Modified pedicle subtraction osteotomy for osteoporotic vertebral compression fractures: a retrospective study of 104 patients.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCF) caused by osteoporosis is a common clinical fracture type. There are many surgical treatment options for OVCF, but there is a lack of comparison among different options. Therefore, we counted a total of 104 cases of OVCF operations with different surgical plans, followed up the patients, and compared the surgical outcome indications before, after and during the follow-up. METHOD: 104 patients who underwent posterior osteotomy (Modified PSO, SPO, PSO, VCR) and kyphosis correction surgery at our hospital between April 2006 and August 2021 with a minimum follow-up period of 24 months were included. All cases were injuries induced by a fall incurred while standing or lifting heavy objects without high-energy trauma. The mean CT value was 71 HU, which was below 110 HU, indicating severe osteoporosis. The indications for surgery included gait disturbance due to severe pain with pseudarthrosis, increased kyphotic angle, and progressive neurological symptoms. Pre- and postoperative CL, TLK, TK, PrTK, TKmax, GK, LL, PI, SS, PT, SVA, TPA, were investigated radiologically. Additionally, We evaluated estimated blood loss, surgical time and perioperative symptom. RESULT: The results show, after operation, TLK (37.32 ± 10.61° vs. 11.01 ± 8.06°, P < 0.001), TK (35.42 ± 17.64° vs. 25.62 ± 12.24°, P < 0.001), TKmax (49.71 ± 16.32° vs. 24.12 ± 13.34°, P < 0.001), SVA (44.91 ± 48.67 vs. 23.52 ± 30.21, P = 0.013), CL (20.23 ± 13.21° vs. 11.45 ± 9.85°, P = 0.024) and TPA (27.44 ± 12.76° vs. 13.91 ± 9.24°, P = 0.009) were improved significantly in modified Pedicle subtraction osteotomy (mPSO) after operation. During follow-up, TLK (37.32 ± 10.61° vs. 13.88 ± 10.02°, P < 0.001) and TKmax (49.71 ± 16.32° vs. 24.12 ± 13.34°, P < 0.001) were improved significantly in Modified PSO group. In additon, estimated blood loss (790.0 ± 552.2 ml vs. 987.0 ± 638.5 ml, P = 0.038), time of operation (244.1 ± 63.0 min vs. 292.4 ± 87.6 min, P = 0.025) were favorable in Modified PSO group compared to control group. CONCLUSION: To conclude, mPSO could acquire a favorable degree of kyphosis correction as well as fewer follow-up complications. Compared with other surgical methods, it also has the advantages of less surgical trauma and shorter operation time. It can be an effective solution for the treatment of OVCF.

Preoperative and follow-up variations of psoas major muscle are related to S1 screw loosening in patients with degenerative lumbar spinal stenosis.

BACKGROUND: It was reported the paraspinal muscle played an important role in spinal stability. The preoperative paraspinal muscle was related to S1 screw loosening. But the relationship between preoperative and postoperative change of psoas major muscle (PS) and S1 pedicle screw loosening in degenerative lumbar spinal stenosis (DLSS) patients has not been reported. This study investigated the effects of preoperative and follow-up variations in the psoas major muscle (PS) on the first sacral vertebra (S1) screw loosening in patients with DLSS. METHODS: 212 patients with DLSS who underwent lumbar surgery were included. The patients were divided into the S1 screw loosening group and the S1 screw non-loosening group. Muscle parameters were measured preoperatively and at last follow-up magnetic resonance imaging. A logistic regression analysis was performed to investigate the risk factors for S1 screw loosening. RESULTS: The S1 screw loosening rate was 36.32% (77/212). The relative total cross-sectional areas and relative functional cross-sectional areas (rfCSAs) of the PS at L2-S1 were significantly higher after surgery. The increased rfCSA values of the PS at L3-S1 in the S1 screw non-loosening group were significantly higher than those in the S1 screw loosening group. The regression analysis showed male, lower CT value of L1 and longer segment fusion were independent risk factors for S1 screw loosening, and postoperative hypertrophy of the PS was a protective factor for S1 screw loosening. CONCLUSIONS: Compared to the preoperative muscle, the PS size increased and fatty infiltration decreased after surgery from L2-3 to L5-S1 in patients with DLSS after short-segment lumbar fusion surgery. Postoperative hypertrophy of the PS might be considered as a protective factor for S1 screw loosening. MRI morphometric parameters and postoperative selected exercise of PS for DLSS patients after posterior lumbar fusion surgery might contribute to improvement of surgical outcome.

Deep Learning Model Coupling Wearable Bioelectric and Mechanical Sensors for Refined Muscle Strength Assessment.

Muscle strength (MS) is related to our neural and muscle systems, essential for clinical diagnosis and rehabilitation evaluation. Although emerging wearable technology seems promising for MS assessment, problems still exist, including inaccuracy, spatiotemporal differences, and analyzing methods. In this study, we propose a wearable device consisting of myoelectric and strain sensors, synchronously acquiring surface electromyography and mechanical signals at the same spot during muscle activities, and then employ a deep learning model based on temporal convolutional network (TCN) + Transformer (Tcnformer), achieving accurate grading and prediction of MS. Moreover, by combining with deep clustering, named Tcnformer deep cluster (TDC), we further obtain a 25-level classification for MS assessment, refining the conventional 5 levels. Quantification and validation showcase a patient's postoperative recovery from level 3.2 to level 3.6 in the first few days after surgery. We anticipate that this system will importantly advance precise MS assessment, potentially improving relevant clinical diagnosis and rehabilitation outcomes.

Impact of pelvic anteversion on spinopelvic alignment in an asymptomatic population: a dynamic perspective of standing and sitting.

BACKGROUND CONTEXT: A subgroup of patients with pelvic anteversion can present with an unusually large degree of lumbar lordosis (LL), a highly sloped sacrum, and a relatively small pelvic incidence (PI). Prior to lumbar surgery, it can be important to consider such unique sagittal alignment. However, until now, there has been a lack of a predictive model considering different pelvic alignments. Furthermore, the dynamic characteristics of an anteverted pelvis (AP) subgroup have also been unclear. PURPOSE: To build linear predictive formulas for LL that take pelvic anteversion into consideration and to explore the dynamic characteristics of an AP subgroup. STUDY DESIGN: Monocentric, cross-sectional study. PATIENT SAMPLE: Five hundred and sixty-five asymptomatic Chinese men and women between the ages of 18 and 80 years. OUTCOME MEASURES: Sagittal parameters including LL, lumbar lordosis minus thoracic kyphosis (LL-TK), PI, pelvic tilt (PT), pelvic incidence minus lumbar lordosis (PI-LL), sacral slope (SS), sacral slope divided by pelvic incidence (SS/PI), sagittal vertical axis (SVA), thoracic kyphosis (TK), and T1 (first thoracic vertebra) pelvic angle (TPA) were measured on whole spine radiographs obtained with participants in standing and sitting positions. METHODS: All participants underwent radiography in the standing position; 235 of them underwent additional radiography in the sitting position to allow measurement of sagittal parameters. The participants with pelvic anteversion were placed in an AP (anteverted pelvis) group. Sagittal parameters were compared between the AP group and the non-AP group, and predictive formulas for LL based on PI were created in both groups. In addition, changes in sagittal parameters from standing to sitting were compared in the AP group and a PI-matched control group. RESULTS: Of the 565 participants, 171 (30.3%) had pelvic anteversion. In comparison with the non-AP group, the AP group presented with larger LL, a larger SS, and a smaller PT, with relatively small PI. The predictive formulas for LL were LL=0.60° × PI+21.60° (R2=0.268; p<.001) in the whole cohort, LL=0. 83×PI+18.75° (R2=0.427; p<.001) in AP group, and LL=0.79°×PI+9.66° (R2=0.451; p<.001) in the non-AP group. In moving from standing to sitting, the AP group presented with a larger decrease in SS and LL compared with the control group, indicating different patterns of spinopelvic motion. CONCLUSIONS: In the cohort examined, 30.3% present with pelvic anteversion. Those with AP present with unique characteristics of spinopelvic alignment. In moving from standing to sitting, they exhibit different patterns of spinopelvic motion. We found that identifying the degree of anteversion in each person improves the accuracy of linear models for predicting the degree of LL, which in turn can make plans for spine surgery more accurate.

Involvement of DJ-1 in the pathogenesis of intervertebral disc degeneration via hexokinase 2-mediated mitophagy.

Intervertebral disc degeneration (IDD) is an important pathological basis for degenerative spinal diseases and is involved in mitophagy dysfunction. However, the molecular mechanisms underlying mitophagy regulation in IDD remain unclear. This study aimed to clarify the role of DJ-1 in regulating mitophagy during IDD pathogenesis. Here, we showed that the mitochondrial localization of DJ-1 in nucleus pulposus cells (NPCs) first increased and then decreased in response to oxidative stress. Subsequently, loss- and gain-of-function experiments revealed that overexpression of DJ-1 in NPCs inhibited oxidative stress-induced mitochondrial dysfunction and mitochondria-dependent apoptosis, whereas knockdown of DJ-1 had the opposite effect. Mechanistically, mitochondrial translocation of DJ-1 promoted the recruitment of hexokinase 2 (HK2) to damaged mitochondria by activating Akt and subsequently Parkin-dependent mitophagy to inhibit oxidative stress-induced apoptosis in NPCs. However, silencing Parkin, reducing mitochondrial recruitment of HK2, or inhibiting Akt activation suppressed DJ-1-mediated mitophagy. Furthermore, overexpression of DJ-1 ameliorated IDD in rats through HK2-mediated mitophagy. Taken together, these findings indicate that DJ-1 promotes HK2-mediated mitophagy under oxidative stress conditions to inhibit mitochondria-dependent apoptosis in NPCs and could be a therapeutic target for IDD.

Distal Junctional Failures in Degenerative Thoracolumbar Hyperkyphosis.

OBJECTIVE: Degenerative thoracolumbar hyperkyphosis (DTH) is a disease that negatively affects individual health and requires surgical intervention, yet the ideal surgical approach and complications, especially distal junctional failures (DJF), remain poorly understood. This study aims to investigate DJF in DTH and to identify the risk factors for DJF so that we can improve surgical decision-making, and advance our knowledge in the field of spinal surgery to enhance patient outcomes. METHODS: This study retrospectively reviewed 78 cases (late osteoporotic vertebral compression fracture [OVCF], 51; Scheuermann's kyphosis [SK], 17; and degenerative disc diseases [DDD], 10) who underwent corrective surgery in our institute from 2008 to 2019. Clinical outcomes were assessed using health-related quality of life (HRQOL) measures, including the visual analogue scale (VAS) scores for back and leg pain, the Oswestry disability index (ODI), and the Japanese Orthopaedic Association (JOA) scoring system. Multiple radiographic parameters, such as global kyphosis (GK) and thoracolumbar kyphosis (TLK), were assessed to determine radiographic outcomes. Multivariate logistic regression analysis was employed to identify the risk factors associated with DJF. RESULTS: HRQOL improved, and GK, TLK decreased at the final follow-up, with a correction rate of 67.7% and 68.5%, respectively. DJF was found in 13 of 78 cases (16.7%), two cases had wedging in the disc (L3-4) below the instrumentation, one case had a fracture of the lowest instrumented vertebrae (LIV), one case had osteoporotic fracture below the fixation, nine cases had pull-out or loosening of the screws at the LIV and three cases (23.1%) required revision surgery. The DJF group had older age, lower computed tomography Hounsfield unit (CT HU), longer follow-up, more blood loss, greater preoperative sagittal vertical axis (SVA), and poorer postoperative JOA and VAS scores (back). The change in TLK level was larger in the non-DJF group. Post-sagittal stable vertebrae (SSV) moved cranially compared with pre-SSV. CONCLUSION: Age, CT HU, length of follow-up, estimated blood loss, and preoperative SVA were independent risk factors for DJF. We recommend fixation of the two vertebrae below the apex vertebrae for DTH to minimize surgical trauma.

Relationship between the postoperative variations of paraspinal muscles and adjacent-segment degeneration in patients with degenerative lumbar spinal stenosis after posterior instrumented lumbar fusion.

OBJECTIVE: This study aimed to quantify pre- and postoperative paraspinal muscular variation following posterior lumbar interbody fusion (PLIF) in patients with degenerative lumbar spinal stenosis (DLSS) and measure the association of this variation with adjacent-segment degeneration (ASD). METHODS: Data from 149 patients who underwent L4-S1 PLIF for DLSS were collected. Patients were divided into radiologically confirmed ASD and control groups according to follow-up radiological findings. MRI was performed before surgery and at the last follow-up. Muscular parameters including the relative cross-sectional area (rCSA), relative functional cross-sectional area (rFCSA), relative total cross-sectional area (rTCSA), and fatty infiltration (FI) of the multifidus (MF), erector spinae (ES), and psoas major (PM) muscles were measured on preoperative and follow-up L2-S1 MR images. Logistic regression was used to investigate risk factors for ASD. RESULTS: The rate of radiological ASD was 42.3% at the final follow-up (mean 25.71 ± 8.35 months). At surgical levels, the rFCSA and rTCSA of the MF and ES muscles decreased. The FI of the MF from L2-3 to L5-S1 and ES muscles at L5-S1 significantly increased after surgery, while the rFCSA and rTCSA of the PM muscle increased and its FI decreased. At adjacent levels, the rFCSA and rTCSA of the MF muscle and rTCSA of the ES muscle decreased and the FI of the MF muscle increased postoperatively (p < 0.05), but the rFCSA and rTCSA of the PM muscle increased and its FI decreased (p < 0.05). The FIs of the MF, ES, and PM muscles at adjacent levels significantly differed between the ASD and control groups. Logistic regression analysis indicated that higher BMI (p = 0.002) and FI of the PM muscle at adjacent levels (p = 0.025) were significant risk factors for ASD. CONCLUSIONS: The functional area decreased in the MF and ES muscles and increased in the PM muscle after L4-S1 PLIF. A compensatory postoperative decrease in FI of the PM muscle at the adjacent level was a protective factor for ASD in DLSS patients after PLIF.

Risk Factors of Postoperative Coronal Balance Transition in Degenerative Lumbar Scoliosis.

STUDY DESIGN: Retrospective radiographic study. OBJECTIVE: To determine the potential risk factors influencing the transition of postoperative coronal balance in degenerative lumbar scoliosis (DLS) patients. SUMMARY OF BACKGROUND DATA: As time passes after surgery, the spinal sequence of DLS patients may dynamically shift from coronal balance to imbalance, causing clinical symptoms. However, the transition of postoperative coronal balance and its risk factors have not been effectively investigated. MATERIALS AND METHODS: We included 156 DLS patients. The cohort was divided into immediate postoperative coronal balance with follow-up balance (N=73) and follow-up imbalance (N=21), immediate postoperative coronal imbalance (CIB) with follow-up balance (N=23), and follow-up imbalance (N=39). Parameters included age, sex, classification of coronal balance, coronal balance distance, fusion of L5 or S1, location of apical vertebra, apical vertebral translation (AVT), Cobb angle of the main curve and lumbar-sacral curve, tilt and direction of L4/5, tilt and direction of upper instrumented vertebra (UIV), and Cobb angle of T1-UIV. Statistical testing was performed using chi-square/Fisher exact test, t tests or nonparametric tests, correlation testing, and stepwise logistic regression. RESULTS: We identified a significant difference in preoperative AVT, preoperative Cobb angle, and immediate postoperative UIV tilt between patients with and without follow-up balance. Logistic regression analysis demonstrated factors associated with follow-up CIB included preoperative AVT ( P =0.015), preoperative Cobb angle ( P =0.002), and tilt of immediate postoperative UIV ( P =0.018). Factors associated with immediate postoperative CIB in patients with follow-up coronal balance were sex, correction ratio of the main curve, and direction of L4. Logistic regression analysis further identified a correction ratio of main curve ≤0.7 ( P =0.009) as an important predictive factor. CONCLUSION: Patients with immediate postoperative coronal balance and higher preoperative AVT, preoperative Cobb angle, and tilt of immediate postoperative UIV were more likely to experience follow-up CIB. A correction ratio of the main curve ≤0.7 was an independent predictor of follow-up CIB. LEVEL OF EVIDENCE: 3.

Upper instrumented vertebrae selection criteria for degenerative lumbar scoliosis based on the hounsfield unit asymmetry of the first coronal reverse vertebrae: an observational study.

BACKGROUND: Selection of the upper instrumented vertebra (UIV) is crucial for surgical treatment of degenerative lumbar scoliosis (DLS), given the relevance of UIV in postoperative proximal adjacent segment degeneration (pASD). Our previous research found that selection of UIV not lower than (≤) the first coronal reverse vertebra (FCRV), which marks the turning point of Hounsfield unit (HU) asymmetry, could significantly reduce pASD. However, the degree of HU asymmetry can vary among patients, suggesting a demand for more individualized UIV selection criteria, which we aimed to develop using quantitative HU measurement in the current study. METHODS: We included 153 consecutive patients with DLS. Quantitative measurement of HU of both sides of the vertebrae of these patients was performed on three planes of CT reconstruction for average values and determination of FCRV. Pre- and postoperative X-ray plain films were examined for radiological measurements and determination of pASD. Further, 35 patients with lumbar disc herniation and without significant scoliosis were also included as the reference group, and their bilateral HU was measured. RESULTS: In all 153 patients, those with UIV ≤ FCRV had a significantly lower rate of pASD (9.4% vs. 24.6%, P = 0.011). The difference between HU of the left and right sides of the FCRV (dF) could range from close to 0-59.4. The difference between HU of the left and right sides of the vertebrae in the reference group had an average value of 5.21. In 101 dF ≥ 5 DLS patients, those with UIV ≤ FCRV had a significantly lower rate of pASD (7.6% vs. 28.6%, P = 0.005), while this rate was insignificant in the other 52 dF < 5 patients (13.3% vs. 18.2%, P = 0.708). No other general, radiological, or operative parameter was found to have significant influence on the occurrence of pASD. CONCLUSIONS: Selection of UIV ≤ FCRV can significantly reduce the risk of pASD for patients with DLS with dF ≥ 5. Trial Registration Not applicable, since this is an observational study.

Role of the Paraspinal Muscles in the Sagittal Imbalance Cascade: The Effects of Their Endurance and of Their Morphology on Sagittal Spinopelvic Alignment.

BACKGROUND: The role of paraspinal muscle degeneration in the cascade of sagittal imbalance is still unclear. This study aimed to compare paraspinal muscle degeneration in the 4 stages of sagittal imbalance: sagittal balance (SB), compensated sagittal balance (CSB), decompensated sagittal imbalance (DSI), and sagittal imbalance with failure of pelvic compensation (SI-FPC). In addition, it aimed to compare the effects paraspinal muscle endurance and morphology on sagittal spinopelvic alignment in patients with lumbar spinal stenosis. METHODS: A cross-sectional study of 219 patients hospitalized with lumbar spinal stenosis was performed. The isometric paraspinal extensor endurance test and evaluation of atrophy and fat infiltration of the paraspinal extensor muscles and psoas major on magnetic resonance imaging were performed at baseline. Spinopelvic parameters including lumbar lordosis, pelvic tilt, sacral slope, pelvic incidence, and the sagittal vertical axis were measured. RESULTS: The patients with lumbar spinal stenosis were divided into 67 with SB, 85 with CSB, 49 with DSI, and 17 with SI-FPC. There were significant differences in paraspinal muscle endurance and morphology among the 4 groups. Furthermore, the SI-FPC group had poorer paraspinal muscle endurance than either the SB or the CSB group. In multiple linear regression analysis, paraspinal muscle endurance and the relative functional cross-sectional area of the paraspinal extensor muscles were the independent predictors of the sagittal vertical axis, and the relative functional cross-sectional area of the psoas major was the independent predictor of relative pelvic version. CONCLUSIONS: This study indicated that paraspinal muscle degeneration is not only an initiating factor in pelvic retroversion but also a risk factor for progression from a compensated to a decompensated stage. Specifically, the impairment of muscle endurance in the CSB stage may be the reason why patients experience failure of pelvic compensation. In addition, paraspinal muscle endurance and muscle morphology (relative functional cross-sectional area of the paraspinal extensor muscles and psoas major) had different clinical consequences. LEVEL OF EVIDENCE: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

The Role of Thoracic Tilt in Identifying Thoracic Compensation and Predicting Proximal Junctional Kyphosis in Degenerative Lumbar Scoliosis.

STUDY DESIGN: A retrospective cohort study of consecutive patients. OBJECTIVE: To investigate the clinical value of thoracic tilt (TT) in characterizing thoracic compensation and predicting proximal junctional kyphosis (PJK) in degenerative lumbar scoliosis (DLS). SUMMARY OF BACKGROUND DATA: Thoracic compensation has been shown to be associated with the development of PJK, while thoracic shape and morphology in patients with DLS remain understudied. METHODS: Patients with DLS who underwent long-segment fusion were divided into a PJK group and a non-PJK group. Asymptomatic elderly volunteers were recruited as healthy controls. Thoracic parameters were measured in both cohorts, including the TT, T1-L1 pelvic angle (TLPA), T12 slope, thoracic kyphosis (TK, T4-T12), global thoracic kyphosis (GTK, T1-T12), and thoracolumbar kyphosis (TLK, T10-L2). Multivariate logistic regression was used to assess the association between TT and the development of PJK, adjusting for confounders. Multivariate linear regression was used to establish the predictive formula for TT. RESULTS: A total of 126 patients with DLS were enrolled, of which 37 (29.4%) developed PJK. Compared with 110 healthy controls, DLS patients had significantly greater TT, TLPA, T12 slope, and TLK as well as smaller TK and GTK (all P <0.001). Preoperatively, the PJK group showed significantly greater TT ( P =0.013), TLPA ( P <0.001), and TLK ( P =0.034) than the non-PJK group. No significant differences were found in TK and GTK before surgery. Postoperatively, the PJK group showed significantly greater TT ( P <0.001), TLPA ( P <0.001), TLK ( P <0.001), and proximal junctional angle ( P <0.001). Multivariate logistic regression analysis showed that greater postoperative TT was associated with the development of PJK. Multivariate linear regression analysis suggested that the regression formula was postoperative TT=0.675×T12slope+0.412×TK+0.158×TLK-4.808 ( R2 =0.643, P <0.001). CONCLUSIONS: The novel sagittal parameter TT can be used for the evaluation of thoracic compensation. Greater preoperative TT might represent a decompensated state of TK. Rebalancing the TT in a sagittal neutral position might help to prevent PJK in patients with DLS.

Open Surgical Treatments of Osteoporotic Vertebral Compression Fractures.

With an aging population, the osteoporotic vertebral compression fracture (OVCF) has become a constant concern for its physical and neurological complications, such as spinal kyphosis and refractory pains. Compared with traditional conservative treatments, the open surgery is more superior in some ways because of its direct decompression and correction. Various operation methods applying to different indications have been developed to deal with different fracture situations, including anterior, posterior, and combined surgery. In this review, we have concluded the latest developments of the surgery treating OVCF and the internal fixation as references for spinal surgeons of the choice of suitable treatments.

DJ-1-mediated p62 degradation delays intervertebral disc degeneration by inhibiting apoptosis of nucleus pulposus cells.

Intervertebral disc degeneration (IDD) is the most important pathological basis of degenerative spinal diseases, for which effective interventions are still lacking. Oxidative stress is considered to be one of the leading pathological mechanisms contributing to IDD. However, the exact role of DJ-1 as an essential member of the antioxidant defense system in IDD is still unclear. Therefore, the aim of this study was to investigate the role played by DJ-1 in IDD and to reveal its potential molecular mechanisms. Western blot and immunohistochemical staining assays were performed to detect the expression of DJ-1 in degenerative nucleus pulposus cells (NPCs). After overexpression of DJ-1 in NPCs by lentiviral transfection, DCFH-DA and MitoSOX fluorescent probes were used to evaluate the levels of reactive oxygen species (ROS); while western blot, TUNEL staining, and Caspase-3 activity were used to assess apoptosis. Immunofluorescence staining was used to demonstrate the relationship between DJ-1 and p62. After inhibition of lysosomal degradation function with chloroquine, p62 degradation and apoptosis in DJ-1 overexpressing NPCs were further examined. In vivo, we assessed the therapeutic effect of upregulated DJ-1 on IDD by X-ray, MRI and Safranin O-Fast green staining. The protein expression of DJ-1 was significantly decreased in degenerated NPCs, accompanied by increased apoptosis. However, overexpression of DJ-1 significantly inhibited the elevated ROS levels and apoptosis in NPCs under oxidative stress. Mechanistically, our results showed that upregulation of DJ-1 promoted p62 degradation via the autophagic lysosomal pathway and that the protective effect of DJ-1 on NPCs under oxidative stress was partially mediated by promoting lysosomal pathway degradation of p62. Moreover, intradiscal injection of adeno-associated virus for overexpression of DJ-1 mitigated the progression of IDD in rats. This study reveals that DJ-1 maintains the homeostasis of NPCs by promoting the degradation of p62 through the autophagic lysosomal pathway, suggesting that DJ-1 is a promising new target for IDD intervention.

Skullcapflavone II, a novel NQO1 inhibitor, alleviates aristolochic acid I-induced liver and kidney injury in mice.

Aristolochic acid I (AAI) is a well established nephrotoxin and human carcinogen. Cytosolic NAD(P)H quinone oxidoreductase 1 (NQO1) plays an important role in the nitro reduction of aristolochic acids, leading to production of aristoloactam and AA-DNA adduct. Application of a potent NQO1 inhibitor dicoumarol is limited by its life-threatening side effect as an anticoagulant and the subsequent hemorrhagic complications. As traditional medicines containing AAI remain available in the market, novel NQO1 inhibitors are urgently needed to attenuate the toxicity of AAI exposure. In this study, we employed comprehensive 2D NQO1 biochromatography to screen candidate compounds that could bind with NQO1 protein. Four compounds, i.e., skullcapflavone II (SFII), oroxylin A, wogonin and tectochrysin were screened out from Scutellaria baicalensis. Among them, SFII was the most promising NQO1 inhibitor with a binding affinity (KD = 4.198 µmol/L) and inhibitory activity (IC50 = 2.87 µmol/L). In human normal liver cell line (L02) and human renal proximal tubular epithelial cell line (HK-2), SFII significantly alleviated AAI-induced DNA damage and apoptosis. In adult mice, oral administration of SFII dose-dependently ameliorated AAI-induced renal fibrosis and dysfunction. In infant mice, oral administration of SFII suppressed AAI-induced hepatocellular carcinoma initiation. Moreover, administration of SFII did not affect the coagulation function in short term in adult mice. In conclusion, SFII has been identified as a novel NQO1 inhibitor that might impede the risk of AAI to kidney and liver without obvious side effect.

Which Global Sagittal Parameter Could Most Effectively Predict the Surgical Outcome for Patients With Adult Degenerative Scoliosis?

STUDY DESIGN: Retrospective study. OBJECTIVE: To evaluate the predictive effect of the 3 global sagittal parameters (Sagittal Vertical Axis [SVA], T1 Pelvic Angle [TPA], and relative TPA [rTPA]) in the surgical outcome of patients with adult degenerative scoliosis (ADS), then to define the optimum corrective goal based on the best of them. METHODS: 117 ADS patients were included in this study and followed-up for an average of 3 years. Functional evaluation and radiographs were assessed preoperatively and postoperatively. The predictive accuracy of SVA, TPA, and relative TPA was analyzed through receiver operating characteristic (ROC) curve. The cutoff value of TPA was obtained at the maximal Youden index from ROC curve. RESULTS: TPA most highly correlated with postoperative oswestry disability index (ODI). The best cutoff value of TPA was set at 19.3° (area under curve =0.701). TPA >19.3° was the highest risk factor in multivariate logistic regression analysis (OR = 7.124, P = 0.022). Patients with TPA <19.3° at 3 months after operation showed a better ODI than those with TPA >19.3°. Correcting TPA less than 19.3° for patients with preoperative TPA >19.3° attributed to a better health related quality of life (HRQOL) and sagittal balance at last follow-up. The formula "Postoperative TPA = 0.923 × PI - 0.241 × postoperative LL - 0.593 × postoperative SS - 2.471 (r = 0.914, r2 = 0.836, P < .001)" described the relation between SS, LL, PI, and TPA. CONCLUSION: TPA was a useful global parameter for the prediction of postoperative HRQOL for patients with ADS. Keeping TPA <19.3° could improve the postoperative HRQOL for ADS patients with preoperative TPA >19.3°, and TPA <19.3° could be an optimum correction target for patients with ADS.

Evaluation of Adjacent Segment With Pre-Existing Degeneration Using the Cerebrospinal Fluid Occlusion Sign on MRI Before Posterior Lumbar Fusion: A Multi-Center Observational Cohort Study.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: To evaluate whether pre-existing adjacent spinal canal stenosis (SCS) is associated with short-term outcomes after lumbar fusion surgery. METHODS: We included patients with lumbar spinal stenosis treated surgically between July 2015 and December 2017 at 4 centers. All patients had the same pathology, with L4-S1 as the culprit sections. Patients were divided into 2 groups based on the cerebrospinal fluid occlusion sign on MRI at the adjacent L3/4 level. Patients without SCS (grade 0) and with mild SCS (grade 1) were classified into the non-stenosis (NS) and mild stenosis (MS) groups, respectively. All patients underwent PLIF and completed at least 1-year follow-up. The incidence of adjacent segment degeneration (ASDeg) and clinical outcomes were compared between the 2 groups. RESULTS: A total of 308 patients (NS, 156; MS, 152) met the inclusion criteria. The incidence of ASDeg in the NS group (n = 40, 25.6%) was significantly lower than that in the MS group (n = 74, 48.7%; P < .001). The most frequent type of ASDeg in the 2 groups was the SCS-aggravated type. No significant difference was observed in adjacent segment disease incidence between the 2 groups (P = .243). The NS group had better outcomes according to the clinical function scores (P < .05). CONCLUSIONS: The cerebrospinal fluid occlusion sign on MRI is valuable for evaluating the adjacent segment with pre-existing degeneration. Patients with mild SCS in adjacent segments were more likely to have ASDeg, and the most frequent type of ASDeg was the SCS-aggravated type at early follow-up.

Paraspinal Muscle Degeneration as an Independent Risk for Loss of Local Alignment in Degenerative Lumbar Scoliosis Patients After Corrective Surgery.

STUDY DESIGN: Retrospective study. OBJECTIVES: To investigate the effect of paraspinal muscle degeneration on the maintenance of local and global alignment among degenerative lumbar scoliosis (DLS) patients after corrective surgery. METHODS: 98 DLS patients with a mean follow-up period of 38.3 months after corrective surgery were included. The T1 pelvic angle (TPA), lumbar lordosis (LL), pelvic incidence were measured preoperatively, immediate postoperatively and at last follow-up. All patients were divided into LL maintenance group (n = 21) and LL loss group (n = 77). For patients with well-aligned correction (immediate postoperative TPA ≤ 20°, n = 73), they were divided into TPA maintenance group (last follow-up TPA ≤ 20°) and TPA loss group (last follow-up TPA > 20°). The relative gross cross-sectional area (rGCSA) and fat infiltration (FI) of multifidus (MF) and erector spinae (ES), and the relative functional CSA (rFCSA) of psoas major (PS) were measured at L3, L4 and L5 on preoperative magnetic resonance imaging. RESULTS: MF rGCSA were significantly smaller in LL loss group than in LL maintenance group. Both MF rGCSA and PS rFCSA were significantly smaller and MF FI was significantly higher in TPA loss group than in TPA maintenance group. Binary logistic regression revealed that the MF rGCSA was an independent factor of LL loss; Large immediate postoperative TPA was an independent risk factor of TPA loss, but not the parameters of paraspinal muscles. CONCLUSION: The effect of paraspinal muscles in lower lumbar segments might be mainly focused on the maintenance of local alignment rather than the global alignment.

Impact of lumbar fusion on spinopelvic sagittal alignment from standing to sitting position: which factor is associated with postoperative functional limitations due to lumbar stiffness?

PURPOSE: To investigate the impact of lumbar fusion on spinopelvic sagittal alignment from standing to sitting position and the influencing factors of postoperative functional limitations due to lumbar stiffness. METHODS: A total of 107 patients who undertook posterior lumbar interbody fusion were included. Patients were divided into two groups: Group A (lumbosacral fusion; n = 43) and Group B (floating fusion; n = 64). Spinopelvic parameters in standing and sitting position including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), fusion segment lordosis (FSL), upper residual lordosis (URL), lower residual lordosis (LRL), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), sagittal vertical axis (SVA) and T1 pelvic angle (TPA) were measured before and after lumbar fusion. The Lumbar Stiffness Disability Index (LSDI) was used to assess functional limitations due to lumbar stiffness. RESULTS: Accompanied by increased postoperative LSDI, the values of changes from standing to sitting (∆) were reduced in some parameters compared with the preoperative values. ∆PT and ∆SS significantly decreased in both two groups. In Group A, ∆LL significantly decreased with increased ∆URL. In Group B, ∆LL, ∆URL and ∆LRL showed no significant difference before and after surgery. Multiple linear regression analysis showed that age and ∆PT independently influenced the postoperative LSDI in Group A. CONCLUSION: After lumbar fusion, changes of lumbopelvic sagittal parameters from standing to sitting would be restricted. Adjacent segment lordosis could partially compensate for this restriction. For patients with lumbosacral fusion, postoperative functional limitations due to lumbar stiffness were related to age and the postoperative ∆PT from standing to sitting.

5-ALA mediated photodynamic therapy with combined treatment improves anti-tumor efficacy of immunotherapy through boosting immunogenic cell death.

Photodynamic therapy (PDT) is clinically promising in destructing primary tumors and immunotherapy awakes host immunity to control distant metastases. 5-aminolevulinic acid (5-ALA), a smart photosensitizer, converts into a physiological PDT agent with no dark toxicity in vivo. In this study, we found for the first time 5-ALA-PDT induced colorectal cancer (CRC) cells death by immunogenic cell death (ICD) upon AKT inhibition. Dying cancer cells induced by 5-ALA-PDT efficiently activated bone-marrow derived dendritic cells (BMDCs). Simultaneously, autophagy was observed after AKT inhibition by 5-ALA-PDT. Besides, we found cells died more remarkable by ICD under a circumstance of low occurrence of autophagy. To evaluate the effects of 5-ALA-PDT in vivo, we applied subcutaneous tumor mouse model and delightedly found 5-ALA-PDT induced a systemic antitumor immune response to control both primary tumors and distant metastases. Meanwhile, 5-ALA-PDT enhanced Th1 immunity, leading cytotoxic T lymphocyte response, and raised tumor-specific T cells. Combining with Chloroquine (CQ), 5-ALA-PDT further augmented tumor-specific immunity effects indicating protective role of autophagy. Together, the combination therapy of 5-ALA-PDT and autophagy inhibitor synergistically led to a novel clinical approach and potential ICD-based tumor vaccine for CRC patients.

Clinical Application of the Roussouly Classification in the Sagittal Balance Reconstruction of 101 Adolescent Idiopathic Scoliosis Patients.

PURPOSE: Although Roussouly classification has been widely used in spinal surgery, it was mainly applied to degenerative scoliosis patients and correlational studies concerning adolescent idiopathic scoliosis (AIS) are still insufficient. This retrospective study explored the clinical application of Roussouly classification in surgeries and prognosis prediction for AIS. METHODS: This clinical research selected 101 AIS patients who received surgeries between August 2005 and November 2019. Whole spine standing radiographs were obtained for each patient preoperatively, postoperatively, and at the last follow-up (>24 months). All patients were classified into "theoretical types" and "current types." Patients were further divided into mismatch or match groups based on the consistency of their current type and theoretical type. The main parameters include: proximal junctional angle (PJA), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), fixed thoracic kyphosis (TK), global TK, fixed lumbar lordosis (LL), global LL, thoracic tilt, proximal thoracic alignment (PTA), lumbar tilt, spino-sacral angle (SSA), and spinal tilt (ST). RESULTS: A total of 47.5% of AIS patients were subject to a preoperative mismatch of Roussouly classification. There was a significant difference in PI-LL between the preoperative mismatch and match groups (p = 0.008). There was a significant difference in the rate of PI-LL deformity between the match and mismatch groups with a preoperative mismatch (p = 0.037). A significant difference in thoracic tilt was observed between the postoperative mismatch and match groups (p = 0.019). The preoperative mismatch group has a higher risk of postoperative PI-LL malformation than match group (OR = 2.303, 95% CI: 1.026, 5.165). When mismatch occurred postoperatively, there were significant differences between groups in the rate of pelvic deformity (p = 0.002) and PI-LL deformity (p = 0.025) at the last follow-up. Compared with the postoperative match group, mismatch group had an increased risk of pelvic deformity (OR = 5.029, 95% CI: 1.618, 15.629) and PJK deformity (OR = 3.017, 95% CI: 1.709, 11.375) at the last follow-up. Short Form-36 and Scoliosis Research Society 22 score of the match group was significantly higher than that of the mismatch group at the last follow-up. CONCLUSION: The Roussouly classification mismatch before or after operation leads to increased risks of PI-LL deformity and pelvis deformity postoperatively or at the follow-up, which seriously worsens the clinical symptoms and prognosis of patients. Therefore, recovering to the theoretical type in Roussouly classification may effectively improve patients' prognosis.