The Role of Pelvic Compensation in Sagittal Balance and Imbalance: The Impact of Pelvic Compensation on Spinal Alignment and Clinical Outcomes Following Adult Spinal Deformity Surgery.

BACKGROUND AND OBJECTIVES: The Scoliosis Research Society (SRS)-Schwab system does not include a pelvic compensation (PC) subtype, potentially contributing to gaps in clinical characteristics and treatment strategy for deformity correction. It also remains uncertain as to whether PC has differing roles in sagittal balance (SB) or imbalance (SI) status. To compare radiological parameters and SRS-22r domains between patients with failed pelvic compensation (FPC) and successful pelvic compensation (SPC) based on preoperative SB and SI. METHODS: A total of 145 adult spinal deformity patients who received deformity correction were analyzed. Radiographic and clinical outcomes were collected for statistical analysis. Patients were classified into 4 groups based on the median value of PT/PI ratio (PTr) and the cutoff value of SB. Patients with low PTr and high PTr were defined as FPC and SPC, respectively. Radiographic and clinical characteristics of different groups were compared. RESULTS: Patients with SPC exhibited significantly greater improvements in lumbar lordosis, pelvic tilt, PTr, and T1 pelvic angle as compared to patients with FPC, irrespective of SB or SI. No apparent differences in any of SRS-22r domains were observed at follow-up when comparing the SB-FPC and SB-SPC patients. However, patients with SI-SPC exhibited significantly better function, self-image, satisfaction, and subtotal domains at follow-up relative to those with SI-FPC. When SI-FPC and SI-SPC patients were subdivided further based on the degree of PI-LL by adjusting for age, the postoperative function and self-image domains were significantly better in the group with overcorrection of PI-LL than undercorrection of PI-LL in SI-FPC patients. However, no differences in these SRS-22r scores were observed when comparing the subgroups in SI-SPC patients. CONCLUSION: Flexible pelvic rotation is associated with benefits to the correction of sagittal parameters, irrespective of preoperative SB or SI status. However, PC is only significantly associated with clinical outcomes under SI. Patients with SI-FPC exhibit poorer postoperative clinical outcomes, which should be recommended to minimize PI-LL.

The impact of frailty on clinical outcomes of older patients undergoing enhanced recovery after lumbar fusion surgery: A prospective cohort study.

BACKGROUND: Frailty is recognized as a surrogate for physiological age and has been established as a valid and independent predictor of postoperative morbidity, mortality, and complications. ERAS can enhance surgical safety by minimizing stress responses in frail patients, enabling surgeons to discharge patients earlier. However, the question of whether and to what extent the frailty impacts the post-ERAS outcomes in older patients remains. MATERIALS AND METHODS: An evidence-based ERAS program was implemented in our center from January 2019. This is a prospective cohort study of patients aged ≥75 years who underwent open transforaminal lumbar interbody fusion (TLIF) for degenerative spine disease from April 2019 to October 2021. Frailty was assessed with the Fried frailty scale (FP scale), and patients were categorized as non/prefrail (FP 0-2) or frail (FP ≥ 3). The preoperative variables, operative data, postoperative outcomes and follow-up information were compared between the two groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for 90-day major complications and prolonged length of hospital stay (LOS) after surgery. RESULTS: A total of 245 patients (age of 79.8 ± 3.4 yr) who had a preoperative FP score recorded and underwent scheduled TLIF surgery were included in the final analysis. Comparisons between non-frail and prefrail/frail patients revealed no significant difference in age, sex, and surgery-related variables. Even after adjusting for multiple comparisons, the association between Fried frailty and ADL-dependency, IADL-dependency, and malnutrition remained significant. Preoperative frailty was associated with increased rates of postoperative adverse events. A higher CCI grade was an independent predictor for 90-day major complications, while Fried frailty and MNA-SF scores <12 were predictive of poor postoperative recovery. CONCLUSION: Frail older patients had more adverse post-ERAS outcomes after TLIF compared to non/prefrail older patients. Continued research and multidisciplinary collaboration will be essential to refine and optimize protocols for surgical care in frail older adults.

Radiographic and surgery-related predictive factors for increased segmental lumbar lordosis following lumbar fusion surgery in patients with degenerative lumbar spondylolisthesis.

OBJECTIVE: This study aimed to evaluate preoperative (pre-op) radiographic characteristics and specific surgical interventions in patients with degenerative lumbar spondylolisthesis (DLS) who underwent lumbar fusion surgery (LFS), with a focus on analyzing predictors of postoperative restoration of segmental lumbar lordosis (SLL). METHODS: A retrospective review at a single center identified consecutive single-level DLS patients who underwent LFS between 2016 and 2022. Radiographic measures included disc angle (DA), SLL, lumbar lordosis (LL), anterior/posterior disc height (ADH/PDH), spondylolisthesis percentage (SP), intervertebral disc degeneration, and paraspinal muscle quality. Surgery-related measures included cage position, screw insertion depth, spondylolisthesis reduction rate, and disc height restoration rate. A change in SLL ≥ 4° indicated increased segmental lumbar lordosis (ISLL), and unincreased segmental lumbar lordosis (UISLL) < 4°. Propensity score matching was employed for a 1:1 match between ISLL and UISLL patients based on age, gender, body mass index, smoking status, and osteoporosis condition. RESULTS: A total of 192 patients with an average follow-up of 20.9 months were enrolled. Compared to UISLL patients, ISLL patients had significantly lower pre-op DA (6.78° vs. 11.84°), SLL (10.73° vs. 18.24°), LL (42.59° vs. 45.75°), and ADH (10.09 mm vs. 12.21 mm) (all, P < 0.05). ISLL patients were predisposed to more severe intervertebral disc degeneration (P = 0.047) and higher SP (21.30% vs. 19.39%, P = 0.019). The cage was positioned more anteriorly in ISLL patients (67.00% vs. 60.08%, P = 0.000), with more extensive reduction of spondylolisthesis (- 73.70% vs. - 56.16%, P = 0.000) and higher restoration of ADH (33.34% vs. 8.11%, P = 0.000). Multivariate regression showed that lower pre-op SLL (OR 0.750, P = 0.000), more anterior cage position (OR 1.269, P = 0.000), and a greater spondylolisthesis reduction rate (OR 0.965, P = 0.000) significantly impacted SLL restoration. CONCLUSIONS: Pre-op SLL, cage position, and spondylolisthesis reduction rate were identified as significant predictors of SLL restoration after LFS for DLS. Surgeons are advised to meticulously select patients based on pre-op SLL and strive to position the cage more anteriorly while minimizing spondylolisthesis to maximize SLL restoration.

Structural characterization and immunomodulatory activity of a water-soluble polysaccharide from Poria cocos.

In order to investigate the structural characteristics and immunomodulatory effects of Poria cocos polysaccharides, a water-soluble homogeneous polysaccharide (PCP-2) was isolated by water extraction and alcohol precipitation and further purified by Cellulose DEAE-52 and Sephacryl S-100HR column chromatography. PCP-2 is a heteropolysaccharide composed of glucose, galactose, mannose, and fucose in a molar ratio of 42.0: 35.0: 13.9: 9.1. It exhibits a narrow molecular weight distribution at 2.35 kDa with a branching degree of 37.1 %. The main chain types of PCP-2 include 1,3-ß-D-Glc and 1,6-ß-D-Glc as the backbone glucans and 1,6-α-D-Gal as the backbone heterogalactan. In vitro experiments demonstrate that PCP-2 directly stimulate RAW264.7 cell proliferation and secretion of inflammatory factors such as NO and TNF-α. In cyclophosphamide (CTX)-induced mice, it promotes the development of thymus and spleen immune organs, elevates the blood levels of IgG, IgA, IgM and CD3+CD4+ T cells, increases the intestinal villus height/ crypt depth ratio and improves gut barrier dysfunctions. These findings suggest that PCP-2 is a natural fungal polysaccharide with broad spectrum of immunoenhancing effects, which can significantly ameliorate the immunocompromised state.

Fusion with and without lever reduction in degenerative lumbar spondylolisthesis: a retrospective study.

BACKGROUND: The reduction of slipped vertebra is often performed during surgery for degenerative lumbar spondylolisthesis (DLS). This approach, while potentially improving clinical and radiological outcomes, also carries a risk of increased complications due to the reduction process. To address this, we introduced an innovative lever reduction technique for DLS treatment. This study aims to investigate the clinical efficacy, radiological outcomes, and complications of fusion with or without lever reduction. METHODS: We conducted a retrospective review of prospectively collected data from a registry of patients who underwent lumbar fusion surgery for DLS, with a follow-up of at least 24 months. Self-reported measures included visual analog scale (VAS) for back or leg pain, Oswestry Disability Index (ODI), and the achievement of minimal clinically important difference (MCID). Radiological assessments encompassed spondylolisthesis percentage (SP), focal lordosis (FL), and lumbar lordosis (LL). Complications were categorized using the modified Clavien-Dindo classification (MCDC) scheme. Patients were assigned to the reduction group (RG) and non-reduction group (NRG) based on the application of the lever reduction technique. Clinical and radiological outcomes at baseline, immediately after surgery, and at the last follow-up were compared. RESULTS: A total of 281 patients were analyzed (123 NRG, 158 RG). Baseline patient demographics, comorbidities, and surgical characteristics were similarly distributed between groups except for operating time (NRG 129.25 min, RG 138.04 min, P = .009). Both groups exhibited significant clinical improvement after surgery (all, P = .000), with no substantial difference between groups (VAS, ODI, or the ability to reach MCID). Patients in RG showed statistically lower SP and higher FL during follow-up (all, P = .000). LL was comparable at different time points within each group or at the same time point between the two groups (all, P > .050). The overall complication rate (NRG 38.2%, RG 27.2%, P = .050) or specific complication rates per MCDC were similar between groups (all, P > .050). Patients in RG were predisposed to a lower risk of adjacent segment degeneration (ASDeg) (NRG 9.8%, RG 6.3%, P = .035). CONCLUSIONS: There were no significant differences in postoperative measures such as VAS scores for back and leg pain, ODI, the ability to reach MCID, overall complication rate, or specific complication rates per MCDC between surgical approaches. However, fusion with lever reduction demonstrated a notable advantage in restoring segmental spinal sagittal alignment and reducing the occurrence of ASDeg compared to in situ fusion.

Radiographic predictors of reaching minimal clinically important difference following lumbar fusion surgery in patients with degenerative lumbar spondylolisthesis.

PURPOSE: The present study aimed to (1) compare sagittal alignment between patients with degenerative lumbar spondylolisthesis (DLS) who reached or missed the minimal clinically important difference (MCID) for clinical outcomes following lumbar fusion surgery (LFS) and (2) identify radiographic predictors associated with MCID achievement in DLS patients. METHODS: A total of 91 single-level DLS patients who underwent LFS and had a minimum of 1-year follow-up were enrolled in this study. The assessed radiographic parameters included thoracic kyphosis, lumbar lordosis (LL), segmental lumbar lordosis (SLL), slip percentage, sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), and sagittal vertical axis. Changes in radiographic parameters were determined by subtracting the preoperative value from the final follow-up measurement. Clinical outcomes were assessed using the Oswestry Disability Index (ODI) and the visual analog scale (VAS) for both back and leg pain. MCID values were set at 10 points for ODI, 2.1 points for VAS back pain, and 2.8 points for VAS leg pain. Patients were assigned to the reached MCID (rMCID) and missed MCID (mMCID) groups based on the postoperative (post-op) recovery of clinical outcomes. RESULTS: At the last follow-up, 68.1% (62/91), 72.5% (66/91), and 76.9% (70/91) of patients reached MCID for ODI, VAS back pain, and VAS leg pain, respectively. Concerning ODI, the rMCID group exhibited higher post-op LL (47.93° vs. 42.95°, P = 0.044), higher post-op SLL (17.08° vs. 14.41°, P = 0.032), higher post-op SS (34.46° vs. 30.63°, P = 0.027), higher ∆LL (5.90° vs. 2.44°, P = 0.017), higher ∆SLL (4.63° vs. - 1.03°, P < 0.001), higher ∆SS (4.76° vs. 1.23°, P = 0.002), lower post-op PT/PI (36.95% vs. 42.01%, P = 0.049), lower ∆PT (- 3.71° vs. 1.05°, P < 0.001), lower ∆PT/PI (- 7.45% vs. 1.97%, P < 0.001), and lower ∆PI-LL (- 5.43° vs. - 3.71°, P = 0.011) than the mMCID group. Regarding VAS back pain, the rMCID group showed higher post-op SLL (17.06° vs. 14.05°, P = 0.021), higher post-op SS (34.34° vs. 30.33°, P = 0.027), higher ∆SLL (3.93° vs. - 0.09°, P < 0.001), and lower ∆PT (- 2.91° vs. - 0.30°, P = 0.039) than the mMCID group. For VAS leg pain, higher ∆SLL (3.55° vs. 0.41°, P = 0.003) was observed in the rMCID group than in the mMCID group. Multivariate logistic regression analysis revealed that higher ∆SLL, higher ∆SS, and higher post-op SS were independent predictors for the achievement of MCID in patients with DLS. CONCLUSION: DLS patients who reached MCID following LFS demonstrated improved post-op spinopelvic alignment. Higher ∆SLL, higher ∆SS, and higher post-op SS were the critical parameters associated with MCID achievement in patients with DLS.

Clinical effectiveness of reduction and fusion versus in situ fusion in the management of degenerative lumbar spondylolisthesis: a systematic review and meta-analysis.

PURPOSE: To compare the clinical effectiveness of reduction and fusion with in situ fusion in the management of patients with degenerative lumbar spondylolisthesis (DLS). METHODS: The systematic review was conducted following the PRISMA guidelines. Relevant studies were identified from PubMed, Embase, Scopus, Cochrane Library, ClinicalTrials.gov, and Google Scholar. The inclusion criteria were: (1) comparative studies of reduction and fusion versus in situ fusion for DLS patients, (2) outcomes reported as VAS/NRS, ODI, JOA score, operating time, blood loss, complication rate, fusion rate, or reoperation rate, (3) randomized controlled trials and observational studies published in English from the inception of the databases to January 2023. The exclusion criteria included: (1) reviews, case series, case reports, letters, and conference reports, (2) in vitro biomechanical studies and computational modeling studies, (3) no report on study outcomes. The risk of bias 2 (RoB2) tool and the Newcastle-Ottawa scale was conducted to assess the risk of bias of RCTs and observational studies, respectively. RESULTS: Five studies with a total of 704 patients were included (375 reduction and fusion, 329 in situ fusion). Operating time was significantly longer in the reduction and fusion group compared to in situ fusion group (weighted mean difference 7.20; 95% confidence interval 0.19, 14.21; P = 0.04). No additional significant intergroup differences were noted in terms of other outcomes analyzed. CONCLUSION: While the reduction and fusion group demonstrated a statistically longer operating time compared to the in situ fusion group, the clinical significance of this difference was minimal. The findings suggest no substantial superiority of lumbar fusion with reduction over without reduction for the management of DLS.

Compensation Characteristics of Spinal Sagittal Malalignment According to Pelvic Incidence in Elderly Patients with Degenerative Lumbar Spinal Stenosis.

OBJECTIVE: Compensation characteristics of spinal sagittal malalignment according to pelvic incidence (PI) have yet to be elucidated. This study aimed to investigate the difference in compensatory segments according to PI in elderly patients with degenerative lumbar spinal stenosis (DLSS). METHODS: This retrospective study included 196 patients (143 females, 53 males) suffering from DLSS with an average age of 66.73 years in our department. Sagittal parameters were obtained on the whole spinal lateral radiograph, including T1-T12 slope (T1S-T12S), Cobb angle (CA) of the functional units of the thoracic spine, thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), PI, the ratio of PT to PI (PT/PI), PI minus LL mismatch (PI-LL), sagittal vertical axis (SVA). Patients were divided into the low and high PI groups according to the median value of PI. With reference to the value of SVA and PI-LL, each PI group was further grouped into the balance subgroup (SVA < 50 mm, PI-LL ≤10°), hidden imbalance subgroup (SVA < 50 mm, PI-LL > 10°), and imbalance subgroup (SVA ≥50 mm). Independent samples t-test/Mann-Whitney U test, one-way ANOVA/Kruskal-Wallis test, and Person correlation analysis were utilized for statistical test. RESULTS: The median value of PI was 47.65°. 96 and 100 patients were assigned to low and high PI groups, respectively. Correlation analysis indicated that the T8-T12 slope and T10-T12 slope were associated with PI-LL in the high and low PI groups, respectively (all, p < 0.01). For segmental lordosis, T8-9 to T11-12 CA and T10-11 to T11-12 CA were associated with PI-LL in the high and low PI groups, respectively (all, p < 0.01). In the high PI cohort, T8-12 CA and PT increased significantly from the balance to imbalance subgroups (both, p < 0.05). In the low PI cohort, T10-12 CA and PT first increased and then decreased from the balance to imbalance subgroups (both, p < 0.05). CONCLUSION: T8-12 was the main compensatory segment of the thoracic spine in patients with high PI, while it was T10-12 in patients with low PI. In addition, the compensation potential of the lower thoracic spine and pelvis in patients with low PI was inferior to those with high PI.

Global Coronal Malalignment in Degenerative Lumbar Scoliosis and Priority-Matching Correction Technique to Prevent Postoperative Coronal Decompensation.

STUDY DESIGN: A prospective case-control study. OBJECTIVE: To analyze global coronal malalignment (GCM) in degenerative lumbar scoliosis (DLS) and to prospectively investigate the performance of priority-matching correction technique on preventing postoperative coronal imbalance. METHODS: A total of 444 DLS inpatients and outpatients were recruited. GCMs were classified into 2 types: Type 1, GCM with thoracolumbar (TL/L) curve as the main contribution on coronal imbalance; Type 2, GCM with lumbosacral (LS) curve as the main contribution on coronal imbalance. Patients receiving priority-matching correction were assigned to Group P-M and receiving traditional correction were assigned to Group T form August 2020. The fundamental principle of priority-matching technique was to first correct the key curve contributing to coronal imbalance rather than the curve with greater magnitude. RESULTS: Type 1 GCM accounted for 45% and Type 2 GCM accounted for 55% of patients. Type 2 GCM was detected to have greater LS Cobb angle and L4 tilt. At 1-year follow-up, 29.8% of patients with Type 2 GCM, whereas 11.7% of patients with Type 1 GCM were observed to have postoperative coronal decompensation. Patients with postoperative imbalance were revealed to have greater preoperative LS Cobb angle and L4 tilt and smaller correction extent of LS curve and L4 tilt. 6.25% of patients developed postoperative coronal imbalance in Group P-M, whereas 40.5% developed in Group T. CONCLUSION: Highlighting priority and aggressive correction of the key curve to coronal imbalance, priority-matching technique was proved to be able to limit the development of postoperative coronal decompensation.

The effect of sagittal alignment, coronal balance, and segmental stability on preoperative patient-reported outcomes in patients with degenerative lumbar spondylolisthesis.

OBJECTIVE: The aim of this study was to investigate the association between spinal alignment and preoperative patient-reported outcomes (PROs) in patients with degenerative lumbar spondylolisthesis (DLS) and to identify the independent risk factors for worse preoperative PROs. METHODS: In total, 101 patients suffering from DLS were retrospectively studied within a single medical center. Age, sex, height, weight, and body mass index were uniformly recorded. PRO-related indicators include the Oswestry Disability Index (ODI), the Japanese Orthopedic Association's (JOA) score, and the visual analog scale (VAS) for back and leg pain. Sagittal alignment, coronal balance, and stability of the L4/5 level were evaluated through whole-spine anteroposterior and lateral radiographs and dynamic lumbar X-ray. RESULTS: Increasing age (P = 0.005), higher sagittal vertical axis (SVA) (P < 0.001), and global coronal imbalance (GCI) (P = 0.023) were independent risk factors for higher ODI. Patients with GCI had lower JOA scores (P = 0.001) than those with balanced coronal alignment. Unstable spondylolisthesis (P < 0.001) and GCI (P = 0.009) were two vital predictors of VAS-back pain. Increasing age (P = 0.031), local coronal imbalance (LCI) (P < 0.001), and GCI (P < 0.001) were associated with higher VAS-leg pain. Moreover, patients with coronal imbalance also exhibited significant sagittal malalignment based on the subgroup analysis. CONCLUSION: DLS patients with higher SVA, unstable spondylolistheses, a combination of LCI/GCI, or increasing age were predisposed to have more severe subjective symptoms before surgery.

The effect of interlaminar Coflex stabilization in the topping-off procedure on local and global spinal sagittal alignment.

PURPOSE: To investigate the effect of interlaminar Coflex stabilization (ICS) at various segments in the topping-off procedure on local and global spinal sagittal alignment. METHODS: Eighty-nine consecutive patients with degenerative lumbar spinal stenosis (DLSS) who underwent ICS and transforaminal lumbar interbody fusion (TLIF) were retrospectively reviewed. They were divided into Group A (L4-L5 ICS + L5-S1 TLIF), Group B (L3-L4 ICS + L4-S1 TLIF), and Group C (L2-L3 ICS + L3-S1 TLIF) according to their fusion levels. The measured local sagittal parameters included the implanted segmental angle (ISA), intervertebral disc angle (IDA), intervertebral foreman height (IFH), and disc height. The assessed global sagittal parameters included thoracic kyphosis, lumbar lordosis (LL), the fused segment angle (FSA), the sacral slope, the pelvic tilt, pelvic incidence, and the sagittal vertical axis. The Oswestry Disability Index (ODI) and visual analog scales (VAS) were recorded to evaluate the clinical outcomes. RESULTS: Regarding the local alignment parameters, the ISA and IDA decreased immediately after surgery in Groups A and B, followed by an increase at the last follow-up (all, P < 0.05). Conversely, the IFH of Groups A and B first increased after surgery and then decreased to approximately the original value (all, P < 0.05). No significant differences were evident between the local sagittal parameters at different time points in Group C. Regarding the global sagittal profiles, the LL and FSA exhibited a significant postoperative increase (both at P < 0.05) in all the groups. All three groups displayed significant improvements in the ODI, VAS-back pain, and VAS-leg pain. Furthermore, 4.5% (4/89) of the patients exhibited radiographic adjacent segment degeneration (ASD) at the last follow-up. CONCLUSION: ICS during topping-off surgery led to a temporary loss of local lordosis, especially in the lower lumbar segment, while the intervertebral space realigned after middle-term follow-up. The topping-off procedure with ICS is a feasible and promising surgical option of DLSS since it reduces fusion levels and prevents ASD development.

The ratio of cervical lordosis to C7 slope represents the reciprocal change between cervical sagittal alignment and global spinal alignment.

PURPOSE: This retrospective cross-sectional study investigated variations in the ratio of cervical lordosis to C7 slope (CL/C7S) at different stages of global sagittal balance to better understand how global sagittal alignment affects cervical alignment. METHODS: A total of 255 patients with the degenerative lumbar disease were retrospectively studied within a single medical center. Whole spine radiographs were used to evaluate sagittal parameters, mainly including occiput-C2 lordosis (OC2), cervical lordosis (CL), C7 slope (C7S), the ratio of cervical lordosis to C7 slope (CL/C7S), cervical sagittal vertical axis (CSVA), thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), PI minus LL mismatch (PI-LL), and sagittal vertical axis (SVA). Patients were divided into the balance group (SVA < 50 mm, PI-LL ≤ 10°), hidden imbalance group (SVA < 50 mm, PI-LL > 10°), and imbalance group (SVA > 50 mm). RESULTS: Significant correlations were found between CL/C7S and OC2 (r = - 0.334), CSVA (r = - 0.504), PI-LL (r = 0.189), and SVA (r = 0.309). Multivariable linear regression analysis indicated that patients in the hidden imbalance group had lower CL/C7S than those in the balance group (B = - 0.234, P < 0.001), whereas the value of CL/C7S in patients with imbalanced sagittal alignment was higher than those with balanced alignment (B = 0.164, P = 0.011). The mean value of CL/C7S was 0.71, 0.51, and 0.97 in the balance, hidden imbalance, and imbalance groups, respectively. The global spine tended to tilt forward as the LL decreased, while TK, PT, PI-LL, and SVA increased (all, P < 0.001) from the balance stage to the imbalance stage. CONCLUSIONS: CL/C7S tended to be lower when the thoracic extension increased to maintain global sagittal balance at the hidden imbalance stage. Inversely, CL/C7S increased significantly when the global spine showed severe anterior malalignment.

Preoperative Zung depression scale predicts outcomes in older patients undergoing short-segment fusion surgery for degenerative lumbar spinal disease.

PURPOSE: To identify the relationship between depression measured by Zung depression rating scale (ZDRS) and postoperative outcomes (including the patients reported outcomes [PRO] and clinical outcomes) two years after short-segment fusion surgery for degenerative lumbar spinal disease in older patients (aged 75 years and older). METHODS: We enrolled patients who underwent short-segment fusion surgery for lumbar degenerative disease from May 2018 to June 2020. All patients were assessed for depression using the ZDRS. Patients were included in the depression group and not-depressed group based on their scores. Preoperative baseline data were collected on characteristics, comorbidities, laboratory data, pain levels (visual analogue scale [VAS]), functional status (Oswestry Disability Index [ODI]), and surgery-related variables. The primary outcomes were PRO measures, including VAS, ODI and satisfaction two years after lumbar fusion surgery. Other outcomes included postoperative complications, the length of stay, and reoperation. Univariate and multivariate analyses were performed to identify the risk factors for poor satisfaction. RESULTS: A total of 231 patients (201 in not-depressed and 30 in depressed group) were enrolled in this study. There were no significant differences between the two groups for baseline data. Depressed group had higher rates of choices for dissatisfaction (36.7% vs. 14.0%, p = 0.015), higher VAS scores of low back pain (2.8 ± 2.3 vs. 1.6 ± 1.7, p = 0.012), and worse functional status (31.5 ± 22.5 vs 21.8 ± 19.9, p = 0.015) than the not-depressed group. Depressed patients reported significantly higher rates of postoperative complications and readmissions. Multivariate regression analysis revealed that depression (p = 0.001) was independently associated with postoperative dissatisfaction. CONCLUSION: Preoperative depression was a risk factor for postoperative dissatisfaction, worse functional status, readmission, and complications in older patients undergoing lumbar fusion surgery. Preoperative screening using the Zung depression scale helps inform decision-making when considering fusion surgery for patients aged 75 and older.

Changes in T1 slope and cervical sagittal vertical axis correlate to improved neurological function recovery after cervical laminoplasty.

Purpose: To investigate the influence of changes in T1 slope (T1S) and cervical sagittal vertical axis (CSVA) on cervical laminoplasty outcomes. Methods: Eighty-one patients with cervical spondylotic myelopathy (CSM) treated with cervical laminoplasty were enrolled in this study. Demographic parameters included age and follow-up time. Imaging data included occiput-C2 lordosis (OC2), C2-C7 Cobb angle (CL), T1S, CSVA. Outcome assessment indicators included the Japanese Orthopedic Association (JOA) score, JOA recovery rate, and neck disability index (NDI). All patients were grouped based on preoperative T1S and variation in CL after surgery, respectively. Patients with decreased CL postoperatively were further grouped according to whether they were combined with T1S reduction. Results: There were no significant differences in the final JOA score, JOA recovery rate, or NDI between patients with different T1S. Patients with loss of CL postoperatively had lower JOA score and JOA recovery rate, but higher NDI than patients with sustained CL. Furthermore, patients with CL loss but compensate for it with reduction in T1S had lower CSVA, higher JOA score and JOA recovery rate than those with CL loss alone. Conclusions: Decreased T1S postoperatively prevents the tendency of the cervical spine to tilt forward by regulating CSVA and facilitates recovery of neurological function after cervical laminoplasty.

The discrepancy between preoperative cervical sagittal vertical axis and T1 slope predisposes inferior clinical outcomes in patients with cervical spondylotic myelopathy after cervical laminoplasty.

Objective: Cervical sagittal parameters have been widely used to predict clinical outcomes in patients with cervical spondylotic myelopathy (CSM). This study aims to coin a novel cervical sagittal parameter defined as the ratio of cervical sagittal vertical axis to T1 slope (CSVA/T1S) and to investigate the correlation between CSVA/T1S and postoperative HRQOL after laminoplasty. Methods: A total of 102 CSM patients treated with cervical laminoplasty from our database were retrospectively reviewed. All patients were followed up for >12 months. Radiological parameters were measured using lateral cervical radiographs, including occiput-C2 lordosis (OC2), cervical lordosis (CL), CSVA, and T1S. Clinical parameters included the Japanese Orthopedic Association (JOA) score, neck disability index (NDI), and JOA recovery rate. Patients were grouped by preoperative T1S, T1S-CL, and CSVA/T1S value, respectively. Clinical and radiological outcomes were compared between the groups. Results: Patients with high CSVA/T1S had greater OC2 and CSVA but lower CL than those in the low CSVA/T1S group pre-and postoperatively. With respect to HRQOL results, the final NDI was 12.46 ± 9.11% in the low CSVA/T1S group, which was significantly lower than that in the high CSVA/T1S group (17.68 ± 8.81%, P = 0.040). Moreover, only CSVA/T1S was detected to be significantly correlated with final NDI (r = 0.310, P = 0.027). No significant correlation was found between clinical results and other cervical sagittal parameters, including T1S, CSVA, and T1S-CL. Conclusions: Preoperative CSVA/T1S was correlated with postoperative NDI in patients with CSM after cervical laminoplasty. Patients with low preoperative CSVA/T1S achieved better neurological function improvement after cervical laminoplasty. Cervical laminoplasty could be an appropriate choice for patients with lower preoperative CSVA/T1S.

Caloric restriction ameliorates high-fat diet induced cognitive deficits through attenuating neuroinflammation via the TREM2-PI3K/AKT signaling pathway.

Prolonged high-fat diet (HFD) feeding impairs cognitive function in rodents. However, the mechanism of caloric restriction (CR) for remedying HFD-induced cognitive dysfunction remains elusive. In the present study, we investigated the effect of CR on HFD-induced cognitive dysfunction and its possible mechanism. BALB/c mice were fed with HFD for 16 weeks and subsequently subjected to CR for 12 weeks. After cognitive function was evaluated by behavioral tests such as Morris water maze and three-chamber paradigm tests, the mice were sacrificed. The prefrontal cortex and hippocampus were rapidly harvested and deposited at -80 °C. The neuroprotective mechanisms of CR on HFD-induced cognitive deficits were evaluated by histopathological and electron microscopy observations, western blotting and immunofluorescence. Compared with the normal control group, HFD mice exhibited obvious cognitive deficits, glucose tolerance impairment, neuronal degeneration and abnormalities of synaptic ultrastructure in the cortex and hippocampus. CR treatment improved cognitive dysfunction and histopathological changes as well as increased the cognition-related protein levels of PSD-95, synaptophysin and BDNF. Meanwhile, HFD increased the protein levels of pro-inflammatory factors including iNOS, COX-2 and IL-1ß but decreased the protein levels of anti-inflammatory factors such as CD206, TGF-ß, Ym-1 and Arg 1 in the prefrontal cortex and hippocampus, downregulated the protein levels of TREM2 and PI3K and decreased the phosphorylation level of AKT, which can be reversed by CR treatment. Therefore, our results indicated that CR ameliorated cognitive deficits of mice induced by a high-fat diet. The underlying mechanism is associated with the attenuation of the neuroinflammatory response mediated by the TREM2-PI3K/AKT signaling pathway.

Saponins from Panax japonicus alleviate HFD-induced impaired behaviors through inhibiting NLRP3 inflammasome to upregulate AMPA receptors.

Obesity is characterized by a condition of low-grade chronic inflammation that facilitates development of numerous comorbidities and dysregulation of brain homeostasis. It is reported that obesity can lead to behavioral alterations such as cognitive decline and depression-like behaviors both in humans and rodents. Saponins from panax japonicus (SPJ) have been reported to exhibit anti-inflammatory action in mouse model of diet-induced obesity. We evaluated the neuroprotection of SPJ on high fat diet (HFD) induced impaired behaviors such as memory deficit and depressive-like behaviors, and explored the underlying mechanisms. 6-week male Balb/c mice were divided into normal control group (NC, 17% total calories from fat), HFD group (60% total calories from fat), and HFD treated with SPJ groups (orally gavaged with dosages of 15 mg/kg and 45 mg/kg), respectively. After treatment for 16 weeks, behavioral tests were performed to evaluate the cognition and depression-like behaviors of the mice. The underling mechanisms of SPJ on HFD-induced impaired behaviors were investigated through histopathological observation, Western blot analysis and immunofluorescence. Our results showed that HFD-fed mice caused behavioral disorders, neuronal degeneration as well as elevated neuroinflammation, which was partly involved in NLRP3 inflammasome that finally resulted in decreased protein levels of AMPA receptors and down-regulated phosphorylated levels of CaMKII and CREB in cortex and hippocampus. All the above changes in cortex and hippocampus induced by HFD were mitigated by SPJ treatment. SPJ treatment alleviated HFD-induced recognitive impairment and depression-like behaviors of mice, which could be partly due to the capacity of SPJ to mitigate neuroinflammation through inhibition of NLRP3 inflammasome and upregulation of AMPA receptors signaling pathway.

Panax notoginseng Saponins Attenuate Neuroinflammation through TXNIP-Mediated NLRP3 Inflammasome Activation in Aging Rats.

INTRODUCTION: Microglia-mediated inflammatory responses play a crucial role in aging-related neurodegenerative diseases. The TXNIP/NLRP3 pathway is a key pathway leading to microglial activation. Panax notoginseng Saponins (PNS) have been widely used for the treatment of stroke in China. OBJECTIVE: This study evaluates the anti-neuroinflammatory effect of PNS and investigates the mechanism via TXNIP-mediated NLRP3 inflammasome activation in aging rats. MATERIAL AND METHODS: Eighteen-month-old Sprague-Dawley rats were randomly divided into the aging control group and PNS treated groups (n=15 each group). For PNS-treated groups, rats were administrated food with PNS at the doses of 10 mg/kg and 30 mg/kg for consecutive 6 months until they were 24-month old. Rats from the aging control group were given the same food without PNS. Twomonth- old rats were purchased and given the same food until they were 6-months old as the adult control group (n = 15). Then, the cortex and hippocampus were rapidly harvested and deposited. H&E staining was used to assess histo-morphological changes. Western blotting was carried out to detect the protein expression. Immunofluorescence was employed to measure the co-localization of NLRP3, TXNIP and Iba-1. In vitro model was established by LPS+ATP co-incubation in the BV2 microglia cell line. RESULTS: Aging rats exhibited increased activation of microglia, accompanied by a high level of IL-1ß expression. Meanwhile, aging rats showed enhanced protein expression of TXNIP and NLRP3 related molecules, which co-localized with microglia. PNS treatment effectively reduced the number of degenerated neurons and reversed the activation of the TXNIP/NLRP3 inflammatory pathway. In vitro results showed that PNS up to 100 µg/ml had no significant toxicity on BV2 microglia. PNS (25, 50 µg/ml) effectively reduced the inflammatory response induced by LPS and ATP co-stimulation, thus inhibiting the expression of TXNIP/NLRP3 pathway-related proteins. DISCUSSION AND CONCLUSION: PNS treatment improved aging-related neuronal damage through inhibiting TXNIP mediated NLRP3 inflammasome activation, which provided a potential target for the treatment of inflammation-related neurodegenerative diseases.

[Improved effects of saponins from Panax japonicus on decline of cognitive function in natural aging rats via NLRP3 inflammasome pathway].

The aim of this paper was to investigate the effect of total saponins from Panax japonicus( SPJ) on cognitive decline of natural aging rats and its mechanism. Thirty male SD rats of eighteen month old were randomly divided into three groups: aged group,10 mg·kg~(-1) SPJ-treated group and 30 mg·kg~(-1) SPJ-treated group. The SPJ-treated groups were given SPJ at the dosages of 10 mg·kg~(-1) and 30 mg·kg~(-1),respectively,from the age of 18 to 24 months. Aged group were lavaged the same amount of saline,10 six-month-old rats were used as control group,with 10 rats in each group. The open field test,novel object recognition and Morris water maze were performed to detect the changes of cognitive function in each group. The changes of synaptic transmission of long-term potentiation( LTP) in hippocampal CA1 region were detected by field potential recording. Western blot was used to detect the protein levels of NLRP3,ASC,caspase-1 and the changes of Glu A1,Glu A2,CAMKⅡ,CREB and phosphorylation of CAMKⅡ,CREB in each group.The results showed that SPJ could improve the decline of cognitive function in aging rats,reduce the damage of LTP in the hippocampal CA1 region of aged rats,and decrease the expression of NLRP3,ASC,caspase-1 in aging rats. At the same time,SPJ could enhance the membrane expression of AMPA receptor( Glu A1 and Glu A2),and increase the expression of p-CAMKⅡand p-CREB in aging rats.SPJ could improve cognitive decline of natural aging rats,and its mechanism may be related to regulating NLRP3 inflammasome,thus regulating the membrane expression of AMPA receptor,and enhancing the expression phosphorylation of CAMKⅡ and CREB.