Lumbar Apex Position as an Independent Risk Factor for Adjacent Segment Diseases in Patients Undergoing Short-level Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective study. OBJECTIVE: To investigate whether lumbar apex position had an impact on the development of adjacent segment disease (ASD) following transforaminal lumbar interbody fusion (TLIF). SUMMARY OF BACKGROUND DATA: Previous studies have demonstrated that solely concentrating on lumbar lordosis value is not suitable and neglecting the significance of lumbar apex can lead to mechanical complications. However, the relationship between lumbar apex and ASD is still not well understood. METHODS: In this retrospective study, 234 consecutive patients who underwent L3-5 or L4-5 TLIF for degenerative diseases were reviewed. The study evaluated the associations between sagittal parameters and pelvic incidence (PI). Patients were labeled "matched" when lumbar apex position aligned with the theoretical target, and "mismatched" when it did not. Multivariate analysis was applied to find the independent risk factors of ASD. Additionally, a focused sub-analysis was performed based on the lumbar apex position (ideal match, cranial from ideal, and caudal from ideal). RESULTS: After an average follow-up period of 70.6 months, 68 cases were identified as having ASD. Postoperatively, 64.7% (44 out of 68) of the patients with ASD exhibited a mismatched lumbar apex, compared to 41% (68 out of 166) of those without ASD (p < 0.001). PI correlated significantly with proximal lordosis (PL) and lordosis distribution index (LDI), but not with distal lordosis (DL). Multivariate analysis identified age, L3-5 fusion, postoperative DL, and postoperative mismatched lumbar apex as independent risk factors of ASD. Upon the sub-analysis, it was discovered that there were unique compensatory strategies in the cranial and caudal groups, with notable variations in postoperative DL, PL, and LDI among three groups (all p value<0.05). CONCLUSION: Lumbar apex position significantly influenced the risk of ASD. To restore the lumbar apex to its ideal position, a proper value and distribution of DL should be attained.

Validation of Roussouly classification in predicting the occurrence of adjacent segment disease after short-level lumbar fusion surgery.

BACKGROUND: Recent studies demonstrated that restoring sagittal alignment to the original Roussouly type can remarkably reduce complication rates after adult spinal deformity surgery. However, there is still no data proving the benefit of maintaining ideal Roussouly shape in the lumbar degenerative diseases and its association with the development of adjacent segment disease (ASD). Thus, this study was performed to validate the usefulness of Roussouly classification to predict the occurrence of ASD after lumbar fusion surgery. MATERIALS AND METHODS: This study retrospectively reviewed 234 consecutive patients with lumbar degenerative diseases who underwent 1- or 2-level fusion surgery. Demographic and radiographic data were compared between ASD and non-ASD groups. The patients were classified by both "theoretical" [based on pelvic incidence (PI)] and "current" (based on sacral slope) Roussouly types. The patients were defined as "matched" if their "current" shapes matched the "theoretical" types and otherwise as "mismatched". The logistic regression analysis was performed to identify the factors associated with ASD. Finally, clinical data and spinopelvic parameters of "theoretical" and "current" types were compared. RESULTS: With a mean follow-up duration of 70.6 months, evidence of ASD was found in the 68 cases. Postoperatively, ASD group had more "current" shapes classified as type 1 or 2 and fewer as type 3 than the non-ASD group (p < 0.001), but the distribution of "theoretical" types was similar between groups. Moreover, 80.9% (55/68) of patients with ASD were mismatched, while 48.2% (80/166) of patients without ASD were mismatched (p < 0.001). A multivariate analysis identified age [odds ratio (OR) = 1.058)], 2-level fusion (OR = 2.9830), postoperative distal lordosis (DL, OR = 0.949) and mismatched Roussouly type (OR = 4.629) as independent risk factors of ASD. Among the four "theoretical" types, type 2 had the lowest lumbar lordosis, DL, and segmental lordosis. When considering the "current" types, current type 2 was associated with higher rates of 2-level fusion, worse DL, and greater pelvic tilt compared with other current types. CONCLUSIONS: DL loss and mismatched Roussouly type were significant risk factors of ASD. To decrease the incidence of ASD, an appropriate value of DL should be achieved to restore sagittal alignment back to the ideal Roussouly type. LEVEL OF EVIDENCE: Level 4.

Validation of age-adjusted pelvic incidence minus lumbar lordosis and lordosis distribution index for assessing adjacent-segment disease after short-level lumbar fusion surgery: minimum 5 years of follow-up.

OBJECTIVE: The purpose of this study was to investigate the influence of sagittal alignment according to age-adjusted pelvic incidence minus lumbar lordosis (PI-LL) and lordosis distribution index (LDI) on the occurrence of adjacent-segment disease (ASD) after lumbar fusion surgery. METHODS: This study retrospectively reviewed 234 consecutive patients with lumbar degenerative diseases who underwent 1- or 2-level lumbar fusion surgery. Demographic and radiographic (preoperative and 3-month postoperative) data were collected and compared between ASD and non-ASD groups. Binary logistic regression analysis was performed to evaluate adjusted associations between potential variables and ASD development. A subanalysis was further conducted to assess their relationships in the range of different PI values. RESULTS: With a mean follow-up duration of 70.6 months (range 60-121 months), 118 patients (50.4%) were diagnosed as having cranial radiological ASD. Univariate analyses showed that older age, 2-level fusion, worse preoperative pelvic tilt and LL, lower pre- and postoperative LDI, and more improvement in sagittal vertical axis were significantly correlated with the occurrence of ASD. No significant differences in the PI-LL and age-adjusted PI-LL (offset) were detected between ASD and non-ASD groups. Multivariate analysis identified postoperative LDI (OR 0.971, 95% CI 0.953-0.989, p = 0.002); 2-level fusion (OR 3.477, 95% CI 1.964-6.157, p < 0.001); and improvement of sagittal vertical axis (OR 0.992, 95% CI 0.985-0.998, p = 0.039) as the independent variables for predicting the occurrence of ASD. When stratified by PI, LDI was identified as an independent risk factor in the groups with low and average PI. Lower segmental lordosis (OR 0.841, 95% CI 0.742-0.954, p = 0.007) could significantly increase the incidence of ASD in the patients with high LDI. CONCLUSIONS: Age-adjusted PI-LL may have limited ability to predict the development of ASD. LDI could exert an important effect on diagnosing the occurrence of ASD in the cases with low and average PI, but segmental lordosis was a more significant risk factor than LDI in individuals with high PI.

MicroRNA-324-3p inhibits osteosarcoma progression by suppressing PGAM1-mediated aerobic glycolysis.

Osteosarcoma (OS) is the most common primary malignant neoplasm of the bone. Recent studies have indicated that the inhibitory effects of microRNA (miR)-324-3p could affect the development of numerous cancers. However, its biological roles and underlying mechanisms in OS progression remain unexplored. In this study, miR-324-3p expression was markedly reduced in OS cell lines and tissues. Functionally, miR-324-3p overexpression suppressed OS progression and was involved in the Warburg effect. Mechanistically, miR-324-3p negatively regulated phosphoglycerate mutase 1 (PGAM1) expression by targeting its 3'-UTR. Moreover, high expression of PGAM1 promoted OS progression and aerobic glycolysis, which were associated with inferior overall survival in patients with OS. Notably, the tumor suppressor functions of miR-324-3p were partially recovered by PGAM1 overexpression. In summary, the miR-324-3p/PGAM1 axis plays an important role in regulating OS progression by controlling the Warburg effect. Our results provide mechanistic insights into the function of miR-324-3p in glucose metabolism and subsequently on the progression of OS. Targeting the miR-324-3p/PGAM1 axis could be a promising molecular strategy for the treatment of OS.

Unmatched rod contouring at the proximal end predisposes to occurrence of junctional kyphosis in early-onset scoliosis patients undergoing traditional growing rods treatment.

STUDY DESIGN: A retrospective case series. OBJECTIVE: To investigate whether unmatched rod contouring at the proximal end predisposed to the occurrence of proximal junctional kyphosis (PJK) in early-onset scoliosis (EOS) patients after traditional growing rods (TGR) treatment. TGR treatment has become a mainstay of treatment for EOS patients. PJK is one of the most common alignment-related complications. METHODS: A consecutive series of EOS patients who had undergone TGR treatment were retrospectively reviewed. They were divided into PJK and non-PJK groups according to the occurrence of PJK or not. Demographic data, surgical strategies, and radiographic parameters were recorded and compared between groups. Proximal junctional angle (PJA) was defined as the angle between the caudal endplate of the UIV and the cephalad endplate of the second supradjacent vertebra above the UIV, while proximal rod contouring angle (PRCA) was defined as the angle of proximal rod contouring, which was represented by the angle between the cephalad endplate of the UIV and the caudal endplate of the second vertebra caudal to the UIV. Unmatched proximal rod contouring was regarded if the postoperative PRCA-PJA difference was greater than 5°. RESULTS: This study finally included 73 patients. The mean age at the index surgery was 6.5 ± 2.2 years (range, 2-10 years). Mean follow-up lasted 5.0 ± 1.7 years (range, 2-9 years). They received mean 4.6 ± 1.6 lengthening procedures. There were 13 patients who were observed with PJK (18%). In comparison with the non-PJK group, the PJK group showed a larger preoperative major curve (82 ± 21° vs 70 ± 17°, P = 0.041) and global kyphosis (57 ± 6° vs. 44 ± 15°, P = 0.044). In addition, the PJK group had significantly larger postoperative PJA (10 ± 3 vs. 5 ± 3, P<0.001) and greater postoperative PJA-PRCA (6 ± 3 vs. 3 ± 3, P = 0.031). The proportion of patients with unmatched proximal rod contouring in PJK group was significantly higher than that in the non-PJK group (69% vs. 25%). Multiple logistic regression showed that preoperative GK>50°, postoperative PJA>10 and postoperative unmatched proximal rod contouring were the risk factors in predicting PJK after TGR treatment. CONCLUSION: Approximately 18% EOS patients experienced PJK after TGR treatment. Unmatched proximal rod contouring may be an independent risk factor of PJK occurrence, in addition to greater preoperative GK and larger postoperative PJA.

Incidence, Management and Outcome of Delayed Deep Surgical Site Infection Following Spinal Deformity Surgery: 20-Year Experience at a Single Institution.

STUDY DESIGN: A retrospective study. OBJECTIVES: To investigate the incidence, management and outcome of delayed deep surgical site infection (SSI) after the spinal deformity surgery. METHODS: This study reviewed 5044 consecutive patients who underwent spinal deformity corrective surgery and had been followed over 2 years. Delayed deep SSI were defined as infection involving fascia and muscle and occurring >3 months after the initial procedure. An attempt to retain the implant were initially made for all patients. If the infection failed to be eradicated, the implant removal should be put off until solid fusion was confirmed, usually more than 2 years after the initial surgery. Radiographic data at latest follow-up were compared versus that before implant removal. RESULTS: With an average follow-up of 5.3 years, 56 (1.1%) patients were diagnosed as delayed deep SSI. Seven (12.5%) patients successfully retained instrumentation and there were no signs of recurrence during follow-up (average 3.4 years). The remaining patients, because of persistent or recurrent infection, underwent implant removal 2 years or beyond after the primary surgery, and solid fusion was detected in any case. However, at a minimum 1-year follow-up (average 3.9 years), an average loss of 9° in the thoracic curve and 8° in the thoracolumbar/lumbar curves was still observed. CONCLUSIONS: Delayed deep SSI was rare after spinal deformity surgery. To eradicate infection, complete removal of implant may be required in the majority of delayed SSI. Surgeons must be aware of high likelihood of deformity progression after implant removal, despite radiographic solid fusion.

Impact of lumbar fusion on sitting spinopelvic balance: Multisegmental versus monosegmental.

OBJECTIVES: To compare the differences in sagittal spinopelvic parameters between patients receiving monosegmental or multisegmental lumbar fusion and to assess the impact of fusion length on sitting balance. METHODS: The current study recruited 41 patients who had undergone lumbar fusion, consisting of 18 in the monosegmental group and 23 in the multisegmental group. And the control group included 50 lumbar degenerative patients who had no previous spinal fusion surgery. Spinopelvic parameters of patients were assessed: sagittal vertical axis, pelvic tilt, sacral slope, pelvic incidence, thoracic kyphosis, lumbar lordosis, and proximal femur angles. RESULTS: We observed significant differences in sitting TK (P = 0.031), LL (P = 0.012), PT (P = 0.009) and SVA (P = 0.009) among the three groups. When transitioning from standing to sitting, the multisegmental group had the least change in SVA (P = 0.016), PT (P = 0.043), and LL (P = 0.009), with a compensatory increase in TK (P = 0.021). Moderate to strong correlations were found between the change in the LL and those in the SVA (r = -0.548, P = 0.001), PT (r = -0.600, P = 0.001), and SS (r = 0.623, P = 0.001). CONCLUSION: Multisegmental lumbar fusion significantly limits the lumbar mobility and affects the ability to compensate postural changes. Reducing the fusion segments as much as possible is of particular value in preserving lumbar mobility and maintaining the compensatory mechanism of spinopelvis.

Contribution of postoperative vertebral remodeling to reversal of vertebral wedging and prevention of correction loss in patients with adolescent Scheuermann's kyphosis.

OBJECTIVE: This study aimed to investigate reversal of vertebral wedging and to evaluate the contribution of vertebral remodeling to correction maintenance in patients with adolescent Scheuermann's kyphosis (SK) after posterior-only instrumented correction. METHODS: A retrospective cohort study of patients with SK was performed. In total, 45 SK patients aged 10-20 years at surgery were included. All patients received at least 24 months of follow-up and had Risser sign greater than grade 4 at latest follow-up. Patients with Risser grade 3 or less at surgery were assigned to the low-Risser group, whereas those with Risser grade 4 or 5 were assigned to the high-Risser group. Radiographic data and patient-reported outcomes were collected preoperatively, immediately postoperatively, and at latest follow-up and compared between the two groups. RESULTS: Remarkable postoperative correction of global kyphosis was observed, with similar correction rates between the two groups (p = 0.380). However, correction loss was slightly but significantly less in the low-Risser group during follow-up (p < 0.001). The ratio between anterior vertebral body height (AVBH) and posterior vertebral body height (PVBH) of deformed vertebrae notably increased in SK patients from postoperation to latest follow-up (p < 0.05). Loss of correction of global kyphosis was significantly and negatively correlated with increased AVBH/PVBH ratio. Compared with the high-Risser group, the low-Risser group had significantly greater increase in AVBH/PVBH ratio during follow-up (p < 0.05). The two groups had similar preoperative and postoperative Scoliosis Research Society-22 questionnaire scores for all domains. CONCLUSIONS: Obvious reversal in wedge deformation of vertebrae was observed in adolescent SK patients. Patients with substantial growth potential had greater vertebral remodeling and less correction loss. Structural remodeling of vertebral bodies has a positive effect and protects against correction loss. These results could be help guide treatment decision-making.

Coronal imbalance after growing rod treatment in early-onset scoliosis: a minimum of 5 years' follow-up.

OBJECTIVE: The objective of this study was to investigate the incidence and risk factors of coronal imbalance (CI) in patients with early-onset scoliosis (EOS) who underwent growing rod (GR) treatment. METHODS: A consecutive series of 61 patients with EOS (25 boys and 36 girls, mean age 5.8 ± 1.7 years) who underwent GR treatment was retrospectively reviewed. Postoperative CI was defined as postoperative C7 translation on either side ≥ 20 mm. Patients were divided into an imbalanced and a balanced group. Coronal patterns were classified into three types: type A (C7 translation < 20 mm), type B (C7 translation ≥ 20 mm with C7 plumb line [C7PL] shifted to the concave side of the curve), and type C (C7 translation ≥ 20 mm and a C7PL shifted to the convex side of the curve). RESULTS: Each patient had an average of 5.3 ± 1.0 lengthening procedures and was followed for an average of 6.2 ± 1.3 years. Eleven patients (18%) were diagnosed with CI at the latest distraction, 5 of whom graduated from GRs and underwent definitive fusion. However, these patients continued to present with CI at the last follow-up evaluation. The proportion of preoperative type C pattern (54.5% vs 16.0%, p = 0.018), immediate postoperative apical vertebral translation (30.4 ± 13.5 mm vs 21.2 ± 11.7 mm, p = 0.025), lowest instrumented vertebra tilt (11.4° ± 8.2° vs 7.3° ± 3.3°, p = 0.008), and spanned obliquity angle (SOA) (9.7° ± 10.5° vs 4.1° ± 4.5°, p = 0.006) values in the imbalanced group were significantly higher than in the balanced group. Multiple logistic regression demonstrated that a preoperative type C pattern and immediate postoperative SOA > 11° were independent risk factors for postoperative CI. CONCLUSIONS: The incidence of CI in patients with EOS who underwent GR treatment was 18%. This complication could only be slightly improved after definitive spinal fusion because of the autofusion phenomenon. A preoperative type C pattern and immediate postoperative SOA > 11° were found to be the risk factors for CI occurrence at the latest follow-up.

Optimal Reconstruction of Sagittal Alignment According to Global Alignment And Proportion Score Can Reduce Adjacent Segment Degeneration After Lumbar Fusion.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study was to investigate the ability of Global Alignment and Proportion (GAP) score to predict the occurrence of adjacent segment degeneration (ASD) after fusion surgery for lumbar degenerative diseases. SUMMARY OF BACKGROUND DATA: The recently developed GAP score was applied to predict postoperative complications for adult spinal deformity, as well as to facilitate future outcome-based research on optimal treatment for various spinal conditions. However, it remains unclear whether reconstruction of alignment according to GAP score can reduce the ASD rates. METHODS: This study retrospectively reviewed 126 consecutive patients who had undergone lumbar fusion and had been followed over 2 years. Pre- and postoperative radiographs and MRI were analyzed for ASD. GAP scores were calculated based on the early postoperative spinopelvic parameters. Cochran-Armitage test of trend was performed to investigate the association between GAP score and the occurrence of ASD. Receiver-operating characteristic curves were used to analyze the predictive accuracy of the GAP score for ASD. RESULTS: Radiographical ASD (R-ASD) and symptomatic ASD (S-ASD) were diagnosed in 44 (34.9%) patients and in 13 (10.3%) patients, respectively. The patients with a proportioned spinopelvic state according to the GAP score had significantly lower rates of ASD (R-ASD and S-ASD) or S-ASD than those with a moderately or severely disproportioned spinopelvic state. The area under curve for the GAP score predicting ASD and S-ASD was 0.691 (95% confidence interval [CI]: 0.596∼0.785, P < 0.01) and 0.865 (95% CI: 0.771∼0.958, P < 0.01), respectively. CONCLUSION: Our study revealed a significant association between postoperative GAP score and occurrence of ASD after lumbar fusion surgery. Setting surgical goals according to the GAP score may help reduce the occurrence of ASD, especially for S-ASD.Level of Evidence: 4.

Point Set Registration With Similarity and Affine Transformations Based on Bidirectional KMPE Loss.

Robust point set registration is a challenging problem, especially in the cases of noise, outliers, and partial overlapping. Previous methods generally formulate their objective functions based on the mean-square error (MSE) loss and, hence, are only able to register point sets under predefined constraints (e.g., with Gaussian noise). This article proposes a novel objective function based on a bidirectional kernel mean p -power error (KMPE) loss, to jointly deal with the above nonideal situations. KMPE is a nonsecond-order similarity measure in kernel space and shows a strong robustness against various noise and outliers. Moreover, a bidirectional measure is applied to judge the registration, which can avoid the ill-posed problem when a lot of points converges to the same point. In particular, we develop two effective optimization methods to deal with the point set registrations with the similarity and the affine transformations, respectively. The experimental results demonstrate the effectiveness of our methods.

The Association between Metabolically Healthy Obesity, Cardiovascular Disease, and All-Cause Mortality Risk in Asia: A Systematic Review and Meta-Analysis.

We investigated the association among metabolically healthy obesity (MHO), cardiovascular disease (CVD)risk, and all-cause mortality in the Asian population. We searched databases from inception to 16 November, 2019 and pooled data using a random-effects model. Subgroup analysis was conducted according to the following comparison groups: MHNW (without overweight or underweight participants) and MHNO (non-obese, including overweight and underweight participants). Nineteen studies were included. The mean Newcastle-Ottawa Scale score was 7.8. Participants with MHO had a significantly higher CVD risk (odds ratio (OR) = 1.36, 95% confidence interval (CI) = 1.13-1.63) and significantly lower risk of all-cause mortality (OR = 0.88, 95% CI = 0.78-1.00) than the comparison group. Subgroup analyses revealed participants with MHO had a significantly higher CVD risk than MHNW participants (OR = 1.61; 95% CI = 1.24-2.08; I2 = 73%), but there was no significant difference compared with MHNO participants (OR, 1.04; 95% CI, 0.80-1.36; I2 = 68%). Participants with MHO had a significantly lower risk of all-cause mortality (OR = 0.83; 95% CI = 0.78-0.88; I2 = 9%) than MHNO participants, but a borderline significantly higher risk of all-cause mortality than MHNW participants (OR = 1.30; 95% CI = 0.99-1.72; I2 = 0%). The CVD risk and all-cause mortality of the MHO group changed depending on the control group. Thus, future studies should select control groups carefully.

Tyrosine kinase inhibitors for advanced or metastatic thyroid cancer: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Radioiodine-refractory advanced or metastatic thyroid cancer has poor prognosis. We conducted a meta-analysis of randomized controlled trials to evaluate the effectiveness and safety of tyrosine kinase inhibitors (TKIs) for advanced or metastatic thyroid cancer treatment. METHODS: Studies published up to April 2017 were selected. The pooled effect size was calculated through meta-analysis by using random effects models. Outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (RR), and adverse events (AEs). RESULTS: Six studies examining 1615 patients were included. TKI treatment significantly improved PFS in patients with differentiated thyroid cancer (DTC; hazard ratio [HR] = 0.43; 95% confidence interval [CI], 0.23-0.82) and those with medullary thyroid cancer (MTC; HR = 0.36; 95% CI, 0.22-0.58). TKI treatment significantly prolonged OS in patients with DTC (HR = 0.74; 95% CI, 0.58-0.95). The TKI treatment group exhibited a significantly improved partial response rate (risk ratio = 15.8; 95% CI, 1.77-140.69) but a significantly higher number of AEs compared with the control group. CONCLUSION: TKIs significantly improved PFS and RR in patients with advanced or metastatic DTC or MTC. We recommend thoroughly evaluating patients' health status and cautiously using TKIs to maximize their benefits and minimize their toxicity.