutive patients with presumed AIS who were admitted for spinal surgery were examined for neural axis abnormalities using MRI. To differentiate patients with normal and abnormal MRI findings, the following clinical parameters were evaluated: age, sex, menarcheal status, rotation angle (using a scoliometer), coronal balance, shoulder height difference, and low back pain. We radiographically evaluated curve type, thoracic or thoracolumbar curve direction, curve magnitude and flexibility, apical vertebral rotation, curve length, coronal balance, sagittal balance, shoulder height difference, thoracic kyphosis, and the Risser sign. RESULTS: Neural axis abnormalities were detected in 24 patients (6.3%). Abnormal MRI findings were significantly more common in males than in females and were associated with increased thoracic kyphosis. However, there were no significant differences in terms of the other measured parameters. CONCLUSIONS: Among the patients with presumed AIS who received preoperative whole-spine MRI, 6.3% had neural axis abnormalities. Males and patients with increased thoracic kyphosis were at a higher risk.

The Relationship between Body Mass Index and Smoking Cessation Plans in Korean Adults.

BACKGROUND: Concerns regarding weight gain after smoking cessation may interfere with quitting smoking. This study investigated the association between smoking cessation plans and body mass index (BMI, kg/m2) in Korean adult smokers. METHODS: Using data from the sixth Korea National Health and Nutrition Examination Survey (2013-2015), 3,000 current smokers aged 19 years or older were selected and divided into four weight groups. The cohorts included an underweight group (BMI, <18.5 kg/m2), normal weight group (BMI, ≥18.5 to <23 kg/m2), overweight group (BMI, ≥23 to <25 kg/m2), and obese group (BMI, ≥25 kg/m2). The relationship between BMI and smoking cessation plans in Korean adults was analyzed using multiple logistic regression analysis. RESULTS: Multiple logistic regression analysis showed sex (odds ratio [OR], 0.723; 95% confidence interval [CI], 0.556-0.939), high-risk drinking (OR, 0.796; 95% CI, 0.634-0.998), aerobic physical activity (OR, 1.326; 95% CI, 1.092-1.612), and hypertension (OR, 1.387; 95% CI, 1.034-1.860) were the significant factors related to smoking cessation plans. According to the BMI categories, the ORs of smoking cessation plans were numerically higher in the normal weight group than the other three groups. However, the difference was not statistically significant. CONCLUSION: Normal weight subjects tended to have a greater number of smoking cessation plans than the other three weight groups, but the difference was not statistically significant. In the clinic, it is necessary to consider not only BMI but also other factors associated with a smoking cessation plans.

Anti-proliferative effects of ginsenosides extracted from mountain ginseng on lung cancer.

OBJECTIVE: To investigate the effect of three major ginsenosides from mountain ginseng as anticancer substance and explore the underlying mechanism involved in lung cancer. METHODS: The inhibitory proliferation of lung cancer by major five ginsenosides (Rb1, Rb2, Rg1, Rc, and Re) was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Calculated 50% inhibition (IC50) values of five ginsenosides were determined and compared each other. Apoptosis by the treatment of single ginsenoside was performed by fluorescence-assisted cytometric spectroscopy. The alterations of apoptosis-related proteins were evaluated by Western blot analysis. RESULTS: The abundance of ginsenosides in butanol extract of mountain ginseng (BX-MG) was revealed in the order of Rb1, Rg1, Re, Rc and Rb2. Among them, Rb1 was the most effective to lung cancer cell, followed by Rb2 and Rg1 on the basis of relative IC50 values of IMR90 versus A549 cell. The alterations of apoptotic proteins were confirmed in lung cancer A549 cells according to the administration of Rb1, Rb2 and Rg1. The expression levels of caspase-3 and caspase-8 were increased upon the treatment of three ginsenosides, however, the levels of caspase-9 and anti-apoptotic protein Bax were not changed. CONCLUSION: Major ginsenosides such as Rb1, Rb2 and Rg1 comprising BX-MG induced apoptosis in lung cancer cells via extrinsic apoptotic pathway rather than intrinsic mitochondrial pathway.

An enzymatically fortified ginseng extract inhibits proliferation and induces apoptosis of KATO3 human gastric cancer cells via modulation of Bax, mTOR, PKB and IκBα.

Accumulative evidence suggests ginseng extract and/or its major components, ginsenosides and compound K, a metabolized ginseng saponin, have anti-cancer effects. In the present study, the effects of a ginseng butanolic extract (GBX) and an enzymatically fortified ginseng extract (FGX), with enriched ginsenosides and compound K, on the growth of KATO3 human gastric cancer cells were investigated using a cell viability assay. While treatment with GBX at 31.25-125 mg/ml for 24 h did not affect the proliferation of KATO3 cells, FGX under the same conditions inhibited cell proliferation in a concentration-dependent manner. Furthermore, Annexin V/PI-staining and flow cytometric analysis demonstrated that the population of apoptotic KATO3 cells was increased following treatment with FGX, which was greater than in the GBX-treated cells, suggesting that FGX had a stronger apoptotic effect than GBX. To investigate the underlying mechanism of the cytostatic and cytotoxic effects of the ginseng extracts, apoptosis-associated proteins were assessed using western blot analysis. The data revealed higher expression levels of B-cell lymphoma 2-associated X protein (Bax), lower expression of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor α (IκBα) and reduced phosphorylation of mammalian target of rapamycin (mTOR) and protein kinase B (PKB) in the FGX-treated KATO3 cells than in the GBX-treated cells. Collectively, these results demonstrated for the first time, to the best of our knowledge, that FGX had stronger anti-proliferative and pro-apoptotic effects on KATO3 cells than GBX. The anti-proliferative and/or pro-apoptotic effects of FGX appeared to be mediated via the upregulation of Bax, IκBα proteolysis (activation of nuclear factor-κB) and the blocking of mTOR and PKB signals.

Feasibility of correction with instrumentation only in congenital scoliosis.

BACKGROUND: Although effective correction of deformity in congenital scoliosis can often be achieved with instrumentation only and without more invasive techniques such as hemivertebrectomy (HV), reports of the feasibility of correction with instrumentation only (IO) are lacking. OBJECTIVE: To compare the results of deformity correction using IO vs HV and to examine the feasibility of and indications for correction with IO in patients with congenital scoliosis. METHODS: Twenty-five patients underwent correction with either IO (n = 14) or HV (n = 11). The 2 patient groups were compared in terms of age at the time of surgery, preoperative magnitude and flexibility of the main curve, correction rates after surgery and at the final follow-up, surgery time, estimated blood loss, and complications. RESULTS: The 2 groups did not differ significantly in terms of average patient age or curve magnitude, but the correction with the IO group had greater preoperative curve flexibility (37.1%) than the HV group (21.0%). The correction rates immediately after surgery were high in both groups. The correction with IO group had a shorter mean operation time (308 minutes vs 366 minutes) and less blood loss (540 mL vs 1547 mL) than the HV group. CONCLUSION: Satisfactory correction of congenital scoliosis can be obtained with IO if there is adequate flexibility in the main curve, thus avoiding the need for more invasive procedures such as HV.

Inhibition of tumor growth and histopathological changes following treatment with a chemokine receptor CXCR4 antagonist in a prostate cancer xenograft model.

The stromal derived factor-1 (SDF-1)/CXCR4 axis is associated with tumor aggressiveness and metastasis in prostate cancer. The present study aimed to explore the potential therapeutic effects of a CXCR4 antagonist in prostate cancer. The effect of SDF-1 and a CXCR4-specific antagonist, AMD3100, on human prostate cancer PC-3 cell proliferation and protein kinase B (Akt) signaling was assessed. Moreover, a PC-3 tumor xenograft model was used to evaluate the effect of AMD3100 on tumor growth and to identify the histopathological changes and immunohistochemical differences between AMD3100-treated and untreated groups. Cell proliferation was not significantly affected by SDF-1 or AMD3100 treatment in vitro. Western blot analysis revealed that SDF-1 stimulation enhanced the expression of phosphorylated Akt in the PC-3 cells, but that the SDF-1-induced expression of phosphorylated Akt was abrogated in the AMD3100-treated PC-3 cells. In the PC-3 tumor xenograft model, AMD3100 significantly inhibited tumor growth, while AMD3100-treated PC-3 tumors had lower levels of microvessel formation and a lower immunoreactivity for the proliferation marker Ki-67 and the anti-apoptotic marker Bcl-2 compared to control tumors in vivo. The CXCR4-specific antagonist inhibits SDF-1-induced CXCR4/Akt signal transduction, and effectively suppresses tumor growth in the PC-3 xenograft model. The present study indicates that CXCR4 targeting may represent a novel strategy for the treatment of castration-resistant prostate cancer (CRPC).

Effectiveness of the Charleston night-time bending brace in the treatment of adolescent idiopathic scoliosis.

BACKGROUND: Part-time or night-time bracing has been introduced to address the poor compliance and psychological burden of full-time bracing. The results of various bracing methods vary, however, due to a lack of consistent inclusion criteria and definitions of brace effectiveness. We have evaluated the effectiveness of the Charleston night-time bending brace in the treatment of adolescent idiopathic scoliosis based on the new standardized criteria proposed by the Scoliosis Research Society. METHODS: To be included in this study, patients met the following criteria proposed by the Scoliosis Research Society: diagnosis of adolescent idiopathic scoliosis, age 10 years and older when the orthosis was prescribed, Risser 0-2, a primary curve magnitude of 25 to 40 degrees, and no prior treatment. A total of 95 patients (87 girls, 8 boys) were included. RESULTS: At skeletal maturity, 80 patients (84.2%) had 5 degrees or less curve progression and 15 (15.8%) had 6 degrees or more progression. Seven patients (7.8%) were recommended to undergo or underwent surgery before skeletal maturity. Eleven patients (12.6%) progressed beyond 45 degrees. According to these 3 criteria, the Charleston night-time brace was successful in 74 patients (77.9%). Depending on curve type, we observed success rates of 78.3% (47/60) for double, 71.4% (15/21) for thoracic, 83.3% (5/6) for thoracolumbar, and 87.5% (7/8) for lumbar curves. Success rates of 80.0% (36/45) and 76.0% (38/50) were observed in patients with curve magnitudes at bracing of 25 to 30 degrees and 31 to 40 degrees, respectively. Patients with high apex curves had a 67.6% (23/34) success rate, and those with low apex curves had 83.0% (39/47) success rate. Brace success rates among patients with initial Risser signs of 0, 1, and 2 were 68.8% (22/32), 80.6% (25/31), and 84.4% (27/32), respectively. CONCLUSIONS: Compared with the results of previous natural history and conventional brace study, the Charleston night-time bending brace is effective for the treatment of adolescent idiopathic scoliosis. LEVEL OF EVIDENCE: Level VI.

Lipid raft cholesterol and genistein inhibit the cell viability of prostate cancer cells via the partial contribution of EGFR-Akt/p70S6k pathway and down-regulation of androgen receptor.

Soy isoflavones and cholesterol have been reported as dietary factors related to the incidence of prostate cancer. In this study, we investigated whether cell survival could be suppressed by a combination of the dispersion of lipid raft microdomains and treatment with genistein, a well-known potential isoflavone, in LNCaP prostate cancer cells. Cell viability was assayed by the property of reagent change upon reduction of resazurin to resorufin and apoptosis was evaluated by ethidium bromide/acridine orange (EB/AO) staining and PARP and caspase-3 expression. Signal transduction was investigated by immunoblot analysis. Cell viability decreased significantly more following successive double treatment with genistein and the cholesterol-lowering agent 2-hydroxypropyl-beta-cyclodextrin (HPCD) than in response to either agent alone. Apoptotic cell staining and cleavage of PARP and caspase-3 appeared more clearly in double-treated cells than in those treated with genistein alone. In cell signaling, both HPCD and genistein decreased the protein expressions of pAkt as well as the androgen receptors stimulated by EGF and DHT, respectively, in concentration-dependent manners. This pattern was also present in protein levels of pAkt and the androgen receptor located in the lipid raft fraction. Furthermore, the phosphorylation cascade of Akt, GSK-3beta and p70S6k was markedly inhibited by the combination treatment. These data suggest that prostate cancer cells could be effectively inhibited by combination treatment of cholesterol-lowering strategies and genistein. The mechanism is likely to be partially via both the EGFR-mediated Akt or p70S6k pathways and a down-regulation of androgen receptor in the lipid raft microdomain.

Preventive effects of oligomerized polyphenol on estradiol-induced prostatitis in rats.

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS, NIH category III) accounts for 90-95% of prostatitis cases. However, standard treatment has not yet been established. It is known that polyphenols have an inhibitory effect on inflammation by their antioxidative capacity, and oligonol, a polyphenol derivative, has much higher bioavailability and bioactivity than common polyphenols. We investigated the anti-inflammatory effects and mechanisms of oligonol in estradiol-induced prostatitis rat models. MATERIALS AND METHODS: Prostatitis was induced by 17 beta-estradiol (E2) and dihydrotestosterone (DHT) in Wistar male rats (n = 20). Ten rats were placed in the oligonol-treated group and 10 in the E2 + DHT-treated group. The other 10 rats were also included as normal control group. Oligonol (60 mg/kg/day) was administered via gavage tube for 4 weeks. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and tumor necrosis factor-alpha (TNF-alpha) were quantified, and phosphorylation of IkappaBa and histological changes were also evaluated in prostatic tissue. RESULTS: The SOD and GPx activity showed tendencies to increase in the oligonol-treated group compared to the normal control group. TNF-alpha expression was slightly reduced in the oligonol-treated group. Western blotting demonstrated that phosphorylation of IkappaBa in the oligonol-treated group was significantly lower than in the normal control group. The E2 + DHT-treated group revealed severe atrophy of acinar epithelial cells and infiltration of leukocytes and lymphocytes in the prostate, however, the oligonol-treated group showed overall reduction in inflammatory features. CONCLUSION: This study demonstrates that oligonol improves estradiol-induced non-bacterial prostatitis by regulating phosphorylation of IkappaBa. These findings suggest that oligonol has a beneficial effect on prevention and treatment of CP/CPPS.