ELAVL2 loss promotes aggressive mesenchymal transition in glioblastoma.

Glioblastoma (GBM), the most lethal primary brain cancer, exhibits intratumoral heterogeneity and molecular plasticity, posing challenges for effective treatment. Despite this, the regulatory mechanisms underlying such plasticity, particularly mesenchymal (MES) transition, remain poorly understood. In this study, we elucidate the role of the RNA-binding protein ELAVL2 in regulating aggressive MES transformation in GBM. We found that ELAVL2 is most frequently deleted in GBM compared to other cancers and associated with distinct clinical and molecular features. Transcriptomic analysis revealed that ELAVL2-mediated alterations correspond to specific GBM subtype signatures. Notably, ELAVL2 expression negatively correlated with epithelial-to-mesenchymal transition (EMT)-related genes, and its loss promoted MES process and chemo-resistance in GBM cells, whereas ELAVL2 overexpression exerted the opposite effect. Further investigation via tissue microarray analysis demonstrated that high ELAVL2 protein expression confers a favorable survival outcome in GBM patients. Mechanistically, ELAVL2 was shown to directly bind to the transcripts of EMT-inhibitory molecules, SH3GL3 and DNM3, modulating their mRNA stability, potentially through an m6A-dependent mechanism. In summary, our findings identify ELAVL2 as a critical tumor suppressor and mRNA stabilizer that regulates MES transition in GBM, underscoring its role in transcriptomic plasticity and glioma progression.

Longitudinal clinical outcomes after full-endoscopic lumbar discectomy for recurrent disc herniation after open discectomy.

OBJECTIVE: Full-endoscopic lumbar discectomy (FELD) is a minimally invasive surgical option for recurrent lumbar disc herniation (LDH). Nonetheless, patients' clinical outcomes may be poorer after surgery for recurrent LDH than for primary LDH. Therefore, we compared patients' longitudinal clinical outcomes after FELD for recurrent LDH or primary LDH. METHODS: The medical records of patients who underwent FELD for primary LDH (group A) or recurrent LDH (group B) were retrospectively reviewed. The inclusion criteria were: 1) single-level LDH or recurrent LDH at L4-5 or L5-S1, 2) age ≤60 years, 3) previous open discectomy (group B), and 4) ≥6 months of follow-up. In total, 244 patients (group A, 211; group B, 33) were included. Clinical outcomes (Oswestry Disability Index [ODI]; visual analogue pain score for the back and leg [VAS-B] and [VAS-L]) over 24 months of follow-up were compared between groups with a linear mixed-effects model. RESULTS: All clinical outcomes significantly improved from pre-operation to 3 months postoperatively (p < 0.01), and the improvement was maintained for 24 months postoperatively in both groups. The clinical outcomes of groups A and B were not significantly different during 24 months follow-up (ODI, p = 0.94; VAS-B, p = 0.11; and VAS-L, p = 0.48). The reoperation rate was 3.3% in group A and 3.0% in group B, but the overall complication rate was higher in group B (9.8%) than in group A (6.6%). CONCLUSION: The longitudinal clinical outcomes after FELD for recurrent LDH may not be poor as feared. However, the higher complication rate in patients undergoing FELD for recurrent LDH should be noted.

The Efficacy of Ultrasonic Bone Scalpel for Unilateral Cervical Open-Door Laminoplasty: A Randomized Controlled Trial.

BACKGROUND: In cervical open-door laminoplasty for cervical myelopathy, a high-speed rotatory drill and rongeurs are used to make unicortical troughs and bicortical openings in the laminae. The lamina is reflected at the trough to enlarge the spinal canal, followed by bone healing on the hinge side to stabilize laminoplasty. The ultrasonic bone scalpel (UBS) has been used due to theoretical advantages including a better hinge union rate, less soft tissue trauma, less neurological injury, and shorter operative time. OBJECTIVE: To assess the superiority of UBS for hinge union compared to the drill through randomized controlled trial. METHODS: In 190 randomly allocated cervical myelopathy patients, the trough and opening at the lamina were made using either the drill (n = 95) or UBS (n = 95) during 2015 to 2018. The primary outcome was the hinge union rate on 6-mo postoperative computed tomography. Secondary outcomes included the hinge union rate at 12 mo, the operative time, intraoperative/postoperative bleeding, neurological injury, complications, and clinical outcomes over a 24-mo follow-up. RESULTS: Hinge union in all laminae was achieved in 60.0% (drill) and 43.9% (UBS) of patients at 6 mo (intention-to-treat analysis; P = .02; odds ratio, 2.1) and in 91.9% (drill) and 86.5% (UBS) at 12 mo. Dural injury only occurred in the drill group (2.1%), and the UBS group showed significantly less intraoperative bleeding (P < .01). The other secondary outcomes did not differ between groups. CONCLUSION: The hinge union rate was inferior in the UBS group at 6 mo postoperatively, but UBS was efficacious in reducing dural injuries and bleeding.

Does Preservation of Ligamentum Flavum in Percutaneous Endoscopic Lumbar Interlaminar Discectomy Improve Clinical Outcomes?

OBJECTIVE: Ligamentum flavum (LF) is an important anatomical structure for prevention of postoperative adhesions, but the opening of LF is necessary for percutaneous endoscopic lumbar interlaminar discectomy (PEID). Although the defect in LF is small with conventional PEID, the defect could be minimized with LF splitting technique. The objective of this study was to compare clinical outcomes of PEID with opening of LF versus splitting of LF. METHODS: A retrospective study was performed for patients underwent PEID for L5-S1. PEID with the opening of LF (open-group) was performed for 55 patients and with splitting of LF (split-group) was performed for 34 patients. The defect of LF in Open-group was 3-5 mm, but the defect was negligible in split-group because the split LF was reapproximated by its elasticity. Clinical outcomes were evaluated with Korean version of the Oswestry Disability Index (K-ODI) and visual analogue pain scores for back (VASB) and leg (VASL). The changes of clinical outcomes during postoperative 24 months between groups were evaluated with linear mixed-effects model. RESULTS: The clinical outcomes were similar between groups for K-ODI (p=0.98), VASB (p=0.52), and VASL (p=0.59). Each outcome demonstrated significant improvement from preoperative baseline throughout the postoperative 24 months (p<0.05). Complications included recurrence in 4 patients and dural tear in 1 in open-group (9.1%), and residual disc herniation in 2 patients and transient weakness in 1 in split-group (8.8%). CONCLUSION: Splitting versus opening LF in PEID may be left to the surgeon's discretion. The potential risks and benefits of LF handling should be considered when performing this surgical technique in PEID.

Postoperative Changes in Moderate to Severe Nonspecific Low Back Pain After Cervical Myelopathy Surgery.

OBJECTIVE: Cervical myelopathy patients sometimes experience concurrent nonspecific moderate to severe low back pain (msLBP). However, postoperative changes in msLBP after cervical myelopathy surgery have rarely been reported. Awareness of postoperative changes in msLBP may be helpful in consultation. Therefore, the objective of this study was to examine postoperative changes in msLBP. METHODS: Patients with cervical myelopathy and msLBP (a visual analog pain score ≥5/10) were reviewed prospectively, and 53 patients (male:female ratio, 28:25; mean age, 63.1 years) were enrolled. Cervical myelopathy was assessed with the Japanese Orthopedic Association score. Cervical laminoplasty was performed in 49 patients, and anterior cervical discectomy and fusion were performed in 4 patients. The patients were followed up postoperatively at 1, 3, 6, and 12 months and yearly thereafter. The primary endpoint was improvement of the visual analog scale score for back pain (VAS-B) by greater than 2.6/10. Prognostic factors were analyzed postoperatively at 12 months. The mean follow-up period was 16 ± 9 months. RESULTS: MsLBP improved in 58%, 49%, 53%, 52%, and 59% of the patients at 1, 3, 6, 12, and 24 months postoperatively, respectively. The VAS-B worsened after improvement or vice versa in approximately 30% of the patients during the follow-up period. Lumbar decompression operations were performed in 5 patients at 4, 6, 7, 15, and 16 months postoperatively. The recovery rate of the JOA score was a positive prognostic factor. CONCLUSIONS: Although the exact pathophysiology was not demonstrated, cervical myelopathy surgery may directly and indirectly improve msLBP.

The Recovery of Motor Strength after Posterior Percutaneous Endoscopic Cervical Foraminotomy and Discectomy.

OBJECTIVE: Cervical radiculopathy infrequently presents with motor weakness. Motor weakness was improved in >90% of patients after anterior cervical discectomy and fusion or posterior cervical foraminotomy. Posterior percutaneous endoscopic cervical foraminotomy and discectomy (PECF) is an alternative surgical technique, but the outcome of motor weakness has not been reported. Our objective was to demonstrate the longitudinal outcomes of motor weakness after PECF. METHODS: A retrospective review of 106 consecutive patients was performed. Preoperative motor weakness was graded as mild (IV/V strength) or severe (less than III/V strength). The patients visited the outpatient clinic at 1, 3, 6, and 12 months after surgery and yearly thereafter. Improvement was defined as an improved weakness of more than 1 grade, and normalization was defined as the recovery of complete motor strength. RESULTS: Motor weakness preoperatively presented in 76 of 106 (72%) patients (49%, mild weakness; 23%, severe weakness). After PECF, the weakness improved in 72 of 76 (95%) patients and normalized in 65 of 76 (86%) patients. In the patients with mild weakness, the normalization rates were 48%, 81%, 90%, and 96% at postoperative months 1, 3, 6, and 12, respectively. In the patients with severe weakness, the improvement rates were 50%, 71%, 83%, 88%, and 92%, and the normalization rates were 8%, 38%, 58%, 58%, and 63% at postoperative months 1, 3, 6, 12, and 24, respectively. CONCLUSIONS: Preoperative motor weakness was improved in 95% of the patients after PECF, but motor weakness was not normalized in 37% of the patients with severe weakness.