Co-culturing nucleus pulposus mesenchymal stem cells with notochordal cell-rich nucleus pulposus explants attenuates tumor necrosis factor-α-induced senescence.

BACKGROUND: Cell therapy for the treatment of intervertebral disc degeneration (IDD) faces serious barriers since tissue-specific adult cells such as nucleus pulposus cells (NPCs) have limited proliferative ability and poor regenerative potential; in addition, it is difficult for exogenous adult stem cells to survive the harsh environment of the degenerated intervertebral disc. Endogenous repair by nucleus pulposus mesenchymal stem cells (NPMSCs) has recently shown promising regenerative potential for the treatment of IDD. Notochordal cells (NCs) and NC-conditioned medium (NCCM) have been proven to possess regenerative ability for the treatment of IDD, but this approach is limited by the isolation and passaging of NCs. Our previous study demonstrated that modified notochordal cell-rich nucleus pulposus (NC-rich NP) has potential for the repair of IDD. However, whether this can protect NPMSCs during IDD has not been evaluated. METHODS: In the current study, tumor necrosis factor (TNF)-α was used to mimic the inflammatory environment of IDD. Human NPMSCs were cocultured with NC-rich NP explants from healthy rabbit lumbar spine with or without TNF-α. Cell proliferation and senescence were analyzed to investigate the effect of NC-rich NP explants on TNF-α-treated NPMSCs. The expression of mRNA encoding proteins related to matrix macromolecules (such as aggrecan, Sox-9, collagen Iα, and collagen IIα), markers related to the nucleus pulposus cell phenotype (including CA12, FOXF1, PAX1, and HIF-1α), and senescence markers (such as p16, p21, and p53), senescence-associated proinflammatory cytokines (IL-6), and extracellular proteases (MMP-13, ADAMTS-5) was assessed. The protein expression of CA12 and collagen II was also evaluated. RESULTS: After a 7-day treatment, the NC-rich NP explant was found to enhance cell proliferation, decrease cellular senescence, promote glycosaminoglycan (GAG), collagen II, and CA12 production, upregulate the expression of extracellular matrix (ECM)-related genes (collagen I, collagen II, SOX9, and ACAN), and enhance the expression of nucleus pulposus cell (NPC) markers (HIF-1α, FOXF1, PAX1, and CA12). CONCLUSION: Modified NC-rich NP explants can attenuate TNF-α-induced degeneration and senescence of NPMSCs in vitro. Our findings provide new insights into the therapeutic potential of NC-rich NP for the treatment of IDD.

The Effectiveness and Safety of Selective Lumbar Decompression in Diagnostic Doubt Patients: A Retrospective Control Study.

BACKGROUND: Our previous study demonstrated that selective nerve root block (SNRB) can influence decision-making in lumbar surgery by guiding the selection of nerve roots targeted for decompression in diagnostic doubt patients (DDPs). However, further studies were needed to determine whether this selective decompression (SD) procedure would result in similar clinical outcomes and reduce the perioperative parameters and postoperative complications as compared to the non-selective decompression (NSD) procedure. OBJECTIVE: The specific goal of this study is to compare clinical outcomes, perioperative parameters, and complications between SD and NSD procedures in DDPs. STUDY DESIGN: A retrospective control study. SETTING: Gaozhou People's Hospital. METHODS: From January 2009 to January 2011, 57 lumbar surgery patients with diagnostic doubt were retrospectively reviewed. Basic patient parameters, as well as perioperative and postoperative data were compared between the selective and non-selective decompression groups. Clinical outcomes were evaluated using the visual analog scale (VAS), Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) scores, and JOA recovery rates. RESULTS: Both groups showed significant improvement in VAS, ODI, and JOA scores between preoperative and postoperative measurements. The differences in VAS and ODI scores between groups were not significant at 3 and 60 months postoperatively (both P > 0.05). In addition, there was no significant difference in JOA recovery rate (P = 0.659) and survival rate (P = 0.586) during the 60 months following surgery. However, distinctly superior perioperative parameters (operation time and hospital stay, blood loss and drainage volume, laminectomy numbers, and fusion segment numbers) were observed in the SD group (P < 0.001 for each score). Moreover, the SD-treated group experienced significantly fewer adverse events postoperatively (P = 0.036). LIMITATIONS: The limitations of this study lie in the size of the study and selection of patients and in the fact that it was not feasible to include all cases of diagnostic doubt. CONCLUSIONS: On the basis of the 5-year follow-up data, we suggest that the SD procedure guided by SNRB is an effective and safe method for the surgical treatment of DDPs. This procedure produces superior perioperative parameters when compared with the conventional NSD procedure, but has a comparable clinical outcome. Moreover, the benefits of SD surgery include fewer perioperative and postoperative complications.

Minimally invasive procedure reduces adjacent segment degeneration and disease: New benefit-based global meta-analysis.

OBJECTIVE: Adjacent segment pathology (ASP) is a common complication presenting in patients with axial pain and dysfunction, requiring treatment or follow-up surgery. However, whether minimally invasive surgery (MIS), including MIS transforaminal / posterior lumbar interbody fusion (MIS-TLIF/PLIF) decreases the incidence rate of ASP remains unknown. The aim of this meta-analysis was to compare the incidence rate of ASP in patients undergoing MIS versus open procedures. METHODS: This systematic review was undertaken by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. We searched electronic databases, including PubMed, EMBASE, SinoMed, and the Cochrane Library, without language restrictions, to identify clinical trials comparing MIS to open procedures. The results retrieved were last updated on June 15, 2016. RESULTS: Overall, 9 trials comprising 770 patients were included in the study; the quality of the studies included 4 moderate and 5 low-quality studies. The pooled data analysis demonstrated low heterogeneity between the trials and a significantly lower ASP incidence rate in patients who underwent MIS procedure, compared with those who underwent open procedure (p = 0.0001). Single-level lumbar interbody fusion was performed in 6 trials of 408 patients and we found a lower ASP incidence rate in MIS group, compared with those who underwent open surgery (p = 0.002). Moreover, the pooled data analysis showed a significant reduction in the incidence rate of adjacent segment disease (ASDis) (p = 0.0003) and adjacent segment degeneration (ASDeg) (p = 0.0002) for both procedures, favoring MIS procedure. Subgroup analyses showed no difference in follow-up durations between the procedures (p = 0.93). CONCLUSION: Therefore, we conclude that MIS-TLIF/PLIF can reduce the incidence rate of ASDis and ASDeg, compared with open surgery. Although the subgroup analysis did not indicate a difference in follow-up duration between the two procedures, larger-scale, well-designed clinical trials with extensive follow-up are needed to confirm and update the findings of this analysis.

[Analysis of clinical outcomes of simplified treatment of lumbar spondylolisthesis with adjacent segment degeneration by MAST Quadrant].

OBJECTIVE: To explore the method and clinical effect of MAST Quadrant for lumbar spondylolisthesis with adjacent segment degeneration. METHODS: From April 2014 to January 2016, 36 cases of lumbar spondylolisthesis with adjacent segment degeneration were treated by MAST Quadrant(target nerve decompression and transforaminal lumbar interbody fusion or articulationes zygapophysiales fusion by unilateral fixation with MAST Quadrant). Twenty-three cases were degenerative lumbar spondylolisthesis and 13 cases were isthmic lumbar spondylolisthesis. According to Meyerding grade of spondylolisthesis, 16 cases were grade I, 17 cases were grade II, and 3 cases were grade III. Visual analogue score (VAS), Oswesty Disability Index (ODI) and JOA score were used to evaluate the clinical outcome. RESULTS: The amount of intraoperative bleeding was 230 to 480 ml with an average of 340 ml and the amount of postoperative blood loss was 15 to 80 ml with an average of 43 ml. Operative time was 176 to 240 min with an average of 193 min; X-ray exposure time was 2 to 6 s with an average of 3.6 s. Two cases were complicated with dural tear without nerve injury during operation. Thirty cases were followed up from 12 to 17 months with an average of 15.2 months. VAS scores for preoperative, 5 days, 3 months after surgery were 7.6±1.7, 1.9±0.4, 0.8±0.4 respectively, and there was significant difference before and after operation(P<0.05). The ODI scores for preoperative and 3 months after surgery were 35.9±1.2 and 3.7±0.7 respectively, and there was significant difference before and after operation(P<0.05). JOA scores for preoperative, 5 days, 1 months, 3 months after surgery were 13.2±0.4, 24.4±0.4, 27.4±0.1, 27.9±0.5 respectively, and there was significant difference before and after operation(P<0.05). CONCLUSIONS: MAST Quadrant can be applied to treat lumbar spondylolisthesis with adjacent segment degeneration, and the minimally invasive sugical technique is a safe and effective method, with the advantage of simple operation, fast recovery.

Intrathecal morphine verse femoral nerve block for pain control in total knee arthroplasty: A meta-analysis from randomized control trials.

OBJECTIVE: Total knee arthroplasty (TKA) is usually associated with postoperative pain. The objective of this systematic review and meta-analysis was to evaluate the effectiveness and safety of femoral nerve block compared with intrathecal morphine for pain management after TKA. METHODS: Potentially relevant literature was identified from electronic databases including Medline, PubMed, Embase, ScienceDirect and the Cochrane Library. Gray academic studies were also identified from the reference of included literature. There was no language restriction. Pooling of data was carried out using Stata 11.0. RESULTS: Four randomized controlled trials (RCTs) involving 185 patients met the inclusion criteria. The meta-analysis indicated that there were no significant differences in terms of Visual Analog Scale (VAS) score at 6 h (standard mean difference (SMD) = -0.09, 95% CI: -1.62 to 1.43, P = 0.903), 12 h (weighted mean difference (WMD) = 1.84, 95% CI: -8.01 to 11.69, P = 0.714) or 24 h (WMD = 1.56, 95% CI: -14.31 to 17.42, P = 0.8474). No significant difference were found regarding morphine consumption at 6 h (WMD = -0.84, 95% CI: -2.52 to 0.85, P = 0.332), 12 h (WMD = 0.031, 95% CI: -3.304 to 0.3366, P = 0.985), 24 h (WMD = 0.21, 95% CI: -7.32 to 7.75, P = 0.956) or incidence of postoperative vomit and nausea (risk difference (RD) = -0.01, 95% CI: -0.15 to 0.12, P = 0.847). There was a significant difference between the groups in terms of the risk of itching postoperatively (RD = 0.41, 95% CI: 0.29 to 0.54, P < 0.001). CONCLUSIONS: Femoral nerve block provides equal postoperative pain control compared with intrathecal morphine following total knee arthroplasty, although there were fewer side effects in the FNB groups. In contrast, FNB was performed with an additional procedure and required a special apparatus. Both methods are effective at pain control following TKA.

Full-Endoscopic Procedures Versus Traditional Discectomy Surgery for Discectomy: A Systematic Review and Meta-analysis of Current Global Clinical Trials.

BACKGROUND: Traditional discectomy surgery (TDS) provides good or excellent results in clinical surgical discectomy but may induce neural adhesion, spinal structural damage, instability, and other complications. The potential advantages of full-endoscopic (FE) procedures over standard TDS include less blood loss, less postoperative pain, shorter hospitalization, and an earlier return to work. However, more evidence is needed to support this new technology in clinical applications. OBJECTIVE: The aim of this systematic review and meta-analysis was to compare the safety and efficacy of FE and TDS. STUDY DESIGN: Comprehensive systematic review and meta-analysis of the literature. METHODS: Electronic databases, including PubMed, EMBASE, SinoMed, and Cochrane Library, were searched to identify clinical therapeutic trials comparing FE to TDS for discectomy. RESULTS: Six trials comprising 730 patients were included, and the overall quality of the literature was moderate, including 4 Grade I levels of evidence (4 randomized controlled trials, [RCTs]) and 2 Grade II levels (2 non-RCTs). The pooled data revealed no difference in reoperation rates between FE and TDS (P = 0.94), but the complication rate was significantly lower in the FE group (3.86%) than in the TDS group (11.4%). Perioperative parameters (operation time, blood loss, hospitalization time, and return to work days) were significantly lower in the FE group (P < 0.05 for all groups using either score). Postoperative pain and neurology score assessments were conducted at 4 different time points at 3 months, 6 months, 12 months, and 24 months. Significant differences were detected in the following: lumbar North American Spine Society (NASS) pain at 6 months (P = 0.008); cervical NASS neurology at 6 months (P = 0.03); visual analog scale (VAS) score in leg at 3 months (P < 0.001); VAS score in arm at 24 months (P = 0.002); VAS score in neck at 3 months, 6 months, and 12 months after therapy (P = 0.003, P = 0.004, P = 0.01); and VAS score in neck at 3 months and 6 months (P = 0.01, P = 0.004). Moreover, the pooled data revealed no statistically significant differences in improvements in the Oswestry disability index (ODI), instability (X-ray), and Hilibrand criteria (P > 0.05 for all groups). LIMITATIONS: Only 6 studies were included, 4 of which had the same authors. Between-study heterogeneity due to differences in socioeconomic factors, nutrition, and matching criteria is difficult to avoid. CONCLUSIONS: Based on this meta-analysis of 24 months of clinical results, we conclude that the FE procedure is as effective as TDS but has the additional benefits of lower complication rates and superior perioperative parameters. In addition, patients may experience less pain with FE techniques due to a smaller incision and less operative injury. However, large-volume, well-designed RCTs with extensive follow-up are needed to confirm and update the findings of this analysis.

Efficacy and safety of bone marrow-derived cell transplantation for spinal cord injury: a systematic review and meta-analysis of clinical trials.

PURPOSE: Bone marrow-derived cells (BMDCs) for clinical transplantation were carried out many years in treating spinal cord injury (SCI) without a clear conclusion. This study aimed to evaluate the safety and efficacy of BMDC transplantation in treatment of SCI patients. METHOD: Electronic databases, including PubMed, EMBASE, MEDLINE, and the Cochrane library, were searched to identify clinical therapeutic trials studying the application of BMDC transplantation in SCI. RESULTS: Overall the quality of the 24 studies was low, including one Grade I level of evidence, six Grade II levels, three Grade III levels, and 14 Grade IV levels. With a maximum of six-yr follow-up, the procedure-related complications were minor and temporary, without serious adverse events (p = 0, n = 594). AIS improvement rate was analyzed in favor of BMDCs 6.13 (95% CI, 3.0-12.51; p < 0.001). In patient with complete (AIS A) and chronic SCI, the application of cell transplantation numbers between n × (10(7) -10(8) ) seemed to be more beneficial (p < 0.05 for all groups). CONCLUSIONS: Based on short-medium terms following up, BMDC transplantation appears to be safe and valid in SCI patients, more effective in chronic and complete injury. Nonetheless, prospective, randomized trials in larger cohorts are still needed.