Safety and Efficacy of Local Steroid Application on Dysphagia Following Anterior Cervical Discectomy and Fusion: A Systematic Review and Meta-analysis.

STUDY DESIGN: A systematic review and meta-analysis. OBJECTIVE: To evaluate the safety and efficacy of local steroid application (LSA) on dysphagia after anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Dysphagia is one of the most common adverse events in the early postoperative period of ACDF. LSA is reported as an effective method to reduce the swelling of soft tissues, thereby decreasing the incidence of dysphagia. However, the safety and efficacy of LSA on dysphagia after ACDF need to be systematically reviewed and analyzed. METHODS: A comprehensive literature search was carried out in the database PubMed, Web of Science, EMBASE, Clinical key, Cochrane library, and Wiley Online Library to screen papers that report LSA in ACDF surgery. The Cochrane Collaboration tool and a methodological index for nonrandomized studies were used for the assessment of study quality. Data were analyzed with the Review Manager 5.3 software. RESULTS: A total of 10 studies were included. The results revealed no significant differences between the steroid group and the control group in ACDF regarding postoperative drainage, estimated blood loss, and neck disability index score ( P > 0.05). LSA significantly alleviates visual analog scale score for neck pain (or odynophagia) ( P < 0.05), reduces the length of hospital stay (weighted mean difference, -1.00 (-1.05 to -0.95); P < 0.001), and mitigates dysphagia rate and prevertebral soft-tissue swelling in the early postoperative period ( P < 0.05). There seemed to be no significant increase in the complication rate and steroid-related adverse events in the steroid group compared with the control group ( P < 0.05). CONCLUSIONS: LSA shows advantages in reducing the length of hospital stay, decreasing dysphagia rate, and mitigating prevertebral soft-tissue swelling in the early postoperative period of ACDF. Further large-scale studies are urgently required for the development of a standard protocol for LSA and further analysis of potential delay complications.

Influence of the facet joint angle on facet joint degeneration following pedicle screw fixation without fusion in thoracolumbar fractures.

BACKGROUND: Posterior approach pedicle screw fixation without fusion is widely used in the treatment of neurologically intact type A3 thoracolumbar fractures. OBJECTIVE: To analyze the influence of the facet joint (FJ) angle on FJ degeneration following posterior approach pedicle screw fixation without fusion in neurologically intact type A3 thoracolumbar fractures. METHODS: Fifty-eight patients who underwent pedicle screw fixation via the traditional posterior approach (n= 28) or the Wiltse approach (n= 30) were enrolled. A CT scan was performed before fixation and before fixation removal (Within 1.5 to 2 years after fixation) to evaluate the FJs parameters, including FJ inclination (FJI), FJ tropism (FJT), FJ violation, and FJ degeneration grade (FJDG), of three fixed segments and the adjacent segment below the fixed segments. RESULTS: There was no significant difference in FJ violation rate, FJDG deterioration, or FJ angle between the two groups (P> 0.05). FJDG deterioration showed a weak positive correlation with FJI and FJT before fixation, and the angular change in FJI (P< 0.05); and FJT before fixation and the angular change in FJI were risk factors for FJDG deterioration (P< 0.01). CONCLUSION: The Wiltse approach did not increase the rate of FJDG deterioration and FJs angle changes. However, the FJT before fixation and the angular change in FJI were risk factors for FJDG deterioration.

Quercetin ameliorates oxidative stress-induced senescence in rat nucleus pulposus-derived mesenchymal stem cells via the miR-34a-5p/SIRT1 axis.

BACKGROUND: Intervertebral disc degeneration (IDD) is a main contributor to low back pain. Oxidative stress, which is highly associated with the progression of IDD, increases senescence of nucleus pulposus-derived mesenchymal stem cells (NPMSCs) and weakens the differentiation ability of NPMSCs in degenerated intervertebral discs (IVDs). Quercetin (Que) has been demonstrated to reduce oxidative stress in diverse degenerative diseases. AIM: To investigate the role of Que in oxidative stress-induced NPMSC damage and to elucidate the underlying mechanism. METHODS: In vitro, NPMSCs were isolated from rat tails. Senescence-associated ß-galactosidase (SA-ß-Gal) staining, cell cycle, reactive oxygen species (ROS), real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, and western blot analyses were used to evaluated the protective effects of Que. Meanwhile the relationship between miR-34a-5p and Sirtuins 1 (SIRT1) was evaluated by dual-luciferase reporter assay. To explore whether Que modulates tert-butyl hydroperoxide (TBHP)-induced senescence of NPMSCs via the miR-34a-5p/SIRT1 pathway, we used adenovirus vectors to overexpress and downregulate the expression of miR-34a-5p and used SIRT1 siRNA to knockdown SIRT1 expression. In vivo, a puncture-induced rat IDD model was constructed, and X rays and histological analysis were used to assess whether Que could alleviate IDD in vivo. RESULTS: We found that TBHP can cause NPMSCs senescence changes, such as reduced cell proliferation ability, increased SA-ß-Gal activity, cell cycle arrest, the accumulation of ROS, and increased expression of senescence-related proteins. While abovementioned senescence indicators were significantly alleviated by Que treatment. Que decreased the expression levels of senescence-related proteins (p16, p21, and p53) and senescence-associated secreted phenotype (SASP), including IL-1ß, IL-6, and MMP-13, and it increased the expression of SIRT1. In addition, the protective effects of Que on cell senescence were partially reversed by miR-34a-5p overexpression and SIRT1 knockdown. In vivo, X-ray, and histological analyses indicated that Que alleviated IDD in a puncture-induced rat model. CONCLUSION: In summary, the present study provides evidence that Que reduces oxidative stress-induced senescence of NPMSCs via the miR-34a/SIRT1 signaling pathway, suggesting that Que may be a potential agent for the treatment of IDD.

Perioperative Hidden Blood Loss in Lumbar Disk Herniation Patients With Percutaneous Endoscopic Transforaminal Discectomy and Influencing Factors.

STUDY DESIGN: This was a retrospective study. OBJECTIVES: This study aimed to evaluate hidden blood loss (HBL) and its influencing factors in lumbar disk herniation (LDH) patients treated with percutaneous endoscopic transforaminal discectomy (PETD). SUMMARY OF BACKGROUND DATA: PETD is a minimally invasive spine surgery and is widely used to treat LDH. It is generally believed that there is less bleeding during PETD. However, HBL during the perioperative period is always ignored. MATERIALS AND METHODS: From January 2018 to March 2021, 74 LDH patients treated with PETD was selected. The patient's sex, age, height, weight, previous medical history (hypertension and diabetes) and other basic information were recorded. The preoperative fibrinogen (FIB) level, activated partial thromboplastin time and prothrombin time were recoded. The hemoglobin, hematocrit, and platelet immediately after admission and the next day postoperative were recorded. The surgical time, intraoperative blood loss, intervertebral disk degeneration grade and soft tissue thickness of the PETD approach were recorded. The total blood loss was calculated according to the Gross formula, and then HBL was calculated based on total blood loss and visible blood loss (VBL). The influencing factors were analyzed by single factor correlation analysis and multivariate linear regression analysis. RESULTS: Among the 74 patients, there were 34 males (20-68 y old) and 40 females (26-75 y old). The mean amount of VBL was (85.04±26.53) mL and HBL was (341.04±191.15) mL. There were statistically significant differences between HBL and VBL (P=0.000). Multiple linear regression analysis showed that sex (P=0.000), disk degeneration grade (P=0.000), preoperative FIB level (P=0.022) and preoperative platelet (P=0.026) were independent risk factors that contributed to HBL, but age (P=0.870), BMI (P=0.480), hypertension (P=0.867), diabetes (P=0.284), soft tissue thickness (P=0.701), preoperative prothrombin time (P=0.248) and preoperative activated partial thromboplastin time (P=0.521) were not. CONCLUSIONS: There was a large amount of HBL during the perioperative period of PETD in patients with LDH. Sex, disk degeneration grade, preoperative FIB level and preoperative platelet are the independent risk factors of HBL in the perioperative period of PETD. More attention should be paid to the patients with risk factors to ensure perioperative safety.

1,25(OH)2D3 Mitigates Oxidative Stress-Induced Damage to Nucleus Pulposus-Derived Mesenchymal Stem Cells through PI3K/Akt Pathway.

Intervertebral disc degeneration (IVDD) is one of the main causes of low back pain. The local environment of the degenerated intervertebral disc (IVD) increases oxidative stress and apoptosis of endogenous nucleus pulposus-derived mesenchymal stem cells (NPMSCs) and weakens its ability of endogenous repair ability in degenerated IVDs. A suitable concentration of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been certified to reduce oxidative stress and cell apoptosis. The current study investigated the protective effect and potential mechanism of 1,25(OH)2D3 against oxidative stress-induced damage to NPMSCs. The present results showed that 1,25(OH)2D3 showed a significant protective effect on NPMSCs at a concentration of 10-10 M for 24 h. Protective effects of 1,25(OH)2D3 were also exhibited against H2O2-induced NPMSC senescence, mitochondrial dysfunction, and reduced mitochondrial membrane potential. The Annexin V/PI apoptosis detection assay, TUNEL assay, immunofluorescence, western blot, and real-time quantitative polymerase chain reaction assay showed that pretreatment with 1,25(OH)2D3 could alleviate H2O2-induced NPMSC apoptosis, including the apoptosis rate and the expression of proapoptotic-related (Caspase-3 and Bax) and antiapoptotic-related (Bcl-2) proteins. The intracellular expression of p-Akt increased after pretreatment with 1,25(OH)2D3. However, these protective effects of 1,25(OH)2D3 were significantly decreased after the PI3K/Akt pathway was inhibited by the LY294002 treatment. In vivo, X-ray, MRI, and histological analyses showed that 1,25(OH)2D3 treatment relieved the degree of IVDD in Sprague-Dawley rat disc puncture models. In summary, 1,25(OH)2D3 efficiently attenuated oxidative stress-induced NPMSC apoptosis and mitochondrial dysfunction via PI3K/Akt pathway and is a promising candidate treatment for the repair of IVDD.

Urolithin a alleviates oxidative stress-induced senescence in nucleus pulposus-derived mesenchymal stem cells through SIRT1/PGC-1α pathway.

BACKGROUND: In degenerative intervertebral disc (IVD), an unfavorable IVD environment leads to increased senescence of nucleus pulposus (NP)-derived mesenchymal stem cells (NPMSCs) and the inability to complete the differentiation from NPMSCs to NP cells, leading to further aggravation of IVD degeneration (IDD). Urolithin A (UA) has been proven to have obvious effects in delaying cell senescence and resisting oxidative stress. AIM: To explore whether UA can alleviate NPMSCs senescence and to elucidate the underlying mechanism. METHODS: In vitro, we harvested NPMSCs from rat tails, and divided NPMSCs into four groups: the control group, H2O2 group, H2O2 + UA group, and H2O2 + UA + SR-18292 group. Senescence-associated ß-Galactosidase (SA-ß-Gal) activity, cell cycle, cell proliferation ability, and the expression of senescence-related and silent information regulator of transcription 1/PPAR gamma coactivator-1α (SIRT1/ PGC-1α) pathway-related proteins and mRNA were used to evaluate the protective effects of UA. In vivo, an animal model of IDD was constructed, and X-rays, magnetic resonance imaging, and histological analysis were used to assess whether UA could alleviate IDD in vivo. RESULTS: We found that H2O2 can cause NPMSCs senescence changes, such as cell cycle arrest, reduced cell proliferation ability, increased SA-ß-Gal activity, and increased expression of senescence-related proteins and mRNA. After UA pretreatment, the abovementioned senescence indicators were significantly alleviated. To further demonstrate the mechanism of UA, we evaluated the mitochondrial membrane potential and the SIRT1/PGC-1α pathway that regulates mitochondrial function. UA protected mitochondrial function and delayed NPMSCs senescence by activating the SIRT1/PGC-1α pathway. In vivo, we found that UA treatment alleviated an animal model of IDD by assessing the disc height index, Pfirrmann grade and the histological score. CONCLUSION: In summary, UA could activate the SIRT1/PGC-1α signaling pathway to protect mitochondrial function and alleviate cell senescence and IDD in vivo and vitro.