Risk factors for proximal junctional kyphosis after posterior long-segment internal fixation for chronic symptomatic osteoporotic thoracolumbar fractures with kyphosis.

BACKGROUND: This study aimed to analyze the risk factors for proximal junctional kyphosis (PJK) for patients with chronic symptomatic osteoporotic thoracolumbar fractures (CSOTLF) and kyphosis who underwent long-segment internal fixation. METHODS: We retrospectively reviewed the records of patients with CSOTLF complicated with kyphosis who underwent posterior multilevel internal fixation in our hospital between January 2013 and January 2020. The patients' age, sex, body mass index (BMI), bone mineral density (BMD), smoking status, cause of injury, comorbidities, injury segments, and American Spinal Injury Association (ASIA) grading non-surgical data; posterior ligament complex (PLC) injury, upper and lower instrumented vertebral position (UIV and LIV, respectively), number of fixed segments surgical data, proximal junctional angle (PJA), sagittal vertebral axis (SVA), pelvic incidence (PI), lumbar lordosis (LL), pelvic incidence-lumbar lordosis mismatch (PI-LL), pelvic tilt (PT), and sacral slope (SS) surgical indicators were collected. Patients were divided into postoperative PJK and non-PJK groups. RESULTS: This study included 90 patients; among them, 30 (31.58%) developed PJK postoperatively. All patients were followed up for > 24 months (mean 32.5 months). Univariate analysis showed significant differences in age, BMI, BMD, PLC injury, UIV, and LIV fixation position, number of fixation stages, and preoperative PJA, SVA, PI-LL, and SS between the two groups (P < 0.05). Additionally, no significant differences were observed in sex, smoking, cause of injury, complications, injury segment ASIA grade, and preoperative PT between the two groups (P > 0.05). Multifactorial logistic regression analysis showed that age > 70 years (OR = 32.279, P < 0.05), BMI > 28 kg/m2 (OR = 7.876, P < 0.05), BMD T value < - 3.5 SD (OR = 20.836, P < 0.05), PLC injury (OR = 13.981, P < 0.05), and preoperative PI-LL > 20° (OR = 13.301, P < 0.05) were risk factors for PJK after posterior long-segment internal fixation in elderly patients with CSOTLF complicated with kyphosis. CONCLUSION: CSOTLF patients undergoing posterior long segment internal fixation are prone to PJK, and age > 70 years, BMI > 28 kg/m2, BMD T value < - 3.5 SD, preoperative PI-LL > 20° and PLC injury may increase their risk.

Can paraspinal muscle degeneration be a reason for refractures after percutaneous kyphoplasty? A magnetic resonance imaging observation.

BACKGROUND: Vertebral augmentation (VA) techniques are used to treat acute osteoporotic vertebral compression fractures (OVCFs). However, the incidence of recurrent vertebral fractures after VA is controversial. Various factors have been discussed in the literature, but no convincing study on the quality of paraspinal muscles has been reported. The purposes of this study were to evaluate the changes in paraspinal muscles and discuss the relationship between paraspinal muscle degeneration and vertebral refractures after percutaneous kyphoplasty (PKP). METHODS: This retrospective study was conducted in patients who underwent PKP for an initial OVCF between July 2017 and August 2018. Patients were followed up and categorized in the refractured or non-refractured group. A final magnetic resonance imaging (MRI) scan and a preoperative MRI scan were used to determine the measurements. The paraspinal muscles at the mid-height level of the initial fractured vertebral body were measured using regions of interest (ROIs), including the cross-sectional area (CSA) and signal intensity (SI). The changes in the observed data were compared between the groups using rank-sum tests. RESULTS: Overall, 92 patients were enrolled in the study; 33 of them sustained vertebral refractures during the follow-up and the other 59 patients did not. There were no significant differences in terms of sex, age, preoperative bone mineral density, and body mass index between the groups (all, P > 0.05). The refractured group had a significantly higher decrease in the ROI-CSA and CSA/SI, and a higher increase in ROI-SI, compared with the preoperative data (all, P < 0.05). CONCLUSIONS: The quality of paraspinal muscles significantly decreased in patients with new OVCFs after PKP. This brings a new perspective to the study of postoperative recurrent fractures; patients and physicians need to pay more attention to the efficacy of bed rest and bracing.

Can Additional Facet Joint Block Improve the Clinical Outcome of Kyphoplasty for Acute Osteoporotic Vertebral Compression Fractures?

BACKGROUND: Percutaneous kyphoplasty (PKP) has been reported to provide a favorable analgesic effect for pain caused by osteoporotic vertebral compression fractures (OVCFs). However, a systematic review demonstrated that pain relief was only reported for approximately 86% of kyphoplasty treatments. OBJECTIVES: To explore whether an additional facet joint block (FJB) can minimize pain and improve the clinical outcome of PKP in patients with acute OVCFs. STUDY DESIGN: Prospective study. SETTING: All data were from Honghui Hospital in Xi'an. METHODS: According to the inclusion and exclusion criteria, 194 patients were eventually included in our study; they were randomly divided into 2 groups of 97 patients each and treated with either PKP + FJB or PKP alone. Follow-up consultations were scheduled 1 day, 3 days, 1 week, 1 month, 3 months, and 1 year postoperatively; the demographic characteristics, related surgical information, and complications observed within both groups were recorded. The clinical evaluation parameters included the intraoperative satisfaction score, the Visual Analog Scale (VAS) score, and the Oswestry Disability Index (ODI). RESULTS: A total of 171 patients (61 men and 110 women; age range: 62-85 years) completed the full postoperative follow-up schedule, with 83 patients in the PKP + FJB group and 88 in the PKP group. No significant differences were observed in the genders, ages, preoperative bone mineral density, surgical levels, or volume of cement injected between the 2 groups (P > 0.05, respectively). The average duration of the surgeries in the PKP + FJB group was slightly longer than that in the PKP group (35.5 ± 4.8 min vs. 31.8 ± 4.3 min; P = 0.038), and in terms of the clinical outcomes, the average intraoperative satisfaction score was significantly higher in the PKP + FJB group (8.6 ± 1.1 vs. 6.3 ± 1.3; P < 0.001). Compared with the preoperative data, significant improvements in the VAS scores of back pain and ODI were observed at each follow-up interval (P < 0.05, respectively). These scores were significantly higher in the PKP + FJB group than in the PKP group; however, this was only observed within the first month after the procedure. LIMITATIONS: A single-center noncontrol study. CONCLUSIONS: The addition of an FJB (which in our study involved a unique combination of ropivacaine, prednisolone, and vitamin B12) improved the short-term clinical outcome of PKP for acute OVCFs. The local anti-inflammatory and analgesic effects on the facet joints resulted in higher intraoperative satisfaction and lower VAS and ODI scores for the first postoperative month when compared with the PKP group.

When is the circumferential stabilization necessary for subaxial cervical fracture dislocations? The posterior ligament-bone injury classification and severity score: a novel treatment algorithm.

OBJECTIVE: To propose a novel classification and scoring system called the posterior ligament-bone injury classification and severity score (PLICS) that offers a quantitative score to guide the need for posterior stabilization in addition to anterior reconstruction for subaxial cervical fracture dislocations (SCFDs). METHODS: A total of 456 patients with SCFDs were prospectively included. Patients with PLICS ≥ 7 together with extremely unstable lateral mass fracture (EULMF) were classified as high-risk group, and the other patients were classified as low-risk group. For patients in the low-risk group, anterior-only reconstruction was performed; for patients in the high-risk group, additional posterior lateral mass fixation and fusion was performed after anterior reconstruction. Clinical outcome evaluation included using the visual analogue score (VAS), the Neck Disability Index (NDI), and the American Spinal Injury Association (ASIA) impairment scale. The change in the local sagittal alignment kyphosis Cobb angle was also recorded. RESULTS: A total of 370 patients (81.1%) completed the minimal 12-month follow-ups, including 321 patients of low-risk group and 49 patients of high-risk group. Compared with the average VAS score preoperatively, the score at 12-month follow-up was significantly improved (from 6.1 + 0.3 to 1.1 + 0.2 in the low-risk group, P < 0.001; from 6.4 + 0.2 to 1.4 + 0.2 in the high-risk group, P < 0.001). The average NDI score at the 12-month follow-up was statistically low in the low-risk group (8.8 + 2.5 vs 13.8 + 3.4, P = 0.034). At least more than one grade improvement in the ASIA scale was observed in 80.5% of all patients. The local kyphosis Cobb angle at the injured segment averaged improved in both groups. CONCLUSION: A PLICS score ≥ 7 together with EULMF can be the threshold for posterior stabilization in addition to anterior reconstruction for the patients with SCFDs.

Comparison of Clinical and Radiologic Outcome Between Mini-Open Wiltse Approach and Fluoroscopic-Guided Percutaneous Pedicle Screw Placement: A Randomized Controlled Trial.

OBJECTIVE: To compare clinical efficacy, radiographic outcome, and radiation exposure between mini-open pedicle screw (MPS) fixation with the Wiltse approach and percutaneous pedicle screw (PPS) fixation in treatment of young and middle-aged patients with thoracolumbar burst fractures. METHODS: Of 60 patients with thoracolumbar vertebrae fractures treated in our hospital from January 2017 to January 2018, 30 were randomly assigned to the MPS group and 30 were randomly assigned to the PPS group. Clinical efficacy, radiographic outcome, and radiation exposure were compared between the 2 groups. RESULTS: The average age of patients was 42.2 ± 6.7 years in the MPS group and 43.0 ± 6.9 years in the PPS group (P = 0.668). There was no significant difference between the 2 groups in blood loss, hospital stay, postoperative visual analog scale score for back pain, and Oswestry Disability Index score. The vertebral body height and vertebral body angle of the MPS group were significantly better than those of the PPS group at the last follow-up. There was no significant difference in the accuracy rate of pedicle screw placement between the MPS group and the PPS group; the facet joint violation was significantly higher in the PPS group. The average radiation exposure dosage was lower in the MPS group. CONCLUSIONS: Both MPS fixation with the Wiltse approach and PPS fixation are safe and effective in the treatment of single-segment thoracolumbar vertebral fractures. Nevertheless, considering the surgical duration, radiation exposure, facet joint violation, vertebral body height, and vertebral body angle at the last follow-up, MPS fixation with the Wiltse approach is a better choice than PPS.

The novel lncRNA p4516 acts as a prognostic biomarker promoting gastric cancer cell proliferation and metastasis.

Purpose: Emerging evidence has shown that long noncoding RNAs (lncRNAs) participate in oncogenesis and tumor progression. We previously found a novel lncRNA p4516 which was closely associated with prognosis by preliminary study of lncRNA expression profile from paired tumors and nontumor tissues in 198 gastric cancer (GC) patients. However, the exact biological functions and the underlying molecular mechanisms of p4516 in gastric tumorigenesis still remain unclear. Materials and methods: The RNA fluorescence in situ hybridization (RNA-FISH) analysis, cytoplasmic and nuclear RNA isolation and qRT-PCR were applied to determine the subcellular localization of p4516. Expression levels of p4516 were assessed using qRT-PCR in both GC cell lines and in 142 primary GC tissues. Correlations between p4516 expression and GC patients' clinicopathological parameters were analyzed. Gain- and loss-of-function experiments were employed to investigate the role of p4516 in proliferation, migration and invasion both in vitro and in vivo. In addition, Western blotting and immunohistochemical staining were used to examine the protein expression levels. Results: LncRNA p4516 was mainly localized in the nucleus of GC cells and p4516 tended to have higher expression levels in GC cells compared to the normal gastric mucosa-derived cells GES-1. Furthermore, higher expression levels of p4516 correlated with worse clinical outcomes in GC patients and acted as an independent prognostic biomarker. Functional analysis revealed that p4516 participated in the regulation of GC cell proliferation, invasion and migration both in vivo and in vitro. Moreover, p4516 was involved in epithelial-mesenchymal transition (EMT) in GC cells. Conclusion: Our study demonstrated the oncogenic role of novel lncRNA p4516 in the gastric carcinogenesis for the first time. High expression of p4516 may act as prognostic marker in patient with gastric cancer.

ISL1 predicts poor outcomes for patients with gastric cancer and drives tumor progression through binding to the ZEB1 promoter together with SETD7.

ISL1, a LIM-homeodomain transcription factor, serves as a biomarker of metastasis in multiple tumors. However, the function and underlying mechanisms of ISL1 in gastric cancer (GC) have not been fully elucidated. Here we found that ISL1 was frequently overexpressed in GC FFPE samples (104/196, 53.06%), and associated with worse clinical outcomes. Furthermore, the overexpression of ISL1 and loss-of-function of ISL1 influenced cell proliferation, invasion and migration in vitro and in vivo, including GC patient-derived xenograft models. We used ChIP-seq and RNA-seq to identify that ISL1 influenced the regulation of H3K4 methylation and bound to ZEB1, a key regulator of the epithelial-mesenchymal transition (EMT). Meanwhile, we validated ISL1 as activating ZEB1 promoter through influencing H3K4me3. We confirmed that a complex between ISL1 and SETD7 (a histone H3K4-specific methyltransferase) can directly bind to the ZEB1 promoter to activate its expression in GC cells by immunoprecipitation, mass spectrometry, and ChIP-re-ChIP. Moreover, ZEB1 expression was significantly positively correlated with ISL1 and was positively associated with a worse outcome in primary GC specimens. Our paper uncovers a molecular mechanism of ISL1 promoting metastasis of GC through binding to the ZEB1 promoter together with co-factor SETD7. ISL1 might be a potential prognostic biomarker of GC.

High-level SAE2 promotes malignant phenotype and predicts outcome in gastric cancer.

BACKGROUND: The SUMO pathway has been shown to play an important role in tumorigenesis. This report analyzed the involvement of the sole SUMO-Activating Enzyme Subunit 2 (SAE2) in human gastric cancer (GC) progression and prognosis. METHODS: Expression of SAE2 was examined by Quantigene Plex, western blotting and immunohistochemistry. The expression of SAE2 and c-MYC were detected in parallel in 276 cases. The molecular mechanisms of SAE2 expression and its effects on cell growth, colony formation, migration and invasion were also explored by CCK8 assay, colony formation experiment, transwell chamber assay with or without matrigel, immunoprecipitation and in vivo tumorigenesis and tumor metastasis. RESULTS: SAE2 was markedly overexpressed in GC cell lines and primary tumor samples of GC, and significantly correlated with deeper tumor depth, distant metastasis, higher pathological stage and stratified survival in human GC. SAE2 positivity was independently associated with a worse outcome in multivariate analysis. Knockdown of SAE2 expression inhibited the proliferation, migration, and invasion of SAE2-overexpressing GC cells. Consistent with the in vitro results, down-regulation of SAE2 in human GC BGC823 cells significantly reduced the tumorigenic and metastatic potential of the cells in vivo. SAE2 protein was significantly associated with the higher expression of c-MYC in primary GC tissues. Moreover, FoxM1 was SUMOylated in GC and that inhibition of SAE2 resulted in a decrease in SUMO1-FoxM1 levels compared with those in the controls. CONCLUSIONS: These findings suggest that SAE2 has a pivotal role in the aggressiveness of GC, and highlight its usefulness as a prognostic factor in GC.

High-level SAE2 promotes malignant phenotype and predicts outcome in gastric cancer.

BACKGROUND: The SUMO pathway has been shown to play an important role in tumorigenesis. This report analyzed the involvement of the sole SUMO-Activating Enzyme Subunit 2 (SAE2) in human gastric cancer (GC) progression and prognosis. METHODS: Expression of SAE2 was examined by Quantigene Plex, western blotting and immunohistochemistry. The expression of SAE2 and c-MYC were detected in parallel in 276 cases. The molecular mechanisms of SAE2 expression and its effects on cell growth, colony formation, migration and invasion were also explored by CCK8 assay, colony formation experiment, transwell chamber assay with or without matrigel, immunoprecipitation and in vivo tumorigenesis and tumor metastasis. RESULTS: SAE2 was markedly overexpressed in GC cell lines and primary tumor samples of GC, and significantly correlated with deeper tumor depth, distant metastasis, higher pathological stage and stratified survival in human GC. SAE2 positivity was independently associated with a worse outcome in multivariate analysis. Knockdown of SAE2 expression inhibited the proliferation, migration, and invasion of SAE2-overexpressing GC cells. Consistent with the in vitro results, down-regulation of SAE2 in human GC BGC823 cells significantly reduced the tumorigenic and metastatic potential of the cells in vivo. SAE2 protein was significantly associated with the higher expression of c-MYC in primary GC tissues. Moreover, FoxM1 was SUMOylated in GC and that inhibition of SAE2 resulted in a decrease in SUMO1-FoxM1 levels compared with those in the controls. CONCLUSIONS: These findings suggest that SAE2 has a pivotal role in the aggressiveness of GC, and highlight its usefulness as a prognostic factor in GC.

Smoking and air pollution exposure and lung cancer mortality in Zhaoyuan County.

BACKGROUND: Simultaneous exposure to high levels of air pollution and high tobacco consumption at the same place is rare. The aim of the present study was to evaluate the impact of the two factors on the risk of developing lung cancer. METHODS: Data on the number of deaths due to lung cancer and on population from 1970 to 2009 were obtained from Zhaoyuan County. Data on the smoking populations were obtained at random sampling survey during the time in Zhaoyuan. Data on the components of atmospheric surveillance were obtained from the local environmental protection offices. Logarithmic linear regression and general log-linear Poisson age-period-cohort (APC) models were used to estimate age, period, cohort, gender, smoking, and air pollution effects on the risk of lung cancer mortality. RESULTS: The standardized mortality rates of lung cancer drastically increased from 8.43 in per 100 000 individuals in the 1970-1974 to 25.67 in per 100 000 individuals in the 2005-2009 death survey. The annual change of lung cancer mortality was 3.20%. In the log linear regression model, the age, proportion of smokers, gender, period, and air pollution are significantly associated with lung cancer mortality. The APC analysis shows that the relative risks (RRs) of gender, smoking, and air pollution are 2.29 (95% confidence interval (CI): 2.16-2.43), 3.05 (95% CI = 2.76-3.36), and 1.42 (95% CI = 1.19-1.69), respectively. Compared with the period 1970-1974, high RRs were found during 1995-2009. Compared with the birth cohort 1950-1954, the RRs increased in the birth cohorts of 1910 to the 1940. Compared the aged 35-59 and 60-84 in the 1980-1984 death survey (not exposed to air pollution) with that in the 2005-2009 death survey (exposed to air pollution), The two age groups exposed to air pollution, 25 years later, had an increased mortality rates for lung cancer by 2.27 and 3.55 times for males and by 1.47 and 3.35 times for females. CONCLUSION: The mortality rates of lung cancer drastically increased in the past 35 years. The trend of lung cancer mortality may be in a great extent possibly due to the effects of combined smoking and air pollution exposure.

Nutrition deficiency increases the risk of stomach cancer mortality.

BACKGROUND: The purpose of the study is to determine whether exposure to malnutrition during early life is associated with increased risk of stomach cancer in later life. METHODS: The design protocol included analyzing the trend of gastric cancer mortality and nutrition and evaluating the association between nutrient deficiency in early life and the risk of gastric cancer by hierarchical age-period-birth cohort (APC) analysis using general log-linear Poisson models and to compare the difference between birth cohorts who were exposed to the 1959-1961 Chinese famine and those who were not exposed to the famine. Data on stomach cancer mortality from 1970 to 2009 and the dietary patterns from 1955 to 1985 which included the 1959-1961 Chinese famine period in the Zhaoyuan County population were obtained. The nutrition information was collected 15 years prior to the mortality data as based on the latest reference of disease incubation. RESULTS: APC analysis revealed that severe nutrition deficiency during early life may increase the risk of stomach cancer. Compared with the 1960-1964 birth cohort, the risk for stomach cancer in all birth cohorts from 1900 to 1959 significantly increased; compared with the 1970-1974 cohort, the risk for stomach cancer in the 1975-1979 cohort significantly increased, whereas the others had a steadily decreased risk; compared with 85-89 age group in the 2005-2009 death survey, the ORs decreased with younger age and reached significant levels for the 50-54 age group after adjusting the confounding factors. The 1930 to 1964 group (exposed to famine) had a higher mortality rate than the 1965 to 1999 group (not exposed to famine). For males, the relative risk (RR) was 2.39 and the 95% confidence interval (CI) was 1.51 to 3.77. For females, RR was 1.64 and 95% CI was 1.02 to 2.62. CONCLUSION: The results of the present study suggested that prolonged malnutrition during early life may increase the risk of stomach cancer mortality in later life.

Multi-susceptibility genes associated with the risk of the development stages of esophageal squamous cell cancer in Feicheng County.

BACKGROUND: The purpose of this study was to evaluate the association of multi-genotype polymorphisms with the stepwise progression of esophageal squamous cell cancer (ESCC) and the possibility of predicting those at higher risk. METHODS: A total of 1,004 subjects were recruited from Feicheng County, China, between Jan. 2004 and Dec. 2007 and examined by endoscopy for esophageal lesions. These subjects included 270 patients with basal cell hyperplasia (BCH), 262 patients with esophageal squamous cell dysplasia (ESCD), 226 patients with ESCC, and 246 controls with Lugol-voiding area but diagnosed as having normal esophageal squamous epithelial cells by histopathology. The genotypes for CYP2E1 G1259C, hOGG1 C326G, MTHFR C677T, MPO G463A, and ALDH2 allele genes were identified in blood samples collected from all participants. RESULTS: The alleles ALDH2 and MTHFR C677T were critical for determining individual susceptibility to esophageal cancer. Compared to the ALDH 1*1 genotype, the ALDH 2*2 genotype was significantly associated with increased risks of BCH, ESCD, and ESCC. However, the TT genotype of MTHFR C677T only increased the risk of ESCC. Further analysis revealed that the combination of the high-risk genotypes 2*2/1*2 of ALDH 2 and TT/TC of MTHFR C677T increased the risk of BCH by 4.0 fold, of ESCD by 3.7 fold, and ESSC by 8.72 fold. The generalized odds ratio (ORG) of the two combined genotypes was 1.83 (95%CI: 1.55-2.16), indicating a strong genetic association with the risk of carcinogenic progression in the esophagus. CONCLUSIONS: The study demonstrated that the genotypes ALDH2*2 and MTHFR 677TT conferred elevated risk for developing esophageal carcinoma and that the two susceptibility genotypes combined to synergistically increase the risk.