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].

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.

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.

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.

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.

Microendoscopy-assisted minimally invasive transforaminal lumbar interbody fusion for lumbar degenerative disease: short-term and medium-term outcomes.

OBJECTIVE: To evaluate short-term and medium-term outcomes of microendoscopy-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and open TLIF for lumbar degenerative disease. METHODS: In this prospective, randomized control study, 50 cases received microendoscopy-assisted MIS-TLIF (MIS group), while another well-matched 50 cases accepted open TLIF (open group). Parameters between both groups, including surgical duration, intraoperative blood loss and radiologic exposure, postoperative analgesic usage and ambulatory time, visual analogue scale (VAS) for back and leg, functional scores, self-evaluation of surgical outcome (modified MacNab criteria), interbody fusion rate, adjacent segment degeneration (ASD) rate, as well as complication incidence were compared at 1 month and 24 months postoperatively. RESULTS: Intraoperative blood loss and postoperative analgesic usage were significantly reduced in MIS group (P<0.05). Patients undergoing microendoscopy-assisted MIS-TLIF were able to ambulate earlier postoperatively than those receiving open TLIF (P<0.05). However, it showed prolonged surgical duration and enhanced radiologic exposure in MIS group (P<0.05). At 1 month postoperatively, MIS group was associated with more improvement of VAS and functional scores compared with open group (P<0.05). While at 24 months postoperatively, both groups revealed similar VAS and functional scores (P>0.05). Excellent and perfect scale rating by modified MacNab criteria, interbody fusion rate, ASD rate and complication incidence between both groups were nearly the same (P>0.05). CONCLUSIONS: Microendoscopy-assisted MIS-TLIF owns advantages of less iatrogenic injury, decreased blood loss, reduced analgesic usage and earlier rehabilitation, while it has drawbacks of more surgical duration and radiologic exposure. It is superior than open TLIF in terms of short-term clinical outcomes and has similar medium-term clinical outcomes.

Prospective evaluation of preoperative concerns for Chinese patients with spinal degenerative disease.

Objective of this study is to analyze preoperative concerns of patients suffering from spinal degenerative disease in a Chinese population. A total of 94 patients with spinal degenerative disease were included, and they were divided into four groups: male and female group, older (≥60 year-old) and younger group (<60 year-old). Questionnaire was designed through patients counseling, preliminary formulation, pilot test and final revision. Each patient was required to select three items of greatest concern. "Attention rate" (AR) was defined as ratio of selected times of one item upon case number within the group. AR of three most concerned items between male and female group, as well as older and younger group were compared and analyzed. All participants selected "recurrence of symptoms following operation" (41/94), "clinical outcome" (35/94) and "postoperative rehabilitation and daily activity" (30/94) as their three top items of concern. Both male and female groups selected "recurrence of symptoms following operation" (22/47, 19/47), "clinical outcome" (21/47, 14/47), "postoperative rehabilitation and daily activity" (15/47, 15/47) and "limb paralysis" (13/47, 14/47) as their most concerned items, revealing no statistical difference (P>0.05). Older group chose "clinical outcome" (17/46) as their most concerned item, followed by "limb paralysis" (14/46), "postoperative rehabilitation and daily activity" (14/46) and "recurrence of symptoms following operation" (12/46). Younger group chose "recurrence of symptoms following operation" (29/48), "clinical outcome" (18/48) and "postoperative rehabilitation and daily activity" (16/48) as their three top concerned items. AR of "recurrence of symptoms following operation" between older and younger group demonstrated statistical difference (P<0.001), while AR of remaining items of greatest concern between both groups were not statistically different (P>0.05). For Chinese patients, high level concerns are associated with surgical outcome and most of them reveal no gender-associated or age-associated difference. Assessing preoperative concerns empowers better preoperative counseling between surgeons and patients and more informed decision for patients.

Aberrant methylation of CDH13 is a potential biomarker for predicting the recurrence and progression of non muscle invasive bladder cancer.

BACKGROUND: CDH13 is a novel tumor suppressor gene often inactivated by aberrant promoter methylation in human cancers. Previous studies have shown that CDH13 methylation correlated with advanced disease and poor prognosis in non-muscle invasive bladder cancer (NMIBC). The aim of the current study was to investigate the correlations between CDH13 methylation and disease recurrence as well as progression of NMIBC. MATERIAL AND METHODS: The methylation status of CDH13 in 178 NMIBC samples and 38 normal bladder epithelial tissues was examined by methylation-specific PCR (MSP), and then correlated with clinicopathological features. RESULTS: We found that CDH13 methylation occurs frequently in NMIBC, and significantly correlates with high grade, advanced stage, larger tumor size, and tumor recurrence and progression. Moreover, patients with methylated CDH13 exhibited significantly shorter recurrence-free survival (P<0.0001) and progression-free survival (P=0.0060) than patients with unmethylated CDH13. In addition, a multivariate Cox proportional hazard model analysis suggests that CDH13 methylation is an independent predictor for the recurrence (P=0.0043) and progression (P=0.0016) of NMIBC after initial transurethral resection. CONCLUSIONS: Our findings demonstrate that CDH13 methylation is a frequent event in NMIBC, and is associated with unfavorable tumor features. It should be used as an independent predictor for the recurrence and progression of NMIBC, and may be useful for the design of individualized therapeutic modalities.

Aberrant methylation of protocadherin 17 and its clinical significance in patients with prostate cancer after radical prostatectomy.

BACKGROUND: Aberrant methylation of protocadherin 17 (PCDH17) has been reported in several human cancers. However, the methylation status of PCDH17 in prostate cancer and its clinical significance remains unclear. The aim of this study was to investigate the methylation status of PCDH17 and its clinical significance in patients with prostate cancer after radical prostatectomy. MATERIAL/METHODS: The methylation status of PCDH17 in 152 prostate cancer tissues and 51 non-tumoral prostate tissues was examined by methylation-specific PCR (MSP). Then the association between PCDH17 methylation and clinicopathologic parameters was analyzed. Kaplan-Meier survival analysis, log-rank test and multivariate Cox proportional hazard model analysis were used to analyze the correlation between PCDH17 methylation and prognosis of patients with prostate cancer. RESULTS: Our data demonstrated that PCDH17 methylation occurred frequently in prostate cancer. PCDH17 methylation was significantly associated with higher pathological Gleason score (P=0.0315), advanced pathological stage (P=0.0260), higher level of preoperative PSA (P=0.0354), positive angiolymphatic invasion (P=0.0461), positive lymph node metastasis (P=0.0362), and biochemical recurrence (BCR) (P=0.0018). In addition, PCDH17 methylation was an independent predictor of poor biochemical recurrence-free (BCR-free) survival and overall survival for patients with prostate cancer. CONCLUSIONS: PCDH17 methylation is a frequent tumor-specific event in prostate cancer, and is significantly correlated with shorter BCR-free survival and overall survival of patients with prostate cancer after radical prostatectomy. PCDH17 methylation in tumor samples after radical prostatectomy may be used as an independent prognostic biomarker.

Aberrant methylation of PCDH10 predicts worse biochemical recurrence-free survival in patients with prostate cancer after radical prostatectomy.

BACKGROUND: Prostate cancer is a common malignancy in men, and inevitably some patients experience biochemical recurrence after radical prostatectomy. To date, there are no reliable predictors for prostate cancer recurrence, and novel predictors are urgently needed. PCDH10 (protocadherin-10) is a novel tumor suppressor gene, which is down-regulated by promoter methylation in prostate cancer. The aim of this study was to evaluate the feasibility of using PCDH10 methylation to predict the biochemical recurrence (BCR) of prostate cancer after radical prostatectomy. MATERIAL/METHODS: Fresh tissue samples were obtained from 151 patients with primary prostate cancer, and from 34 patients with benign prostatic hyperplasia (BPH) as control. The methylation status of PCDH10 in prostate cancer tissues and controls were examined using methylation-specific PCR (MSP), and then associated with clinicopathological features and BCR-free survival of patients with prostate cancer. RESULTS: We found that PCDH10 methylation was detected in 79 (52.3%) patients with prostate cancer, but no methylation was found in controls (P<0.0001). Moreover, PCDH10 methylation was significantly associated with higher preoperative prostate-specific antigen (PSA) level (P <0.0001), higher Gleason Score (P<0.0001), advanced clinical stage (P=0.0002), lymph node metastasis (P=0.0389), angiolymphatic invasion (P=0.0303), and biochemical recurrence (P=0.0068). Moreover, PCDH10 methylation was associated with poor BCR-free survival (P<0.0001), and may be used as an independent predictor of BCR-free survival (P=0.0046). CONCLUSIONS: Our results indicate that PCDH10 methylation in prostate cancer tissue is an independent prognostic biomarker of worse BCR-free survival of patients with prostate cancer after radical prostatectomy.

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.