Effect of spinal-pelvic sagittal balance on the clinical outcomes after lumbar fusion surgery.

BACKGROUND: Spinal-pelvic sagittal balance is important for maintaining energy-efficient posture in normal and diseased states.Few reports to date have evaluated the effect of spinal-pelvic sagittal balance on clinical outcomes after lumbar interbody fusion in patients with lumbar degenerative diseases (LDD). METHODS: A total of 303 patients treated with posterior lumbar interbody fusion surgery for lumbar degenerative disease from January 2012 to December 2019 were enrolled in this retrospective study according to the inclusion criteria. Preoperative and postoperative spinal-pelvic sagittal parameters including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) and lumbar lordosis (LL) of the patients were evaluated and compared. 163 patients whose postoperative PI-LL ≤ 10° were divided into the spinal-pelvic match group (Group M), while 140 patients were divided into the spinal-pelvic mismatch group (Group MM). Preoperative and postoperative Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) for back pain of both groups were compared. RESULTS: There was no significant difference between the two groups in demographic and surgical data, except for blood loss in surgery. LL, PI, PT and SS of the patients at final follow-up were all statistically different from the preoperative values in the two groups(P < 0.05). There was no significant difference in LL, PI, PT and SS between the two groups before surgery. At the final follow-up, LL, PI and PT differed significantly between the two groups(P < 0.05). Compared with the preoperative results, ODI and VAS of low back in both groups decreased significantly at the final follow-up (P < 0.05). Significant differences in VAS and ODI were found between the two groups at the final follow-up (P < 0.05). The improvement rates of VAS and ODI of Group M are both significantly higher than Group MM. Regression analysis showed that age and spinal-pelvic match had significant effects on the improvement of patients' low back pain at the final follow-up. CONCLUSIONS: lumbar interbody fusion can significantly improve the prognosis of patients with LDD. In terms of outcomes with an average follow-up time of more than 2 years, the spinal-pelvic match has a positive effect on patients' quality of life and the release of low back pain.

A urine extracellular vesicle circRNA classifier for detection of high-grade prostate cancer in patients with prostate-specific antigen 2-10 ng/mL at initial biopsy.

The aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n = 263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing circPDLIM5, circSCAF8, circPLXDC2, circSCAMP1, and circCCNT2), which was evaluated in two independent cohorts (n = 497, n = 505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting ≥ GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.

Repeated subarachnoid administrations of allogeneic human umbilical cord mesenchymal stem cells for spinal cord injury: a phase 1/2 pilot study.

BACKGROUND AIMS: Stem cell transplantation is a potential treatment for intractable spinal cord injury (SCI), and allogeneic human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate because of the advantages of immune privilege, paracrine effect, immunomodulatory function, convenient collection procedure and little ethical concern, and there is an urgent need to develop a safe and effective protocol regarding their clinical application. METHODS: A prospective, single-center, single-arm study in which subjects received four subarachnoid transplantations of hUC-MSCs (1 × 106 cells/kg) monthly and were seen in follow-up four times (1, 3, 6 and 12 months after final administration) was conducted. At each scheduled time point, safety and efficacy indicators were collected and analyzed accordingly. Adverse events (AEs) were used as a safety indicator. American Spinal Injury Association (ASIA) and SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) total scores at the fourth follow-up were determined as primary efficacy outcomes, whereas these two indicators at the remaining time points as well as scores of pinprick, light touch, motor and sphincter, muscle spasticity and spasm, autonomic system, bladder and bowel functions, residual urine volume (RUV) and magnetic resonance imaging (MRI) were secondary efficacy outcomes. Subgroup analysis of primary efficacy indicators was also performed. RESULTS: Safety and efficacy assessments were performed on 102 and 41 subjects, respectively. Mild AEs involving fever (14.1%), headache (4.2%), transient increase in muscle tension (1.6%) and dizziness (1.3%) were observed following hUC-MSC transplantation and resolved thoroughly after conservative treatments. There was no serious AE. ASIA and IANR-SCIFRS total scores revealed statistical increases when compared with the baselines at different time points during the study, mainly reflected in the improvement of pinprick, light touch, motor and sphincter scores. Moreover, subjects showed a continuous and remarkable decrease in muscle spasticity. Regarding muscle spasm, autonomic system, bladder and bowel functions, RUV and MRI, data/imaging at final follow-up showed significant improvements compared with those at first collection. Subgroup analysis found that hUC-MSC transplantation improved neurological functions regardless of injury characteristics, including level, severity and chronicity. CONCLUSIONS: The authors' present protocol demonstrates that intrathecal administration of' allogeneic hUC-MSCs at a dose of 106 cells/kg once a month for 4 months is safe and effective and leads to significant improvement in neurological dysfunction and recovery of quality of life.

Subarachnoid transplantation of human umbilical cord mesenchymal stem cell in rodent model with subacute incomplete spinal cord injury: Preclinical safety and efficacy study.

Functional multipotency renders human umbilical cord mesenchymal stem cell (hUC-MSC) a promising candidate for the treatment of spinal cord injury (SCI). However, its safety and efficacy have not been fully understood for clinical translation. In this study, we performed cellular, kinematic, physiological, and anatomical analyses, either in vitro or in vivo, to comprehensively evaluate the safety and efficacy associated with subarachnoid transplantation of hUC-MSCs in rats with subacute incomplete SCI. Concerning safety, hUC-MSCs were shown to have normal morphology, excellent viability, steady proliferation, typical biomarkers, stable karyotype in vitro, and no tumorigenicity both in vitro and in vivo. Following subarachnoid transplantation of hUC-MSCs in the subject rodents, the biodistribution of hUC-MSCs was restricted to the spinal cord, and no toxicity to immune system or organ function was observed. Body weight, organ weight, and the ratio of the latter upon the former between stem cell-transplanted rats and placebo-injected rats revealed no statistical differences. Regarding efficacy, hUC-MSCs could differentiate into osteoblasts, chondrocytes, adipocytes and neural progenitor cells in vitro. While in vivo studies revealed that subarachnoid transplantation of stem cells resulted in significant improvement in locomotion, earlier automatic micturition recovery and reduced lesion size, which correlated with increased regeneration of tracking fiber and reduced parenchymal inflammation. In vivo luminescence imaging showed that a few of the transplanted luciferase-labeled hUC-MSCs tended to migrate towards the lesion epicenter. Shortened latency and enhanced amplitude were also observed in both motor and sensory evoked potentials, indicating improved signal conduction in the damaged site. Immunofluorescent staining confirmed that a few of the administrated hUC-MSCs integrated into the spinal cord parenchyma and differentiated into astrocytes and oligodendrocytes, but not neurons. Moreover, decreased astrogliosis, increased remyelination, and neuron regeneration could be observed. To the best of our knowledge, this preclinical study provides detailed safety and efficacy evidence regarding intrathecal transplantation of hUC-MSCs in treating SCI for the first time and thus, supports its initiation in the following clinical trial.

Risk factor of contralateral radiculopathy following microendoscopy-assisted minimally invasive transforaminal lumbar interbody fusion.

PURPOSE: Microendoscopy-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is an advantageous method for treating lumbar degenerative disease; however, some patients show contralateral radiculopathy postoperatively. This study aims to investigate its risk factor. METHODS: A total of 130 cases who underwent microendoscopy-assisted MIS-TLIF at L4-5 level were divided into symptomatic and asymptomatic groups according to the presence of postoperative contralateral radiculopathy. Both preoperative and postoperative radiographic parameters, as well as their changes were compared between the two groups, including lumbar lordosis (LL), surgical segmental angle (SSA), disc height (DH), contralateral foramen area (CFA) and contralateral canal area (CCA). Screw breach on contralateral L4 pedicle and decompression method (ipsilateral or bilateral canal decompression through unilateral route) were also analyzed as potential risk factors. Receiver operating characteristic (ROC) curve was drawn for the risk factor to determine the optimal threshold for predicting postoperative contralateral radiculopathy. Besides, clinical outcome assessment, involving Visual Analog Score (VAS) for back and leg, Japanese Orthopaedics Association Score (JOA) and Oswestry Disability Index (ODI), was also compared between the two groups before surgery and at final follow-up (at least 3 months after the surgery for asymptomatic patients or final treatments of contralateral radiculopathy for symptomatic cases). RESULTS: Postoperative contralateral radiculopathy occurred in 11 (8.5%) of the 130 patients. Both preoperative and postoperative CFA as well as its change were significantly decreased in symptomatic group compared with asymptomatic group (all P < 0.05). For the remaining four parameters (LL, SSA, DH, CCA), their preoperative, postoperative and change values showed no statistical difference between the two groups (all P > 0.05). Neither screw breach nor decompression method revealed statistical association with this complication (both P > 0.05). Based on ROC curve, the optimal threshold of preoperative CFA was 0.76 cm2. At final follow-up, significant improvement in VAS (back and leg), JOA and ODI was observed in both groups compared with preoperative baseline (all P < 0.05), while no difference was found between the two groups (all P > 0.05). CONCLUSIONS: Preoperative contralateral foramen stenosis is the risk factor of contralateral radiculopathy following microendoscopy-assisted MIS-TLIF. If preoperative CFA at L4-5 level is not larger than 0.76 cm2, prophylactic measures, including both indirect and direct decompression of contralateral foramen, are recommended.

A MRI study of lumbar plexus with respect to the lateral transpsoas approach to the lumbar spine.

PURPOSE: To evaluate the relative position between lumbar plexus and access corridor of minimally invasive lateral transpsoas lumbar approach, as well as the approach safety. METHODS: Three-dimensional fast imaging employing steady-state acquisition (3D FIESTA) sequence images of lumbar spine were obtained from 58 patients with lumbar degenerative diseases for reconstruction to analyze the distribution of lumbar plexus from L1-L2 to L4-L5 level with respect to the transpsoas lumbar approach. The axial image distance (AID) between the anterior edge of lumbar plexus and the sagittal central perpendicular line (SCPL) of disc was measured. SCPL was drawn perpendicularly to the sagittal plane of intervertebral disc and it passed through its central point, which is initial dilator trajectory for transpsoas approach. As related to the SCPL of disc, the distance with a positive value was set to indicate neural tissue posterior to it, while anterior to it was represented by a negative value. RESULTS: In relation to SCPL of disc, the AID of lumbar plexus was measured 13.01 ± 1.70, 8.61 ± 2.26, 1.12 ± 2.37 and -5.42 ± 3.26 mm from L1-L2 to L4-L5 level, respectively, while the AID of genitofemoral nerve was recorded -1.13 ± 2.87, -5.78 ± 2.33 and -10.53 ± 3.30 mm from L2-L3 to L4-L5 level accordingly. CONCLUSION: With respect to the SCPL of disc, a trajectory of guide wire or a radiographic reference landmark to place working channel, lumbar plexus lies posteriorly to it from L1-L2 to L3-L4 level and shifts anteriorly to it at L4-L5 level, while genitofemoral nerve locates anteriorly to the SCPL from L2-L3 to L4-L5 level. Neural retraction may take place during sequential dilation of access corridor especially at L4-L5 level.

[Karyotype analysis using cells cultured from fetal bladder centesis].

OBJECTIVE: To explore the feasibility of karyotype analysis using cells cultured from fetal bladder centesis samples. METHODS: Samples were derived from fetal bladder centesis for 3 fetuses featuring giant bladder and oligohydramnios. Following in vitro culture, cells were routinely processed and stained for chromosome analysis. RESULTS: For all 3 cases, cell culture has achieved success. Sufficient metaphase cells were obtained for chromosome counting and karyotype analysis. The karyotypes of the 3 fetuses were respectively 46, XY, 46, XX, t(1;5)(q22;q12)[7]/46, XX[4], and 46, XY. CONCLUSION: Cells cultured from fetal bladder centesis may be used for karyotype analysis following in vitro culturing. This new approach can enable prenatal chromosome analysis for fetuses featuring smaller gestational weeks, giant bladder and oligohydramnios.

Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate for spinal cord injury (SCI) repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources. However, modest clinical efficacy hampered the progression of these cells to clinical translation. This discrepancy may be due to many variables, such as cell source, timing of implantation, route of administration, and relevant efficacious cell dose, which are critical factors that affect the efficacy of treatment of patients with SCI. Previously, we have evaluated the safety and efficacy of 4 × 106 hUC-MSCs/kg in the treatment of subacute SCI by intrathecal implantation in rat models. To search for a more accurate dose range for clinical translation, we compared the effects of three different doses of hUC-MSCs - low (0.25 × 106 cells/kg), medium (1 × 106 cells/kg) and high (4 × 106 cells/kg) - on subacute SCI repair through an elaborate combination of behavioral analyses, anatomical analyses, magnetic resonance imaging-diffusion tensor imaging (MRI-DTI), biotinylated dextran amine (BDA) tracing, electrophysiology, and quantification of mRNA levels of ion channels and neurotransmitter receptors. Our study demonstrated that the medium dose, but not the low dose, is as efficient as the high dose in producing the desired therapeutic outcomes. Furthermore, partial restoration of the γ-aminobutyric acid type A (GABAA) receptor expression by the effective doses indicates that GABAA receptors are possible candidates for therapeutic targeting of dormant relay pathways in injured spinal cord. Overall, this study revealed that intrathecal implantation of 1 × 106 hUC-MSCs/kg is an alternative approach for treating subacute SCI.

Comparative Efficacy and Safety of 11 Drugs as Therapies for Adults With Neuropathic Pain After Spinal Cord Injury: A Bayesian Network Analysis Based on 20 Randomized Controlled Trials.

Objective: To provide an updated analysis of the efficacy and safety of drugs for the management of neuropathic pain (NP) after spinal cord injury (SCI) based on Bayesian network analysis. Methods: A Bayesian network meta-analysis of literature searches within PubMed, Cochrane Library, Embase, and Web of Science databases from their inception to February 21 2021 was conducted without language restrictions. Paired and network meta-analyses of random effects were used to estimate the total standardized mean deviations (SMDs) and odds ratios (ORs). Results: A total of 1,133 citations were identified and 20 RCTs (including 1,198 patients) involving 11 drugs and placebos for post-SCI NP selected. The 5 outcomes from all 11 drugs and placebos had no inconsistencies after Bayesian network analysis. BTX-A gave the most effective pain relief for the 4 weeks, following a primary outcome. No significant differences were found among drugs with regard to adverse events of the primary outcome. Gabapentin, BTX-A, and pregabalin were found to be the most helpful in relieving secondary outcomes of mental or sleep-related symptoms with differences in SMDs, ranging from -0.63 to -0.86. Tramadol triggered more serious adverse events than any of the other drugs with differences in ORs ranging from 0.09 to 0.11. Conclusion: BTX-A, gabapentin, pregabalin, amitriptyline, ketamine, lamotrigine, and duloxetine were all effective for NP management following SCI. Lamotrigine and gabapentin caused fewer side effects and had better efficacy in relieving mental or sleep-related symptoms caused by SCI-related NP. Tramadol, levetiracetam, carbamazepine, and cannabinoids could not be recommended due to inferior safety or efficacy. Systematic Review Registration: [https://inplasy.com/inplasy-2020-7-0061/], identifier [INPLASY202070061].

[Biomechanical stability of unilateral pedicle screw fixation on cadaveric model simulated two-level posterior lumbar interbody fusion].

OBJECTIVE: To analyze the biomechanical efficacy of unilateral pedicle screw fixation on human cadaveric lumbar spine model simulated by two-level posterior lumbar interbody fusion (PLIF). METHODS: Six fresh-frozen adult human cadaveric lumbar spine motion segments (L(2)-S(2)) were simulated to unilateral/bilateral L(4)-S(1) PLIF constructs augmented by unilateral/bilateral pedicle screw fixation sequentially and respectively. All configurations were tested by MTS 858 in the following sequential construct order: the intact, UI (unilateral instability), UIUF1C (unilateral instability via unilateral pedicle screw fixation plus one cage), BIUF1C (bilateral instability via unilateral pedicle screw fixation plus one cage), BIBF1C (bilateral instability via bilateral pedicle screw fixation plus one cage) and BI (bilateral instability without pedicle screw and cage). Each specimen was nondestructively tested in flexion/extension, lateral bending, and axial rotation. An axial compressive load ranged from 40 N to 360 N and the maximum peak moment of 8 N·m was applied during testing. The range of motion (ROM) and neutral zone (NZ) of fusion segment were recorded by a 6-Eagle Motion Analysis F40 system, and then statistic comparison were performed between different simulated constructs with One Way of ANOVA and Post hoc LSD tests. RESULTS: BIBF1C had the lowest ROM and NZ of L(4)-S(1) fusion segments in all loading models, which were significantly lower than those of any uninstrumented construct (the intact, UI and BI) (P < 0.05). In flexion/extension, lateral bending, and axial rotation, the ROM of UIUF1C was respectively 2.53 ± 1.12, 4.03 ± 2.19, 2.78 ± 1.00 and the NZ of UIUF1C was respectively 1.14 ± 0.70, 1.96 ± 1.13, 1.28 ± 0.71, which were significantly lower than those of the intact (P < 0.05). Compared to BIBF1C, the ROM and NZ were respectively increased 60.13% and 17.52% in flexion/extension, 315.46% and 243.86% in lateral bending, 8.17% and 6.20% in axial rotation, however, there were no significant differences between these two constructs (P > 0.05). In lateral-bending and axial rotation, the ROM and NZ of BIUF1C were significantly higher than those of BIBF1C (P < 0.05). In flexion/extension, the ROM and NZ of BIUF1C were higher than those of BIBF1C but there were no significant differences (P > 0.05). Compared to the intact, BIUF1C had lower ROM and NZ except for higher NZ in axial rotation, and there were significant differences only in flexion/extension (P < 0.05). CONCLUSIONS: All tested two-level unilateral fixation on simulated human cadaveric model with unilateral PLIF can achieve similar initial biomechanical stability in comparison with two-level bilateral pedicle screw fixation. However in most test modes, two-level unilateral pedicle screw fixation on simulated human cadaveric model with bilateral PLIF can not achieve enough biomechanical efficacy in comparison with two-level bilateral pedicle screw fixation.

Human umbilical cord mesenchymal stem cells to treat spinal cord injury in the early chronic phase: study protocol for a prospective, multicenter, randomized, placebo-controlled, single-blinded clinical trial.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) support revascularization, inhibition of inflammation, regulation of apoptosis, and promotion of the release of beneficial factors. Thus, they are regarded as a promising candidate for the treatment of intractable spinal cord injury (SCI). Clinical studies on patients with early chronic SCI (from 2 months to 1 year post-injury), which is clinically common, are rare; therefore, we will conduct a prospective, multicenter, randomized, placebo-controlled, single-blinded clinical trial at the Third Affiliated Hospital of Sun Yat-sen University, West China Hospital of Sichuan University, and Shanghai East Hospital, Tongji University School of Medicine, China. The trial plans to recruit 66 early chronic SCI patients. Eligible patients will undergo randomization at a 2:1 ratio to two arms: the observation group and the control group. Subjects in the observation group will receive four intrathecal transplantations of stem cells, with a dosage of 1 × 106/kg, at one calendar month intervals. Subjects in the control group will receive intrathecal administrations of 10 mL sterile normal saline in place of the stem cell transplantations. Clinical safety will be assessed by the analysis of adverse events and laboratory tests. The American Spinal Injury Association (ASIA) total score will be the primary efficacy endpoint, and the secondary efficacy outcomes will be the following: ASIA impairment scale, International Association of Neural Restoration-Spinal Cord Injury Functional Rating Scale, muscle tension, electromyogram, cortical motor and cortical sensory evoked potentials, residual urine volume, magnetic resonance imaging-diffusion tensor imaging, T cell subtypes in serum, neurotrophic factors and inflammatory factors in both serum and cerebrospinal fluid. All evaluations will be performed at 1, 3, 6, and 12 months following the final intrathecal administration. During the entire study procedure, all adverse events will be reported as soon as they are noted. This trial is designed to evaluate the clinical safety and efficacy of subarachnoid transplantation of hUC-MSCs to treat early chronic SCI. Moreover, it will establish whether cytotherapy can ameliorate local hostile microenvironments, promote tracking fiber regeneration, and strengthen spinal conduction ability, thus improving overall motor, sensory, and micturition/defecation function in patients with early chronic SCI. This study was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University, China (approval No. [2018]-02) on March 30, 2018, and was registered with ClinicalTrials.gov (registration No. NCT03521323) on April 12, 2018. The revised trial protocol (protocol version 4.0) was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University, China (approval No. [2019]-10) on February 25, 2019, and released on ClinicalTrials.gov on April 29, 2019.

[Additional screws fixation on fractured vertebrae versus only short-segment posterior instrumentation for thoracolumbar A3 fracture without neurologic deficit].

OBJECTIVE: To compare the clinical results of additional screws fixation on fractured vertebrae versus only short-segment posterior transpedicular instrumentation for A3 thoracolumbar fracture without neurologic deficit. METHODS: Clinical data of 52 cases of thoracolumbar burst fracture without neurologic deficit were retrospectively analyzed. All patients were divided into 2 groups due to different instrumentation and all fractures were classified as type A3 according to AO Classification.From January 2005 to December 2006, 23 cases in group A were treated by short-segment posterior instrumentation combined with additional screws fixation on fractured vertebrae. There were 18 male and 5 female with a mean age of (35.3+/-8.3) years. The fracture segment included 1 in T11, 9 in T12, 11 in L1 and 2 in L2. From January 1999 to December 2004, 29 cases in group B were treated only by conventional short-segment posterior transpedicular instrumentation. There were 20 male and 9 female with a mean age of (37.3+/-6.8) years. The fracture segment included 1 in T11, 7 in T12, 20 in L1 and 1 in L2. The clinical effect and radiographic measurements were respectively compared preoperatively, immediate and 2 years postoperatively. RESULTS: All patients were followed up and the mean follow-up time was (37.4+/-10.9) months (from 24 to 48 months). There was no statistic difference of mean JOA and VAS score between 2 groups preoperatively, immediate and 2 years postoperatively (P>0.05). The average immediate postoperative correction of Cobb's angle was 13.7 degrees+/-7.7 degrees in group A, which was statistically significantly higher than that of 8.8 degrees+/-5.0 degrees in group B (P<0.01). The mean kyphosis correction loss of 2.9 degrees+/-1.5 degrees in group A was statistically significantly lower than that of 5.0 degrees+/-2.9 degrees in group B 2 years postoperatively (P<0.01). The average restoration of anterior height of fractured vertebral body immediate postoperatively was (29.4+/-6.0)% and (21.7+/-6.9)% respectively. The mean correction loss of anterior height 2 years postoperatively was (3.1+/-0.8)% and (6.6+/-3.0)% respectively. The average restoration of posterior height of fractured vertebral body immediate postoperatively was (8.5+/-3.2)% and (6.1+/-1.8)% respectively. The mean correction loss of posterior height 2 years postoperatively was (2.0+/-0.8)% and (3.4+/-1.0)% respectively. There were significant differences in average restoration of anterior/posterior height immediate postoperatively and correction loss of anterior/posterior height 2 years postoperatively between the 2 groups (P<0.01). According to fracture fragments protruded into the spinal canal on immediate postoperative CT image, there were complete reduction in 11 cases (47.8%) and partial reduction in 12 cases (52.2%) in group A, which was statistically significantly better than those in group B (P<0.01). There was no severe neurologic complications and no other complications related to additional screws fixation postoperatively. Pedicle screw breakage occurred in 2 cases in group B and none in group A. CONCLUSIONS: Better initial kyphosis correction and less loss of correction 2 years after operation can be obtained by using additional screws fixation on fractured vertebra for thoracolumbar A3 fracture without neurologic deficit.

Less Vertebral Bone Mass after Treatment with Macitentan in Mice: A Pilot Study.

PURPOSE: Blood vessels and skeleton interact together. Endothelin-1 is a potent vasoconstrictor and also has an effect on bone metabolism. The dual antagonist to both endothelin-1 type A and B receptors, Macitentan, has been approved for clinical management of pulmonary arterial hypertension while little is known about the secondary effect of the drug on spine. We aimed to answer how vertebral bone mass responded to Macitentan treatment in mice. METHODS: Sixteen male balb/c mice at 6 months were randomly assigned into 2 groups. Vehicle and Macitentan were administrated via intraperitoneal injection to Control group and Treatment group, respectively, for 4 months. At sacrifice, plasma endothelin-1 was evaluated with ELISA and vertebral bone mass was evaluated with Microcomputed Tomography and histological analysis. RESULTS: We found higher plasma endothelin-1 level (p<0.01) and less vertebral bone mass (p<0.05) in Treatment group compared to controls. Moreover, less osteoblasts and more osteoclasts were observed in the vertebral trabecular bone in the Treatment group compared to controls, by immunohistochemistry of the cell-specific markers. CONCLUSIONS: Treatment with Macitentan is associated with significant lower vertebral bone mass and therefore the secondary effect of dual antagonists to endothelin-1 receptors on the skeleton should be monitored and investigated in clinical practice. Both osteoblasts and osteoclasts may be involved while the molecular mechanism needs to be further explored.

Treatment of Single-Level Thoracic Tuberculosis by Percutaneous Endoscopic Débridement and Allograft via the Transforaminal Approach Combined with Percutaneous Pedicle Screw Fixation: A Multicenter Study with a Median Follow-Up of 36 Months.

OBJECTIVE: To examine effects of percutaneous endoscopic débridement and allograft via the transforaminal approach combined with percutaneous pedicle screw fixation as treatment for single-level thoracic tuberculosis. METHODS: This multicenter retrospective analysis included 75 patients with single-level thoracic tuberculosis who underwent percutaneous endoscopic débridement and allograft via the transforaminal approach combined with percutaneous pedicle screw fixation and were followed for >36 months between January 2012 and December 2014. RESULTS: Follow-up was 36-48 months (average 41.1 ± 2.2 months). Intraoperative blood loss was low (average 30.5 ± 7.9 mL), and bed rest time was short (average 1.5 ± 0.3 days). No recurrence was observed in all 75 patients. Except for 3 patients, almost all patients (96%) achieved grade I or II fusion in interbody bone grafting. Segmental Cobb angle was 13.5° ± 4.1° before surgery, 10.5° ± 3.7° immediately after surgery, and 11.7° ± 3.9° at 36 months of follow-up. All patients achieved complete recovery of neurologic function (American Spinal Injury Association grade E), including 15 patients with spinal cord injury (American Spinal Injury Association grade D) before surgery. The visual analog scale and 36-Item Short-Form Health Survey scores significantly improved at 1, 3, 12, and 36 months of follow-up. No complications related to internal fixation occurred within the follow-up period; complication rate was 9.0%. CONCLUSIONS: Median follow-up clinical experience with percutaneous endoscopic débridement and allograft via the transforaminal approach combined with percutaneous pedicle screw fixation indicates that the technique is safe, effective, feasible, and minimally invasive.

Spinal surgeons' learning curve for lumbar microendoscopic discectomy: a prospective study of our first 50 and latest 10 cases.

BACKGROUND: Microendoscopic discectomy (MED) is a minimally invasive operation that allows rapid recovery from surgery for lumbar disc herniation, but has replaced traditional open surgery in few hospitals because most surgeons avoid its long learning curve. We evaluated the effectiveness and safety of lumbar MED at stages of spinal surgeons' learning curve. METHODS: Fifty patients receiving MED from June 2002 to February 2003 were divided into chronological groups of ten each: A - E. The control group F was ten MED patients treated later by the same medical team (September - October 2006). All operations were performed by the same team of spinal surgeons with no MED experience before June 2002. We compared groups by operation time, blood loss, complications and need for open surgery after MED failure. RESULTS: Operation times by group were: A, (107 +/- 14) minutes; B, (85 +/- 13) minutes; C, (55 +/- 19) minutes; D, (52 +/- 12) minutes; E, (51 +/- 13) minutes; and F, (49+/- 15) minutes. Blood loss were: A, (131 +/- 73) ml; B, (75 +/- 20) ml; C, (48 +/- 16) ml; D, (44 +/- 17) ml; E, (45 +/- 18) ml; and F, (45 +/- 16) ml. Both operation time and blood loss in groups C, D, E and F were smaller and more stable compared with groups A and B. Japanese Orthopedic Association assessment (JOA) score of each group in improvement rate immediately and one year after operation were as follows (in percentage): A, (79.8 +/- 8.8)/(89.8 +/- 7.7); B, (78.6 +/- 8.5)/(88.5 +/- 7.8); C, (80.8 +/- 11.3)/(90.8 +/- 6.7); D, (77.7 +/- 11.4)/(88.9 +/- 9.3); E, (84.0 +/- 8.7)/(89.6 +/- 9.0); and F, (77.8 +/- 11.6)/(86.9 +/- 8.4). Groups showed no statistical difference in improvement rates. Complications developed in three patients in group A, two in group B, and none in the other groups. CONCLUSIONS: Spinal surgeons performing MED become proficient after 10 - 20 operations, when their skill becomes fairly sophisticated. Patients' improvement rate is the same regardless of surgeons' phase of learning curve.

Concurrent arthroscopic bicruciate ligament reconstruction using Achilles tendon-bone allografts: experience with 15 cases.

OBJECTIVE: To evaluate the clinical outcome of arthroscopically assisted combined anterior and posterior cruciate ligament (ACL/PCL) reconstructions using Achilles tendon-bone allografts. METHODS: Associated meniscus injuries were treated according to established methods prior to ligament reconstructions during arthroscopic surgery. Thirty Achilles tendon-bone allografts were used to reconstruct torn ACL and PCL in 15 knees. At postoperative follow-up, all knees were graded using the modified IKDC and the Lysholm scoring systems just as done preoperatively. RESULTS: were analyzed compared with the contralateral healthy knees. Results: Eleven men and 4 women with a minimum of 3-year follow-up (mean 38 months) were included in the study. Preoperatively, the group ratings by the modified IKDC standards were all severely abnormal. Twelve bicruciate reconstructions were performed in subacute or chronic stage (larger than 3-8 weeks), 3 for acute ligamentous deficiencies (less than or equal to 3 weeks). The noticeable early complication was transitory local fever combined with joint effusion in one case. At postoperative follow-up, 9 knees were normal, 5 nearly normal and 1 abnormal. On Lysholm score the difference was statistically significant (t- test, P less than 0.001) before and after operation. CONCLUSIONS: Achilles tendon-bone allograft offers an alternative for simultaneous arthroscopic ACL/PCL reconstructions. However, further investigation is needed to eradicate its potential immunogenicity for better use.

Microendoscopy-Assisted Minimally Invasive Versus Open Transforaminal Lumbar Interbody Fusion for Lumbar Degenerative Diseases: 5-Year Outcomes.

OBJECTIVE: We sought to evaluate 5-year outcomes between microendoscopy-assisted minimally invasive (MIS) and open transforaminal lumbar interbody fusion (TLIF). METHODS: Sixty single-level MIS and open surgeries were performed (30 patients in either group). Perioperative parameters including operative duration, intraoperative estimated blood loss, fluoroscopy time, postoperative analgesic usage, ambulatory time, and complications were recorded. Visual analog scale (back and leg), Japanese Orthopaedics Association score, and Oswestry Disability Index were obtained. Finally, self-evaluation of surgical outcomes (modified MacNab criteria), interbody fusion rate (Bridwell grade 1), and prevalence of adjacent segment degeneration were assessed. RESULTS: Intraoperative estimated blood loss and postoperative analgesia usage were reduced in the MIS group, and patients undergoing microendoscopy-assisted MIS-TLIF ambulated earlier than those receiving open TLIF postoperatively. Nevertheless, surgical duration and fluoroscopy time were prolonged in the MIS group. Complication incidences were similar in both groups. Visual analog scale (back and leg), Japanese Orthopaedics Association, and Oswestry Disability Index were improved at 1 month, 2 years, and 5 years postoperatively in both groups when compared with preoperative scores. Significant improvements in these scores were found in the MIS group at 1 month postoperatively, while at 2 years and 5 years postoperatively, both groups revealed comparable aforementioned scores. Excellent and perfect scale rating, interbody fusion rate, and adjacent segment degeneration prevalence between the groups were almost similar. CONCLUSIONS: Microendoscopy-assisted MIS-TLIF is comparable with open TLIF in terms of 5-year outcomes with additional benefits of reduced intraoperative iatrogenic injury, decreased initial pain, minimized activity restrictions, and accelerated ambulation recovery after surgery.

Foraminoplasty at the Tip or Base of the Superior Articular Process for Lateral Recess Stenosis in Percutaneous Endoscopic Lumbar Discectomy: A Multicenter, Retrospective, Controlled Study with 2-Year Follow-Up.

OBJECTIVE: To compare the clinical efficacy and complications which obtained foraminoplasty at the tip or base of the superior articular process (SAP) for the patients with lateral recess stenosis treated by percutaneous endoscopic lumbar discectomy (PELD). METHODS: Between January 2015 and January 2016, 156 patients of lumbar disc herniation accompanying with lateral recess stenosis were treated with PELD in five tertiary hospitals and fulfilled the 2-year follow-up. Among them, 78 patients obtained a foraminoplasty at the tip of SAP (group A), and foraminoplasty at the base of SAP was performed in the other 78 cases (group B). Clinical efficacy was evaluated using the visual analog scale (VAS) score for back and leg pain, Oswestry Disability Index (ODI), and 36-item Short-Form Health Survey (SF-36) score. The intervals of follow-up were scheduled at 1 month, 3 months, 6 months, 1 year, and 2 years after surgery. RESULTS: Mean operative duration is shorter in group B (55 versus 61 min, P = 0.047). Only one case belonged to group A could not tolerate the neural irritation and required conversion to an open procedure. During the surgery, no dura tears, cauda equina syndrome, or infections were observed. 5 patients experienced transient dysesthesia located at the exiting nerve in group A, while no cases complained dysesthesia in group B. 2 cases who suffered temporary motor weakness all belonged to group A. A total of 5 cases obtained a revision surgery after recurrence in the follow-up, in which 3 patients belonged to group A. Compared to the preoperative data, significant improvements in VAS scores of low back pain and sciatica, ODI, and SF-36 PCS and MC were observed in the follow-up, respectively (P < 0.05, respectively). However, no statistical difference was observed at all time-points after surgery between these two groups (P > 0.05, respectively). CONCLUSIONS: For the patients of LDH accompanying with lateral recess stenosis, compared with the routine foraminoplasty at the tip of SAP, our modified foraminoplastic technique does not only change place of foraminoplasty to the base of SAP but also simplified puncture process in transforaminal PELD. Although there was no significant difference in symptom relief, the modified foraminoplasty showed the advantages in decreasing the incidence of postoperative neural dysfunction and reducing operation time.

Perineurium-like sheath derived from long-term surviving mesenchymal stem cells confers nerve protection to the injured spinal cord.

The functional multipotency enables mesenchymal stem cells (MSCs) promising translational potentials in treating spinal cord injury (SCI). Yet the fate of MSCs grafted into the injured spinal cord has not been fully elucidated even in preclinical studies, rendering concerns of their safety and genuine efficacy. Here we used a rat spinal cord transection model to evaluate the cell fate of allograft bone marrow derived MSCs. With the application of immunosuppressant, donor cells, delivered by biocompatible scaffold, survived up to 8 weeks post-grafting. Discernible tubes formed by MSCs were observed beginning 2 weeks after transplantation and they dominated the morphological features of implanted MSCs at 8 weeks post-grafting. The results of immunocytochemistry and transmission electron microscopy displayed the formation of perineurium-like sheath by donor cells, which, in a manner comparable to the perineurium in peripheral nerve, enwrapped host myelins and axons. The MSC-derived perineurium-like sheath secreted a group of trophic factors and permissive extracellular matrix, and served as a physical and chemical barrier to insulate the inner nerve fibers from ambient oxidative insults by the secretion of soluble antioxidant, superoxide dismutase-3 (SOD3). As a result, many intact regenerating axons were preserved in the injury/graft site following the forming of perineurium-like sheath. A parallel study utilizing a good manufacturing practice (GMP) grade human umbilical cord-derived MSCs or allogenic MSCs in an acute contusive/compressive SCI model exhibited a similar perineurium-like sheath formed by surviving donor cells in rat spinal cord at 3 weeks post-grafting. The present study for the first time provides an unambiguous morphological evidence of perineurium-like sheath formed by transplanted MSCs and a novel therapeutic mechanism of MSCs in treating SCI.

Serum Osteocalcin and Testosterone Concentrations in Adult Males with or without Primary Osteoporosis: A Meta-Analysis.

Osteocalcin (Ocn) and testosterone play important roles in male skeleton. However, the concentrations of serum osteocalcin and testosterone have never been systematically compared between populations with and without primary male osteoporosis, a common skeletal disorder in adult males. We searched the PubMed, Embase, and Cochrane Library for relevant studies. A meta-analysis was performed to compare the serum osteocalcin and testosterone concentrations between primary osteoporotic males and age-matched nonosteoporotic (non-OP) males. Five case-control studies with 300 adult males were included. We found no significant difference between cases and controls in serum total osteocalcin (TOcn) [95% confidence interval (CI): -1.25, 1.31; p = 0.96] and total testosterone (TT) concentrations [95% CI: -0.88, 4.22; p = 0.20]. The level of evidence of this carefully performed meta-analysis is 3a according to Oxford (UK) CEBM Levels of Evidence. Future well-designed studies with larger sample size and better standardization of Ocn assay are awaited to confirm and update our current findings.