The influence of topical use of tranexamic acid in reducing blood loss on early operation for thoracolumbar burst fracture: a randomized double-blinded controlled study.

PURPOSE: To investigate the safety and efficacy of topical use of tranexamic acid (TXA) on early operation for thoracolumbar burst fracture (TBF). METHODS: Patients with acute TBF requiring early decompression were prospectively collected. The enrolled patients were randomly assigned to TXA and control group, in which wound surface was soaked with TXA or the same volume of normal saline for 5 min after wound incision, respectively. The total blood loss (TBL), intraoperative blood loss (IBL), postoperative blood loss (PBL), hemoglobin (HGB) levels on preoperatively (pre-op) and postoperatively, and amount of allogenic blood transfusion were recorded. Furthermore, the general information was also compared between groups. RESULTS: There were 39 and 37 patients enrolled in TXA and control group for final analysis. The demographics data showed no significant difference between groups (P > 0.05), but operation time and IBL were significantly decreased in TXA group (P < 0.05). Further analysis showed that HGB level was significantly higher in the TXA group at POD1, while the TBL and PBL were significantly less than those in the control group (P < 0.05), but similar to HBL (P > 0.05). The postoperative ambulation time, removal time of drainage tube, length of hospital stay, and blood transfusion rate were also significantly less in TXA group (P < 0.05). At the final follow-up, no neurological deteriorations and no TXA-related complications were observed in both groups. CONCLUSION: This RCT first demonstrated that topical TXA usage after wound incision could effectively reduce IBL without increasing risk of complications, beneficial to enhanced recovery after early operation for TBF.

HO-1 overexpression alleviates senescence by inducing autophagy via the mitochondrial route in human nucleus pulposus cells.

Intervertebral disc degeneration (IDD) is closely associated with aging. Our previous studies have confirmed that heme oxygenase-1 (HO-1) can inhibit nucleus pulposus (NP) cell apoptosis. However, whether or not HO-1 is involved in NP cell senescence and autophagy is unclear. Our results indicated that HO-1 expression was reduced in IDD tissues and replicative senescent NP cells. HO-1 overexpression using a lentiviral vector reduced the NP cell senescence level, protected mitochondrial function, and promoted NP cell autophagy through the mitochondrial pathway. Autophagy inhibitor 3-MA pretreatment reversed the anti-senescent and protective effects on the mitochondrial function of HO-1, which promoted the degradation of the extracellular matrix (ECM) in the intervertebral disc. In vivo, HO-1 overexpression inhibited IDD and enhanced autophagy. In summary, these results suggested that HO-1 overexpression alleviates NP cell senescence by inducing autophagy via the mitochondrial route.

Propionibacterium acnes induces intervertebral disc degeneration by promoting nucleus pulposus cell pyroptosis via NLRP3-dependent pathway.

Recent evidence suggests that Propionibacterium acnes (P. acnes) is a novel pathogenic factor promoting intervertebral disc degeneration (IVDD), however, whose mechanism remains unclear. A key component of inflammatory responses to P. acnes appears to be interleukin (IL)-1ß, which has been proved to be high expression in degenerative nucleus pulposus cells (NPCs). This study aimed to explore the inflammatory mechanism driving the host response to P. acnes infection in IVDD. Our data demonstrated that the number of nod-like receptor protein 3 (NLRP3)-positive cells was significantly increased in the P. acnes-infected nucleus pulposus (NP) tissue. Meanwhile, the up-regulated expressions of NLRP3, caspase-1, caspase-5, IL-1ß, IL-18, Gasdermin D (GSDMD) were observed in NPCs after co-culturing with P. acnes, which suggested NPCs pyroptosis activation induced by P. acnes. To further investigate the underlying mechanisms, NLRP3 inflammasome inhibitor MCC950 and thioredoxin binding protein (TXNIP)-siRNA were used. With the addition of MCC950 to NPCs co-cultured with P. acnes in vitro, the secretions of mature IL-1ß and IL-18 were reduced. Moreover, these MCC950-mediated effects were repeated by siRNA-transfected TXNIP knockdown. These results implied P. acnes activated inflammatory response by the TXNIP-NLRP3 pathway. To further reveal the anti-degeneration role of MCC950 in vivo, MCC950 was injected into the rabbit IVDD models infected by P. acnes. The MRI and histological detection provided more solid evidence that MCC950 treatment effectively retarded the degenerative process of the intervertebral discs in vivo. In summary, these results suggest that P. acnes-induced NPCs pyroptosis activation via the NLRP3-dependent pathway is likely responsible for the inflammatory pathology of IVDD. MCC950 can alleviate inflammatory injury and NPCs pyroptosis under P. acnes infection and may delay the progression of disc degeneration, which provides a new direction for the treatment of IVDD.

Leukemia inhibitory factor promotes extracellular matrix synthesis in degenerative nucleus pulposus cells via MAPK-ERK1/2 signaling pathway.

Extracellular matrix (ECM) anabolism and catabolism imbalance is key feature of chondrocyte and intervertebral disc nucleus pulposus (NP) cell degeneration. The role of LIF as a multifunctional cytokine in the ECM metabolism of chondrocytes is controversial, but no relevant research in the ECM metabolism of NP cells. This study aimed to explore the biofunction and related mechanisms of LIF in the degenerative NP cells. We obtained an increase in the expression of LIF in the human degenerated NP specimens. The addition of recombinant human leukemia inhibitory factor (rhLIF) to the degenerated NP cells cultured in vitro was found to stimulate the synthesis of ECM, and rhLIF could activate the ERK1/2 signaling pathway. However, coculture with PD98059, a signal inhibitor of ERK1/2, blocked the effect of rhLIF on the synthesis of ECM. To furtherly clarify the role of LIF, we carried out animal experiments and found that rhLIF treatment could successfully delay the degree of degeneration of the intervertebral disc in a rabbit model; but with the addition of PD98059, the function of rhLIF for degeneration protection disappeared. In summary, this study demonstrates that LIF plays a role in promoting ECM synthesis in the degenerated NP cells as a protective role in intervertebral disc degeneration (IDD), which is related to the activation of ERK1/2 signaling pathway.

Noninvasive, targeted gene therapy for acute spinal cord injury using LIFU-mediated BDNF-loaded cationic nanobubble destruction.

Various gene delivery systems have been widely studied for the acute spinal cord injury (SCI) treatment. In the present study, a novel type of brain-derived neurotrophic factor (BDNF)-loaded cationic nanobubbles (CNBs) conjugated with MAP-2 antibody (mAbMAP-2/BDNF/CNBs) was prepared to provide low-intensity focused ultrasound (LIFU)-targeted gene therapy. In vitro experiments, the ultrasound-targeted tranfection to BDNF overexpressioin in neurons and efficiently inhibition neuronal apoptosis have been demonstrated, and the elaborately designed mAbMAP-2/BDNF/CNBs can specifically target to the neurons. Furthermore, in a acute SCI rat model, LIFU-mediated mAbMAP-2/BDNF/CNBs transfection significantly increased BDNF expression, attenuated histological injury, decreased neurons loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in SCI rats. LIFU-mediated mAbMAP-2/BDNF/CNBs destruction significantly increase transfection efficiency of BDNF gene both in vitro and in vivo, and has a significant neuroprotective effect on the injured spinal cord. Therefore, the combination of LIFU irradiation and gene therapy through mAbMAP-2/BDNF/CNBs can be considered as a novel non-invasive and targeted treatment for gene therapy of SCI.

PINK1 protects against oxidative stress induced senescence of human nucleus pulposus cells via regulating mitophagy.

Intervertebral disc degeneration (IDD) is closely related with aging, whereas mitochondrial dysfunction is a common feature of aging in which results cell senescence. Phosphatase and tensin homolog (PTEN)-induced putative kinase protein 1 (PINK1) is a mitochondrial-targeted serine/threonine kinase, which plays a protective role against mitochondrial dysfunction with mitochondrial quality control by activating PINK1/Parkin mediated mitophagy. This study aimed to investigate the protective role of PINK1 against mitochondrial dysfunction and human nucleus pulposus cell (NPC) senescence. We found that mitochondrial dysfunction and NPC senescence could be induced under sublethal oxidative stress by 150 µM H2O2. Moreover, down-regulation of PINK1 tended to aggravate NPC senescence under oxidative stress. Therefore, mitophagy was evaluated in NPCs to further reveal the underlying mechanism. Results showed that sublethal oxidative stress induced mitochondria dysfunction and mitophagy in NPCs. Furthermore, depletion of PINK1 utilizing short hairpin RNA targeting PINK1 (PINK1-shRNA) impaired mitophagy, and exasperated NPC senescence under oxidative stress. In summary, these results suggested that PINK1 played as a protective role in clearance of damaged mitochondrial and alleviating cell senescence under oxidative stress, whose mechanism is associated with regulating mitophagy. These findings may provide a better understanding in pathomechanism of IDD and potential therapeutic approaches for IDD treatment.

Duhuo Jisheng Decoction inhibits SDF-1-induced inflammation and matrix degradation in human degenerative nucleus pulposus cells in vitro through the CXCR4/NF-κB pathway.

Lower back pain (LBP) is the most common disease in orthopedic clinics world-wide. A classic Fangji of traditional Chinese medicine, Duhuo Jisheng Decoction (DHJSD), has been proven clinically effective for LBP but its therapeutic mechanisms remain unclear. We hypothesized that DHJSD might relieve LBP through inhibiting the exaggerated proinflammatory cytokines and extracellular matrix (ECM) degradation. Thus, we studied the effects of DHJSD on stromal cell-derived factor-1 (SDF-1)-induced inflammation and ECM degradation in human nucleus pulposus cells (hNPCs). The primary hNPCs were isolated from either degenerated human intervertebral disc (HID) of LBP patients or normal HID of lumbar vertebral fracture patients, and cultured in vitro. The cells were treated with SDF-1 (10 ng/mL) and subsequently with different concentrations (100-500 µg/mL) of DHJSD for 24 h, respectively. We found that application of DHJSD significantly antagonized the SDF-1-induced production of proinflammatory cytokines and reduction of aggrecan and type II collagen in the hNPCs. DHJSD also markedly reduced the SDF-1-induced increase of CXCR4 and p-p65 and inhibited the nuclear translocation of p65 in the hNPCs. DHJSD, CXCR4-siRNA, and NF-κB inhibitor (BAY11-7082) caused the same inhibition of exaggerated proinflammatory cytokines in the SDF-1-treated hNPCs. These results provided compelling evidence that DHJSD may inhibit the generation of proinflammatory mediators and ECM degradation of HID through an orchestrated targeting at multiple molecules in the SDF-1/CXCR4/NF-κB pathway, thus offered novel mechanistic insights into the clinical effectiveness of DHJSD on LBP.

Calculation and Identification of the Aerodynamic Parameters for Small-Scaled Fixed-Wing UAVs.

The establishment of the Aircraft Dynamic Model(ADM) constitutes the prerequisite for the design of the navigation and control system, but the aerodynamic parameters in the model could not be readily obtained especially for small-scaled fixed-wing UAVs. In this paper, the procedure of computing the aerodynamic parameters is developed. All the longitudinal and lateral aerodynamic derivatives are firstly calculated through semi-empirical method based on the aerodynamics, rather than the wind tunnel tests or fluid dynamics software analysis. Secondly, the residuals of each derivative are proposed to be identified or estimated further via Extended Kalman Filter(EKF), with the observations of the attitude and velocity from the airborne integrated navigation system. Meanwhile, the observability of the targeted parameters is analyzed and strengthened through multiple maneuvers. Based on a small-scaled fixed-wing aircraft driven by propeller, the airborne sensors are chosen and the model of the actuators are constructed. Then, real flight tests are implemented to verify the calculation and identification process. Test results tell the rationality of the semi-empirical method and show the improvement of accuracy of ADM after the compensation of the parameters.

Resveratrol protects against mitochondrial dysfunction through autophagy activation in human nucleus pulposus cells.

Intervertebral disc degeneration (IVDD) is closely related with aging, whereas mitochondrial damage is a common feature of aging that results in cell apoptosis. Resveratrol (RES) is a natural antioxidant that protects against mitochondrial dysfunction in various cells. This study aimed to investigate the protective role of RES against mitochondrial dysfunction and human nucleus pulposus cell (NPC) apoptosis. We found that mitochondrial dysfunction and NPC apoptosis could be induced under oxidative stress by 100 µmol/l of H2O2. However, RES tended to attenuate the H2O2-mediated cytotoxicity. Therefore, autophagic state was evaluated in NPCs to further reveal the underlying mechanism. Results showed that RES reversed the impaired autophagy induced by H2O2, and this increased autophagic flux was confirmed by the addition of bafilomycin A1. Moreover, pretreatment with 3-methyladenine showed that the potential mechanism of RES to prevent deteriorating mitochondrial function and cell apoptosis was related to autophagy activation. Furthermore, MRI and histological detection were employed to provide more solid evidence that RES injection in an IVDD rabbit model effectively retards the degenerative process of the intervertebral discs in vivo. In summary, these results suggested that RES could alleviate mitochondrial dysfunction and cell apoptosis under oxidative stress and may delay the progression of disc degeneration, whose mechanism is associated with an advantageous role of autophagy induced by RES.

Microsurgery or open cervical foraminotomy for cervical radiculopathy? A systematic review.

OBJECTIVE: The purpose of this article was to systematically review the clinical outcomes of microendoscopic foraminotomy compared with the traditional open cervical foraminotomy. METHODS: A literature search of two databases was performed to identify investigations performed in the treatment of cervical foraminotomy with microsurgery or an open approach. Data including blood loss, surgical time, hospital stay, complications, clinical success rate, reduction of arm and neck pain, improvement of neurological function, and repeated surgery rate were summarized, calculated and compared. Results of clinical success were performed by calculattng effect indicators and standard errors based on a single rate to assess heterogeneity in the two groups. RESULTS: The initial literature search resulted in 713 articles, of which, 26 were determined as relevant on abstract review. An open foraminotomy approach was performed in 16 and a microsurgery approach in ten studies. The open group demonstrated minimal to moderate heterogeneity, with I (2) value of 27 %; and microsurgery group demonstrated minimal heterogeneity, with I (2) value of 1 %. Aggregated data found that patients treated by microsurgery foraminotomy have lower blood loss by 100.1 ml (open: 149.5 ml, microsurgery: 49.4 ml, n = 1257), shorter surgical time by 24.9 minutes (open 88.7 minutes, microsurgery 63.8 minutes, n = 1423),and shorter hospital stay by 3.0 days (open 4.1 days, microsurgery 1.1 days, n = 1350), compared with patients treated by open cervical foraminotomy. The pooled clinical success rate was 89.7 % [confidence interval (CI) 87.7-91.6) in the open group versus 92.5 % (CI 89.9-95.1) in the microsurgery group, with no statistical difference (p = 0.095). Overall complication rates were not statistically significant between groups (p = 0.757). The incidence of dural tears was 1.07 %( 12/1121) in patients undergoing microsurgery versus 0.27 % (2/745) for open surgery (p = 0.091). The incidence of infection was 0.54 % (6/1121) in patients undergoing microsurgery versus 0.40 % (3/745) for open surgery (p = 0.949). The incidence of root injury was 0.80 % (9/1121) in patients undergoing microsurgery versus 1.48 % (11/745) for open surgery (p = 0.166). Revision surgery occurred in 2.32 % (27/1163) in the microsurgery group versus 3.35 % (28/835) for traditional surgery, with no statistical difference (p = 0.164). Pooled reduction in visual analogue scale for the arm (VASA) was 75.0 % (CI 66.0-84.0) in the open group and 87.1 % (CI:76.7, 97.5) in the microsurgery group, with no statistical difference (p = 0.065). Pooled reduction in VAS of the neck (VASN) was 66.2 % (CI:52.2, 80.2) in the open group and 68.1 % (CI:36.4, 99.8) in the microsurgery group, with no statistical difference(p = 0.894). Pooled improvement in neurological function was 55.3 % (CI:18.6, 91.9) in the open group and 64.9 % (CI:34.6, 95.2) in the microsurgery group, with no statistical difference (p = 0.576). CONCLUSIONS: Although advantages of cervical microsurgery are less blood loss and shorter surgical time and hospital stay over the standard open technique, there is no significant difference in clinical success rate, complication rate, reduction of arm and neck pain and improvement of neurological function between microsurgery and open cervical foraminotomy.

Life's Essential 8 and osteoporosis in adults aged 50 years or older: data from the National Health and Nutrition Examination Survey.

In this cross-sectional study, we examined the association between Life's Essential 8 (LE8) and bone mineral density (BMD) as well as osteoporosis risk among adults aged 50 and over. The findings of this study revealed that higher LE8 scores were associated with higher BMD and reduced osteoporosis risk. PURPOSE: The objective of the present study was to evaluate the association between Life's Essential 8 (LE8) and bone mineral density (BMD), as well as osteoporosis risk, in adults aged 50 years or over. METHODS: This cross-sectional study recruited individuals who were 50 years old or older from the National Health and Nutrition Examination Survey. LE8 scores were evaluated and calculated according to the scoring algorithm based on the American Heart Association recommendations, which were further categorized into health behaviors (LE8-HB) and health factors (LE8-HF) scores. Furthermore, the present study utilized multivariate linear regression models to examine the correlations between BMD and LE8 scores. In addition, ordinal logistic regression models were employed to determine the associations between the risk of osteoporosis (normal BMD, osteopenia, and osteoporosis) and LE8 scores. RESULTS: The final analysis included a total of 2910 participants, whose mean age was 64.49 ± 9.28 years. LE8 and LE8-HF scores exhibited a negative association with BMD and a positive association with osteoporosis risk in unadjusted models. Nevertheless, after adjustment for covariates, LE8 and LE8-HB scores exhibited a positive association with BMD and a negative association with osteoporosis risk, regardless of age, sex, or menopausal status. CONCLUSIONS: Scoring systems based on multiple lifestyle and behavior factors, similar to LE8, have the potential to become a novel option and be used for osteoporosis risk assessment.

Ultrasound Nanobubble Coupling Agent for Effective Noninvasive Deep-Layer Drug Delivery.

Conventional coupling agents (such as polyvinylpyrrolidone, methylcellulose, and polyurethane) are unable to efficiently transport drugs through the skin's dual barriers (the epidermal cuticle barrier and the basement membrane barrier between the epidermis and dermis) when exposed to ultrasound, hindering deep and noninvasive transdermal drug delivery. In this study, nanobubbles prepared by the double emulsification method and aminated hyaluronic acid are crosslinked with aldehyde-based hyaluronic acid by dynamic covalent bonding through the Schiff base reaction to produce an innovative ultrasound-nanobubble coupling agent. By amplifying the cavitation effect of ultrasound, drugs can be efficiently transferred through the double barrier of the skin and delivered to deep layers. In an in vitro model of isolated porcine skin, this agent achieves an effective penetration depth of 728 µm with the parameters of ultrasound set at 2 W, 650 kHz, and 50% duty cycle for 20 min. Consequently, drugs can be efficiently delivered to deeper layers noninvasively. In summary, this ultrasound nanobubble coupling agent efficiently achieves deep-layer drug delivery by amplifying the ultrasonic cavitation effect and penetrating the double barriers, heralding a new era for noninvasive drug delivery platforms and disease treatment.

The effect of perioperative sequential application of multiple doses of tranexamic acid on postoperative blood loss after PLIF: a prospective randomized controlled trial.

BACKGROUND: Tranexamic acid (TXA) has been utilized in spinal surgery to effectively reduce intraoperative blood loss (IBL) and allogeneic blood transfusion rates. However, the traditional TXA regimen might last the entire duration of hyperfibrinolysis caused by surgical trauma, resulting in its limited ability to reduce postoperative blood loss (PBL). Therefore, the aim of this study was to investigate the effectiveness of perioperative sequential administration of multiple doses of TXA in reducing PBL in patients who underwent posterior lumbar interbody fusion (PLIF). METHODS: From October 2022 to June 2023, 231 patients who were diagnosed with lumbar degenerative disease and scheduled to undergo PLIF were prospectively enrolled in the present study. The patients were randomly divided into three groups. Moreover, all patients received an intravenous injection of TXA at a dose of 15 mg/kg 15 min before the surgical skin incision. Patients in Group A received a placebo of normal saline after surgery, while patients in Group B received three additional intravenous injections of TXA at a dose of 15 mg/kg every 24 h. Patients in Group C received three additional intravenous injections of TXA at a dose of 15 mg/kg every 5 h. The primary outcome measure was PBL. In addition, this study assessed total blood loss (TBL), IBL, routine blood parameters, liver and kidney function, coagulation parameters, fibrinolysis indexes, inflammatory indicators, drainage tube removal time (DRT), length of hospital stay (LOS), blood transfusion rate, and incidence of complications for all subjects. RESULTS: The PBL, TBL, DRT, and LOS of Group B and Group C were significantly lower than those of Group A ( P <0.05). The level of D-dimer (D-D) in Group C was significantly lower than that in Group A on the first day after the operation ( P =0.002), and that in Group B was significantly lower than that in Group A on the third day after the operation ( P =0.003). The interleukin-6 levels between the three groups from 1 to 5 days after the operation were in the order of Group A > Group B > Group C. No serious complications were observed in any patient. The results of multiple stepwise linear regression analysis revealed that PBL was positively correlated with incision length, IBL, smoking history, history of hypertension, preoperative fibrinogen degradation product level, and blood transfusion. It was negatively correlated with preoperative levels of fibrinogen, red blood cells, blood urea nitrogen, and age. Compared to female patients, male patients had an increased risk of PBL. Finally, the incidence of PBL was predicted. CONCLUSIONS: Sequential application of multiple doses of TXA during the perioperative period could safely and effectively reduce PBL and TBL, shorten DRT and LOS, reduce postoperative D-D generation, and reduce the postoperative inflammatory response. In addition, this study provided a novel prediction model for PBL in patients undergoing PLIF.

[Purification and biological osteoinductive activity analysis of recombinant human bone morphogenetic protein 9 by eukaryotic expression].

The present paper is aimed to explore the biological osteoinductive activity of recombinant human bone morphogenetic protein 9 (rhBMP-9) by various biological technologies. In this study, we firstly obtained hBMP-9 cDNA by PCR and inserted it into vector pcDNA4/His Max to reconstruct hBMP-9 eukaryotic expression vector pcDNA4/His Max-BMP-9. Recombinant Chinese hamster ovary (rCHO) cell line expressing high-level rhBMP-9 was reconstructed by co-transfecting the expression vectors pcDNA4/His* Max-hBMP-9 and plasmid pSV2-dhfr into dihydrofolate reductase (dhfr)-deficient CHO cells and the subsequent gene amplification by the methotrexate. We finally obtained a monoclonal cell line expressing the highest level protein. We purified the medium after culturing the highest-producing monoclonal by Ni-NTA His-Bind Resin columns and concentrated to by a Centricon 50 at 4 degrees C and stored at 70 degrees C until it was used. Western blot and SDS-PAGE analyses showed a specific band of about 32kD in pro-region lane and a specific band of about 50kD in pro-region complex lane. Biological activities of rhBMP-9 were tested by colorimetric determination and histochemical staining of Alkaline Phosphatase (ALP) Activity, osteocalcin and oesteopontin for C3H10 T1/2 cells, which were stimulated culture by different concentration (20, 50, 100 microg/mL) of rhBMP-9. The results showed that the rhBMP-9 could induce osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro, and were proportional to the amount. This study can provide experimental data for further tests in vivo and clinical applications.

A systematic review and meta-analysis of cemented and uncemented bipolar hemiarthroplasty for the treatment of femoral neck fractures in elderly patients over 60 years old.

Background: Currently, whether bone cement can be applied in bipolar hemiarthroplasty to treat femoral neck fractures (FNFs) in elderly patients is controversial. The aim of this systematic review and meta-analysis was to compare the effectiveness and safety of cemented bipolar hemiarthroplasty (CBH) versus uncemented bipolar hemiarthroplasty (UCBH) in the treatment of FNFs among elderly patients over 60 years old. Materials and methods: The Pubmed, Web of science, Cochrane Library and EMBASE databases were searched comprehensively for relevant articles from their inception to May 2022. Studies about comparing outcomes between CBH and UCBH for FNFs in elderly patients aged more than 60 years were included. Outcomes including operation time, intra-operative blood loss, length of hospital stay, wound infections, residual pain, revisions, re-operations, complications related to prosthesis, general complications, and mortality. The Review Manager 5.3 software provided by the Cochrane Collaboration Network was used to perform the meta-analysis of comparable data. Results: A total of 6 randomized controlled trials (RCTs) and 9 observational studies were included in this analysis, with 33,118 patients (33,127 hips). Results of the meta-analysis indicated that the operation time [WMD = 13.01 min, 95% CI (10.79, 15.23)], intra-operative blood loss [WMD = 80.57 ml, 95% CI (61.14, 99.99)], incidence of heterotrophic ossification [OR = 2.07, 95% CI (1,14, 3.78)], were increased in the CBH group but the incidence of intra-operative fractures [OR = 0.24, 95% CI (0.07, 0.86)], periprosthetic fractures [OR = 0.24, 95% CI (0.18, 0.31)], aseptic loosening of prosthesis [OR = 0.20, 95% CI (0.09, 0.44)], wound infections [OR = 0.80, 95% CI (0.68, 0.95)] and re-operation rates [OR = 0.61, 95% CI (0.54, 0.68)] were lower in the CBH group by comparison with the UCHB group. However, there were no significant differences in residual pain, length of hospital stay, prosthetic dislocation, prosthetic subsidence (> 5 mm), acetabulum erosion, revisions, pulmonary infections, pulmonary embolisms, urinary tract infections, deep venous thromboses, decubitus, cardiovascular accidents (arrhythmia/myocardial infarction), and respiratory failure between the two groups. In terms of mortality, perioperative mortality (within 72 h) [OR = 2.39, 95% CI (1.71, 3.32)] and 1-week mortality postoperatively [OR = 1.22, 95% CI (1.05, 1.41)] in CBH group were higher than those in UCBH group, but there were no significant differences in mortality at 1 month, 3 months, 1 year, and 2 years postoperatively between CBH group and UCBH group. Conclusion: This meta-analysis found that elderly patients over 60 years old with FNFs who underwent CBH had longer operation time, higher incidence of heterotrophic ossification, intra-operative blood loss, and mortality within 72 h of operation and at 1-week postoperatively, but lower incidence of periprosthetic fractures, aseptic loosening of prosthesis, intra-operative fractures, wound infections and re-operations. Other outcomes were not significantly different between the two groups. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021274253.

Ultrasonic-controlled "explosive" hydrogels to precisely regulate spatiotemporal osteoimmune disturbance.

Spatiotemporal Immune disorder is a key factor leading to the failure of bone tissue healing. It is of vital importance to accurately suppress excessive peak immune response within 24-48 h of the injury and so regulate the spatiotemporal osteoimmune disturbance of bones. In this study, Ultrasound Controlled "Explosive" (UCE) hydrogels were prepared from gelatin-hyaluronic acid methacrylate hydrogels loaded with resveratrol nanobubbles produced by double emulsification through a condensation reaction. Such materials innovatively enable ultrasound-controlled RES release for precise regulation of spatiotemporal osteoimmune disorders. Under an ultrasonic power level of 1.5 W/cm2, the rate of effectively released RES through the blast of UCE hydrogels reached 38.14 %. And compared with the control group, the in vivo inhibition of inflammation and osteogenesis effects of UCE hydrogels were more effective, respectively. As suggested by the results, the excessive local inflammatory response was inhibited by the release of resveratrol, the temporospatial disorder of bone immune was precisely regulated, and as a result, the process of bone repair was accelerated. Altogether, this study confirms that the newly created UCE Hydrogels effectively promote bone repair by intervening peak inflammation during the early phase of fracture healing.

The effect of sequential perioperative intravenous tranexamic acid in reducing postoperative blood loss and hidden blood loss after posterior lumbar interbody fusion: a randomized controlled trial.

Background: Tranexamic acid (TXA) has previously been shown to be effective in reducing intraoperative blood loss (IBL) and transfusion requirements in spine surgery. A conventional TXA regimen is a simple preoperative or intraoperative administration. However, the hyperfibrinolysis caused by surgical trauma lasts at least 24 h, and a single dose of TXA cannot cover the whole process of hyperfibrinolysis. Moreover, its ability to control postoperative blood loss (PBL) may be insufficient. Therefore, this study aimed to explore the effects and safety of sequential perioperative intravenous TXA for reducing bleeding after posterior lumbar interbody fusion (PLIF). Methods: Patients requiring PLIF were randomly divided into two groups. All patients were intravenously injected with 1 g of TXA 15 min before skin resection. Every day after the surgery, 200 ml saline was intravenously injected for 1-3 days in Group A, while Group B received 1 g of TXA instead of saline. The total blood loss (TBL), IBL, PBL, HCT, Hb, blood transfusion volume, inflammation-related indicators, and complications were recorded. Results: TBL, PBL, and hidden blood loss (HBL) in Group B were significantly lower than those in Group A (P < 0.05). The maximum decreases in HCT and Hb in Group B were also significantly lower than those in Group A (P < 0.05), and the drainage removal time (DRT) was sooner in Group B than in Group A (P = 0.003). On the 3rd and 5th days after surgery, the level of CRP in Group B was significantly lower than that in Group A (P < 0.05). Similarly, IL-6 levels were significantly lower in Group B for the first 5 days postoperatively (P < 0.001). Sex, operation time, level of decompression, length of incision, and change in HCT were significant predictors of both TBL and HBL. TBL was also significantly associated with BMI and preoperative fibrinogen, while postoperative TXA was a significant predictor of HBL only. Conclusion: Intravenous injection of 1 g of TXA 15 min before skin resection combined with continuous intravenous injection of 1 g of TXA 1 to 3 days after PLIF can reduce postoperative bleeding and shorten the time to drainage tube removal. In addition, it can also inhibit the postoperative inflammatory response. Clinical trial registration: ChiCTR2200056210.

Clinical application of a modified predeposit autologous red blood cell apheresis in multistage spinal fusion: a single-center retrospective study.

Purpose: This study aimed to evaluate the efficacy and safety of predeposit autologous RBC apheresis (PARA) in patients undergoing multilevel spinal fusion surgery. Methods: A total of 112 patients from January 2020 to June 2022 were divided into two groups according to PARA: the PARA group (n = 51) and the control group (n = 61). The baseline characteristics of the patients, outcomes, transfusion cost, hospitalization cost, length of stay, complications, and changes in hemoglobin and hematocrit levels between the two groups were compared. Results: The baseline characteristics were similar in both groups. No significant differences were found in functional outcomes, including VAS score (p = 0.159), ODI score (p = 0.214), JOA score (p = 0.752), and SF-36 score (p = 0.188) between the PARA and control groups. The amount and rate of intraoperative and perioperative allogeneic RBC transfusion were significantly higher in the control group than in the PARA group (p < 0.001). The postoperative (9.04 ± 3.21 vs. 11.05 ± 3.84, p = 0.004) and total length of stay (15.78 ± 3.79 vs. 17.36 ± 4.08, p = 0.038) in the PARA group were significantly lower than those in the control group, respectively. Despite no difference in hospitalization cost (p = 0.737), the total blood transfusion cost in the PARA group was significantly lower, compared with the control group (p < 0.001). For safety evaluation, there were no significant differences in Hb and Hct levels between the two groups at admission, on postoperative day 1, and postoperative day 3, respectively (p > 0.05). Moreover, the number of postoperative infections in the PARA group was significantly lower than that in the control group (p = 0.038). Conclusion: PARA was a novel, safe, and highly efficient technique for mass autologous blood preparation in a quite short preparation time. This method could significantly reduce the amount of allogeneic blood transfusion and length of stay, which could provide a theoretical basis for following clinical practice about the technique.

Efficacy and Safety of Erector Spinae Plane Block for Perioperative Pain Management in Lumbar Spinal Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Since the application of ultrasound-guided erector spinae plane block (ESPB) in 2016, the approach has been gradually applied to perioperative analgesia in various surgeries. In recent years, more and more studies have focused on the effect of ESPB in perioperative analgesia of lumbar spinal surgery, but its clinical effect remains controversial. Objective: This systematic review and meta-analysis was designed to explore the efficacy and safety of ESPB used for perioperative pain management in lumbar spinal surgery. Methods: The Pubmed, Web of Science, Cochrane Library, and EMBASE databases were comprehensively searched for relevant articles from inception to March 2022. Randomized controlled trials (RCTs) comparing ESPB with placebo or without ESPB in lumbar spinal surgery were included. The Review Manager 5.3 software was employed for this meta-analysis. Results: Nineteen RCTs with 1381 participants were included for final analysis. ESPB group exhibited lower intraoperative consumption of sufentanil and remifentanil, lower total opioid consumption within 24 h and 48 h after surgery, lower incidence of rescue analgesia, longer time to first rescue analgesic and lower number of PCA button presses compared to the control group (P<0.05). Moreover, the ESPB group had significantly lower pain scores at rest and on movement within 48 h after surgery compared with the control group (P<0.05). In terms of opioid-related adverse reactions, ESPB reduced the incidence of postoperative nausea, vomitting, somnolence and itching in comparison to the control group (P<0.05). ESPB-related serious complications were not reported in included studies. Conclusion: This meta-analysis demonstrated that ESPB used in lumbar spinal surgery was effective in relieving postoperative pain, decreasing the perioperative consumption of opioids, as well as decreasing the incidence of postoperative opioid-related adverse reactions.

Use of a Multifunctional Cocktail for Postoperative Bleeding and Pain Control in Spinal Fusion: A Randomized, Double-blind, Controlled Trial.

STUDY DESIGN: A prospective, randomized, double-blind controlled trial. OBJECTIVE: To explore the effect of multifunctional cocktail for bleeding and pain control after spinal fusion. SUMMARY OF BACKGROUND DATA: Managing postoperative bleeding and pain after spinal fusion remains a challenge. Topical application of tranexamic acid or anesthetic agents for bleeding or pain management just started recently, and the multifunctional cocktail for bleeding and pain control simultaneously after spinal fusion have never been published. METHODS: Ninety patients who underwent posterior spinal fusion were enrolled in this study. The multifunctional cocktail was injected into the incision before wound closure in the cocktail group. In the control group, an equal volume of normal saline was injected and a patient-controlled analgesic pump was used. Visual analogue scale score; opioid consumption; intraoperative, postoperative, hidden and total blood loss; volume of drainage, hematocrit levels of drainage; hemoglobin levels; and complications were compared between the two groups. RESULTS: There were no differences in the visual analogue scale within 48 hours after surgery between the two groups. However, the opioid dosages in the control group were higher than those in the cocktail group. The postoperative blood loss, total blood loss, and hidden blood loss were lower in the cocktail group than in the control group. The drainage volume showed no differences between the two groups; however, the hematocrit level of drainage at 24 hours after surgery was lower in the cocktail group than in the control group. The hemoglobin level was higher in the cocktail group than in the control group at postoperative day 3. Thirteen patients with unbearable nausea and vomiting in the control group, whereas no complications in the cocktail group. CONCLUSION: Topical application of a multifunctional cocktail that we designed provides an effective and safe method for reducing pain and bleeding after spinal fusion.