IL-1ra loaded chondroitin sulfate-functionalized microspheres for minimally invasive treatment of intervertebral disc degeneration.

Presently, the clinical treatment of intervertebral disc degeneration (IVDD) remains challenging, but the strategy of simultaneously overcoming the overactive inflammation and restoring the anabolic/catabolic balance of the extracellular matrix (ECM) in the nucleus pulposus (NP) has become an effective way to alleviate IVDD. IL-1ra, a natural antagonist against IL-1ß, can mitigate inflammation and promote regeneration in IVDD. Chondroitin sulfate (CS), an important component of the NP, can promote ECM synthesis and delay IVDD. Thus, these were chosen and integrated into functionalized microspheres to achieve their synergistic effects. First, CS-functionalized microspheres (GelMA-CS) with porous microstructure, good monodispersion, and about 200 µm diameter were efficiently and productively fabricated using microfluidic technology. After lyophilization, the microspheres with good local injection and tissue retention served as the loading platform for IL-1ra and achieved sustained release. In in vitro experiments, the IL-1ra-loaded microspheres exhibited good cytocompatibility and efficacy in inhibiting the inflammatory response of NP cells induced by lipopolysaccharide (LPS) and promoting the secretion of ECM. In in vivo experiments, the microspheres showed good histocompatibility, and local, minimally invasive injection of the IL-1ra-loaded microspheres could reduce inflammation, maintain the height of the intervertebral disc (IVD) and the water content of NP close to about 70 % in the sham group, and retain the integrated IVD structure. In summary, the GelMA-CS microspheres served as an effective loading platform for IL-1ra, eliminated inflammation through the controlled release of IL-1ra, and promoted ECM synthesis via CS to delay IVDD, thereby providing a promising intervention strategy for IVDD. STATEMENT OF SIGNIFICANCE: The strategy of simultaneously overcoming the overactive inflammation and restoring the anabolic/catabolic balance of the extracellular matrix (ECM) in nucleus pulposus (NP) has shown great potential prospects for alleviating intervertebral disc degeneration (IVDD). From the perspective of clinical translation, this study developed chondroitin sulfate functionalized microspheres to act as the effective delivery platform of IL-1ra, a natural antagonist of interleukin-1ß. The IL-1ra loading microspheres (GelMA-CS-IL-1ra) showed good biocompatibility, good injection with tissue retention, and synergistic effects of inhibiting the inflammatory response induced by lipopolysaccharide and promoting the secretion of ECM in NPCs. In vivo, they also showed the beneficial effect of reducing the inflammatory response, maintaining the height of the intervertebral disc and the water content of the NP, and preserving the integrity of the intervertebral disc structure after only one injection. All demonstrated that the GelMA-CS-IL-1ra microspheres would have great promise for the minimally invasive treatment of IVDD.

[Improved unilateral puncture PVP based on 3D printing technology for the treatment of osteoporotic vertebral compression fracture].

OBJECTIVE: To investigate the clinical effect of unilateral percutaneous vertebroplasty (PVP) combined with 3D printing technology for the treatment of thoracolumbar osteoporotic compression fracture. METHODS: A total of 77 patients with thoracolumbar osteoporotic compression fractures from October 2020 to April 2022 were included in the study, all of which were vertebral body compression fractures caused by trauma. According to different treatment methods, they were divided into experimental group and control group. Thirty-two patients used 3D printing technology to improve unilateral transpedicle puncture vertebroplasty in the experimental group, there were 5 males and 27 females, aged from 63 to 91 years old with an average of (77.59±8.75) years old. Forty-five patients were treated with traditional bilateral pedicle puncture vertebroplasty, including 7 males and 38 females, aged from 60 to 88 years old with an average of(74.89±7.37) years old. Operation time, intraoperative C-arm X-ray times, anesthetic dosage, bone cement injection amount, bone cement diffusion good and good rate, complications, vertebral height, kyphotic angle (Cobb angle), visual analogue scale(VAS), Oswestry disability index (ODI) and other indicators were recorded before and after surgery, and statistically analyzed. RESULTS: All patients were followed up for 6 to 23 months, with preoperative imaging studies, confirmed for thoracolumbar osteoporosis compression fractures, two groups of patients with postoperative complications, no special two groups of patients' age, gender, body mass index (BMI), time were injured, the injured vertebral distribution had no statistical difference(P>0.05), comparable data. Two groups of patients with bone cement injection, bone cement dispersion rate, preoperative and postoperative vertebral body height, protruding after spine angle(Cobb angle), VAS, ODI had no statistical difference(P>0.05). The operative time, intraoperative fluoroscopy times and anesthetic dosage were statistically different between the two groups(P<0.05). Compared with the traditional bilateral puncture group, the modified unilateral puncture group combined with 3D printing technology had shorter operation time, fewer intraoperative fluoroscopy times and less anesthetic dosage. The height of anterior vertebral edge, kyphosis angle (Cobb angle), VAS score and ODI of the affected vertebrae were statistically different between two groups at each time point after surgery(P<0.05). CONCLUSION: In the treatment of thoracolumbar osteoporotic compression fractures, 3D printing technology is used to improve unilateral puncture PVP, which is convenient and simple, less trauma, short operation time, fewer fluoroscopy times, satisfactory distribution of bone cement, vertebral height recovery and kyphotic Angle correction, and good functional improvement.

Cytomodulin-10 modified GelMA hydrogel with kartogenin for in-situ osteochondral regeneration.

The incidence of osteochondral defect is increasing year by year, but there is still no widely accepted method for repairing the defect. Hydrogels loaded with bioactive molecules have provided promising alternatives for in-situ osteochondral regeneration. Kartogenin (KGN) is an effective and steady small molecule with the function of cartilage regeneration and protection which can be further boosted by TGF-ß. However, the high cost, instability, and immunogenicity of TGF-ß would limit its combined effect with KGN in clinical application. In this study, a composite hydrogel CM-KGN@GelMA, which contained TGF-ß1 analog short peptide cytomodulin-10 (CM-10) and KGN, was fabricated. The results indicated that CM-10 modified on GelMA hydrogels exerted an equivalent role in enhancing chondrogenesis as TGF-ß1, and this effect was also boosted when combined with KGN. Moreover, it was revealed that CM-10 and KGN had a synergistic effect on promoting the chondrogenesis of BMSCs by up-regulating the expression of RUNX1 and SOX9 at both mRNA and protein levels in vitro. Finally, the composite hydrogel exhibited a satisfactory osteochondral defect repair effect in vivo, showing similar structures close to the native tissue. Taken together, this study has revealed that CM-10 may serve as an alternative for TGF-ß1 and can collaborate with KGN to accelerate chondrogenesis, which suggests that the fabricated CM-KGN@GelMA composite hydrogel can be acted as a potential scaffold for osteochondral defect regeneration. STATEMENT OF SIGNIFICANCE: Kartogenin and TGF-ß have shown great value in promoting osteochondral defect regeneration, and their combined application can enhance the effect and show great potential for clinical application. Herein, a functional CM-KGN@GelMA hydrogel was fabricated, which was composed of TGF-ß1 mimicking peptide CM-10 and KGN. CM-10 in hydrogel retained an activity like TGF-ß1 to facilitate BMSC chondrogenesis and exhibited boosting chondrogenesis by up-regulating RUNX1 and SOX9 when being co-applied with KGN. In vivo, the hydrogel promoted cartilage regeneration and subchondral bone reconstruction, showing similar structures as the native tissue, which might be vital in recovering the bio-function of cartilage. Thus, this study developed an effective scaffold and provided a promising way for osteochondral defect repair.

Transformation of arginine into zero-dimensional nanomaterial endows the material with antibacterial and osteoinductive activity.

Implant-associated infection is a major threat affecting the success of orthopedic surgeries. Although various materials scavenge bacteria by generating reactive oxygen species (ROS), the intrinsic inability of ROS to distinguish bacteria from cells notably limits the therapeutic effects. Here, we found that the arginine carbon dots (Arg-CDs) that were transformed from arginine exhibited supreme antibacterial and osteoinductive activity. We further designed the Schiff base bond between Arg-CDs and aldehyde hyaluronic acid/gelatin methacryloyl (HG) hydrogel to release Arg-CDs in response to the acidic bone injury microenvironment. The free Arg-CDs could selectively kill bacteria by generating excessive ROS. Furthermore, the Arg-CD-loaded HG composite hydrogel showed excellent osteoinductive activity through inducing the M2 polarization of macrophages by up-regulating interleukin-10 (Il10) expression. Together, our findings revealed that transformation of the arginine into zero-dimensional Arg-CDs could endow the material with exceptional antibacterial and osteoinductive activity, favoring the regeneration of infectious bone.

Correction: Preparation and characterizations of an injectable and biodegradable high-strength iron-bearing brushite cement for bone repair and vertebral augmentation applications.

Correction for 'Preparation and characterizations of an injectable and biodegradable high-strength iron-bearing brushite cement for bone repair and vertebral augmentation applications' by Luguang Ding et al., Biomater. Sci., 2023, 11, 96-107, https://doi.org/10.1039/D2BM01535H.

Early osteoimmunomodulation by mucin hydrogels augments the healing and revascularization of rat critical-size calvarial bone defects.

The design principle of osteogenic bone grafts has shifted from immunological inertness to limiting foreign body response to combined osteoimmunomodulatory activity to promote high-quality endogenous bone regeneration. Recently developed immunomodulatory mucin hydrogels have been shown to elicit very low complement activation and suppress macrophage release and activation after implantation in vivo. However, their immunoregulatory activity has not yet been studied in the context of tissue repair. Herein, we synthesized mucin-monetite composite materials and investigated their early osteoimmunomodulation using a critical-size rat bone defect model. We demonstrated that the composites can polarize macrophages towards the M2 phenotype at weeks 1 and 2. The early osteoimmunomodulation enhanced early osteogenesis and angiogenesis and ultimately promoted fracture healing and engraftment (revascularization of the host vasculature) at weeks 6 and 12. Overall, we demonstrated the applicability of mucin-based immunomodulatory biomaterials to enhance tissue repair in tissue engineering and regenerative medicine.

CircFOXK2 Promotes the Progression of Osteoarthritis by Regulating the miR-4640-5p/NOTCH2 Axis.

OBJECTIVE: Osteoarthritis (OA) is the most common age-related chronic and disabling joint disease, frequently causing pain and disability in the adult population. Given that there are no proven disease-modifying drugs for OA, it is urgent to gain a deeper understanding of OA pathogenesis. This study intended to uncover the circFOXK2 regulation in OA. METHODS: Firstly, in vitro OA cell model was constructed by treating murine chondrocytes with interleukin (IL)-1ß. Then, a series of functional assays were conducted to evaluate the effect of circFOXK2 on OA progression in murine chondrocytes. Bioinformatics analysis and mechanism investigations were performed to investigate the competitive endogenous RNA (ceRNA) network of circFOXK2 in OA. RESULTS: CircFOXK2 is overexpressed in IL-1ß-treated chondrocyte. We confirmed the cyclic structure and cytoplasmic distribution of circFOXK2. Functionally, circFOXK2 promotes chondrocyte apoptosis and extracellular matrix (ECM) degradation but inhibiting chondrocyte proliferation. Mechanically, circFOXK2 competitively binds to microRNA-4640-5p (miR-4640-5p) to enhance NOTCH2 expression in OA, affecting OA progression. Besides, circFOXK2 could motivate the Notch pathway to accelerate OA progression. CONCLUSION: CircFOXK2/miR-4640-5p/NOTCH2 axis stimulates the Notch pathway to promote the transcription of inflammatory cytokines (IL33, IL17F and IL6), consequently facilitating OA progression in murine chondrocytes.

Preparation and characterizations of an injectable and biodegradable high-strength iron-bearing brushite cement for bone repair and vertebral augmentation applications.

Brushite cements have good osteoconductive and resorbable properties, but the low mechanical strength and poor injectability limit their clinical applications in load-bearing conditions and minimally invasive surgery. In this study, an injectable brushite cement that contains monocalcium phosphate monohydrate (MCPM) and ß-tricalcium phosphate (ß-TCP) as its solid phase and ammonium ferric citrate (AFC) solution as the aqueous medium was designed to have high mechanical strength. The optimized formulation achieved a compressive strength of 62.8 ± 7.2 MPa, which is above the previously reported values of hand-mixing brushite cements. The incorporation of AFC prolonged the setting times and greatly enhanced the injectability and degradation properties of the cements. In vitro and in vivo experiments demonstrated that the brushite cements exhibited good biocompatibility and bone regeneration capacity. The novel brushite cement is promising for bone healing in load-bearing applications.

Individualized 3D printed navigation template-assisted atlantoaxial pedicle screws vs. free-hand screws for the treatment of upper cervical fractures.

Objective: This study aims to compare the efficacy and safety of freehand atlantoaxial pedicle screws against custom 3D printed navigation template screws in the treatment of upper cervical fractures. Methods: In our institution from 2010 to 2020, a retrospective cohort analysis of 23 patients with upper cervical fractures was done. These patients were separated into two groups: group A (N = 12), which received customized 3D printed navigation template-assisted screws with virtual reality techniques, and group B (N = 11), which received freehand screws assisted by intraoperative fluoroscopy. Every patient was monitored for more than 1 year. The two groups were contrasted in terms of screw implant accuracy, cervical spine Japanese Orthopaedic Association (JOA) score, American Spinal Injury Association (ASIA) score, visual analogue scale (VAS) score, surgical time, fluoroscopy times, and intraoperative blood loss. Results: A total of 88 atlantoaxial pedicle screws in all, 46 in group A and 42 in group B, were implanted. In group A, the screw insertion accuracy rate was 95.7%, compared to 80.0% in group B (P < 0.05). When compared to group B, group A had shorter surgery times, less blood loss, fewer fluoroscopies, a higher short-term JOA score, and overt pain reduction (P < 0.05). However, there was no discernible difference between the two groups' VAS scores, long-term JOA scores, or ASIA scores (sensory and motor), at the most recent follow-up. Conclusion: Individualized 3D printed guide leads to significant improvement in the screw safety, efficacy, and accuracy, which may be a promising strategy for the treatment of upper cervical fractures.

Non-gelated polymeric photonic crystal films.

A rapid curing method for the preparation of colloidal photonic crystal films is presented. Firstly, a colloidal crystal array template was prepared by self-assembly of nanospheres, and then a dilute polymer solution was poured into the gap of the template. Then the composite photonic film was obtained as the polymer solution was cured. Such films have good properties in mechanical strength, anti pH interference, rapid solvent response and are easy to preserve. The films show good linear response to ethanol aqueous solutions of different concentrations, and the response equilibrium takes less than 20 s. The films also show long-term stability and reusability, and further functionalization can make the films multi-sensitive.

Surgical treatment for upper cervical deformity with atlantoaxial joint dislocation using individualized 3D printing occipitocervical fusion instrument: A case report and literature review.

ABSTRACT: To introduce a novel technique of using individualized 3D printing occipitocervical fusion instrument (3D-OCF) for the treatment of upper cervical deformity with atlantoaxial joint dislocation.The surgery for deformity of the craniocervical junction area is a challenge in the field of spine. If the surgical deviation is too large to injure the spinal cord or vertebral artery, it will cause catastrophic damage to the patient. Therefore, it is controversial whether these patients should undergo surgical treatment. We provide a novel surgical approach for the challenging upper cervical surgery through 3D-OCF and a typical patient.We present a 54-year-old female patient, who suffered from dizziness and numbness in her limbs for 8 months. After the patient was admitted, we performed the three-dimensional CT scan, modeled using Mimics software 17.0, and designed customized occipitocervical fusion instrument. Besides, we repeatedly perform simulated surgery based on 3D-printed models before surgery.The operative time was 142 minutes and the intraoperative blood loss was 700 mL. X-ray showed reduction of atlantoaxial dislocation and accurate position of internal fixation. The patient's symptoms were significantly relieved: the sensation of dizziness and numbness of limbs was obviously relieved, and the sense of banding in chest, abdomen, and ankle was disappeared. At the last follow-up, imaging showed that 3D-OCF had bone-integration and Syringomyelia was disappeared. The patient's cervical JOA (Japanese Orthopaedic Association) score increased from 10 points to 17 points.Individualized 3D-OCF can improve the safety and accuracy of upper cervical surgery, reduce the operative time and the number of fluoroscopy. Our study provides a novel surgical approach for the challenging upper cervical surgery.

Quercetin reduces tendon adhesion in rat through suppression of oxidative stress.

BACKGROUND: Tendon adhesion is one of the most common clinical problems, which poses a considerable challenge to orthopedics doctors. Quercetin (QUE) as a popular drug at present, it has various biological functions, including anti-inflammatory, anti-ischemic, anti-peroxidation, and antioxidant. The purpose of this study was to investigate the effect of quercetin on tendon adhesion and whether quercetin can inhibit oxidative stress. METHOD: Thirty-six rats were randomly divided into three groups, including control group, low QUE (50 mg/kg/day) group, and high QUE (100 mg/kg/day) group. After 1 week, the levels of SOD, MDA and GPx were measured. The degree of tendon adhesion was assessed by macroscopic evaluation and histological evaluation. After 4 weeks. Besides, the pharmacological toxicity of quercetin to main organs were evaluated by histological analysis. RESULTS: The extent of superoxide dismutase (SOD) and glutathione peroxidase (GPx) of tendon tissue in high QUE group was significantly higher than those of low QUE group and control group. And the extent of malondialdehyde (MDA) of tendon tissue in high QUE group was significantly lower than that of low QUE group and control group. By macroscopic evaluation and histological analysis, the extent of tendon adhesion in high QUE group was lower than low QUE group and control group. However, there were no significant changes of the major organs through histological analysis. CONCLUSIONS: Quercetin may be a good and safe strategy in preventing tendon adhesion. But further clinical research is needed before its recommendation in the prevention and treatment of tendon adhesion.

Comparison of targeted percutaneous vertebroplasty and traditional percutaneous vertebroplasty for the treatment of osteoporotic vertebral compression fractures in the elderly.

OBJECTIVE: To investigate the clinical effect of precise puncture and low-dose bone cement in percutaneous vertebroplasty (PVP). METHODS: Sixty patients with osteoporotic vertebral compression fracture (OVCFs) who were treated with PVP in our hospital from July 2018 to June 2019. These included patients were divided into group A (N = 30) and group B (N = 30). Group A has punctured to the fracture area accurately and injected with a small dose of bone cement, the group B was injected with a conventional dose of bone cement. The operation time, the amount of bone cement injection, the number of X-rays, the VAS scores, the leakage rate of bone cement, and the incidence of adjacent vertebral fractures were compared between the two groups. RESULT: The operation time, fluoroscopic times, and bone cement volume in group A are less than that in group B (P < 0.05). Patients in group A had a lower incidence of cement leakage and adjacent vertebral fracture than that in patients in group B. There was no significant difference in postoperative pain relief between the two groups. CONCLUSIONS: Precise puncture and injection of small doses of bone cement can reduce the number of X-ray fluoroscopy, operation time, amount of bone cement injection, reduce the rate of bone cement leakage and the incidence of adjacent vertebral fractures, which is a safe and effective surgical approach for the treatment for the aged with OVCFs.

Association between breastfeeding and osteoporotic hip fracture in women: a dose-response meta-analysis.

OBJECTIVE: Approximately 300 mg of calcium a day is provided into infants to maintain the physical development of infants, and 5 to 10% bone loss occurs in women during breastfeeding. Hip fractures are considered the most serious type of osteoporotic fracture. We performed this meta-analysis to investigate the association between breastfeeding and osteoporotic hip fractures. MATERIAL AND METHODS: PubMed and Embase were searched until May 1, 2019, for studies evaluating the relationship between breastfeeding and osteoporotic hip fracture in women. The quality of the included studies was evaluated by the methodological index for non-randomized studies (MINORS). For the dose-response meta-analysis, we used the "generalized least squares for trend estimation" method proposed by Greenland and Longnecker to take into account the correlation with the log RR estimates across the duration of breastfeeding. RESULTS: Seven studies were moderate or high quality, enrolling a total of 103,898 subjects. The pooled outcomes suggested that breastfeeding can decrease the incidence of osteoporotic hip fracture (RR = 0.64 (95% CI 0.43, 0.95), P = 0.027). Dose-response analysis demonstrated that the incidence of osteoporotic hip fracture decreased with the increase of breastfeeding time. The RR and 95% CI for 3 months, 6 months, 12 months, and 24 months were RR = 0.93, 95% CI 0.88, 0.98; RR = 0.87, 95% CI 0.79, 0.96; RR = 0.79, 95% CI 0.67, 0.92; and RR = 0.76, 95% CI 0.59, 0.98, respectively, whereas no significant relationship was found between them when the duration of breastfeeding time was more than 25 months. CONCLUSIONS: Our meta-analysis demonstrated that the incidence of osteoporotic hip fracture decreased with the extension of breastfeeding time. However, there is no significant relationship between them when the duration of breastfeeding time was more than 25 months.

Efficacy and safety of tranexamic acid usage in patients undergoing posterior lumbar fusion: a meta-analysis.

BACKGROUND: The purpose of this meta-analysis is to evaluate the efficacy and safety of tranexamic acid (TXA) for patients with degenerative lumbar disc herniation, stenosis or instability undergoing posterior lumbar fusion (PLF) surgery. METHODS: We searched PubMed, Embase, and Cochrane Library until May 1, 2018. Two reviewers selected studies, assessed quality, extracted data, and evaluated the risk of bias independently. Weighted mean difference (WMD) and relative risk (RR) were calculated as the summary statistics for continuous data and dichotomous data, respectively. We chose fixed-effects or random-effects models based on I2 statistics. RevMan 5.0 and STATA 14.0 software were used for data analysis. RESULTS: Nine studies enrolling 713 patients for the study. The pooled outcomes demonstrated that TXA can decrease total blood loss (TBL) in patients underwent PLF surgery [WMD = -250.68, 95% CI (- 325.06, - 176.29), P<0.001], intraoperative blood loss (IBL) [WMD = -72.57, 95% CI (- 103.94, - 41.20), P<0.001], postoperative blood loss (PBL) [WMD = -127.57, 95% CI (- 149.39, - 105.75), P<0.001], and the loss of hemoglobin (Hb) in postoperative 24 h [WMD = -0.31, 95% CI (- 0.44, - 0.18), P<0.001]. However, there is no significant difference between two groups in transfusion rate [RR =0.34, 95% CI (0.09, 1.28), P = 0.11], and none thrombotic event was happened in the two groups. CONCLUSION: Our meta-analysis demonstrated that TXA can decrease the Hb loss, TBL, IBL, PBL, and without increasing the risk of thrombotic event in patients with degenerative lumbar disc herniation, stenosis or instability underwent PLF surgery. However, there was no significant difference in blood transfusion rates between the two groups.

Association between dementia and mortality in the elderly patients undergoing hip fracture surgery: a meta-analysis.

OBJECTIVE: This study was designed to verify the association between dementia and mortality in the elderly undergoing hip fracture surgery, and assessed the mortality of patients with dementia after hip fracture surgery. MATERIAL AND METHODS: PubMed, Embase, and Web of Science were searched until April, 2018 without language restrictions. Two reviewers selected related studies, assessed study quality, and extracted data independently. Risk ratios (RRs) with 95% confidence intervals (CI) were derived using random-effects model throughout all analyses. The endpoints included 30-day, 6-month, 1-year, and more than 1-year mortality. This meta-analysis was performed following PRISMA statement and carried out by using stata14.0 software. RESULTS: Dementia significantly increased postoperative mortality of patients suffered from hip fracture in 30-day [RR = 1.57, 95% CI (1.29, 1.90), P<0.00], 6-month [RR = 1.97, 95% CI (1.47, 2.63), P<0.00], 1-year [RR = 1.77, 95% CI (1.54, 2.04), P<0.00], and more than 1-year follow up [RR = 1.60, 95% CI (1.30, 1.96), P<0.00] respectively. The mortality of dementia patients after hip fracture surgery in 30-day [ES = 12%, 95% CI (8%, 15%)], 6-month [ES = 32%, 95% CI (17%, 48%)], 1-year [ES = 39%, 95% CI (35%, 43%)], and more than 1-year follow up [ES = 45%, 95% CI (32%, 58%)]. CONCLUSIONS: Our meta-analysis demonstrated that the mortality of patients with dementia suffered from hip fracture surgery is 12%, 32%, 39%, and 45%, and dementia increased 1.57, 1.97, 1.77, and 1.60-fold mortality in patients undergoing hip fracture surgery in 30-day, 6-month, 1-year, and more than 1-year follow up respectively.

Efficacy and safety of 3D print-assisted surgery for the treatment of pilon fractures: a meta-analysis of randomized controlled trials.

OBJECTIVE: To compare the effects of 3D print-assisted surgery and conventional surgery in the treatment of pilon fractures. METHODS: PubMed, Embase, Web of Science, CNKI, CBM, and WanFang data were searched until July 2018. Two reviewers selected relevant studies, assessed the quality of studies, and extracted data. For continuous data, a weighted mean difference (WMD) and 95% confidence intervals (CI) were used. For dichotomous data, a relative risk (RR) and 95% CI were calculated as the summary statistics. RESULTS: There were seven randomized controlled trials (RCT) enrolling a total of 486 patients, 242 patients underwent 3D print-assisted surgery and 244 patients underwent conventional surgery. The pooled outcomes demonstrate 3D print-assisted surgery was superior to conventional surgery in terms of operation time [WMD = - 26.16, 95% CI (- 33.19, - 19.14), P < 0.001], blood loss [WMD = - 63.91, 95% CI (- 79.55, - 48.27), P < 0.001], postoperative functional scores [WMD = 8.16, 95% CI (5.04, 11.29), P < 0.001], postoperative visual analogue score (VAS) [WMD = - 0.59, 95% CI (- 1.18, - 0.01), P = 0.05], rate of excellent and good outcome [RR = 1.20, 95% CI (1.07, 1.34), P = 0.002], and rate of anatomic reduction [RR = 1.35, 95% CI (1.19, 1.53), P < 0.001]. However, there was no significant difference between the groups regarding the rate of infection [RR = 0.51, 95% CI (0.20, 1.31), P = 0.16], fracture union time [WMD = - 0.85, 95% CI (- 1.79, 0.08), P = 0.07], traumatic arthritis [RR = 0.34, 95% CI (0.06, 2.09), P = 0.24], and malunion [RR = 0.34, 95% CI (0.06, 2.05), P = 0.24]. CONCLUSIONS: Our meta-analysis demonstrates 3D print-assisted surgery was significantly better than conventional surgery in terms of operation time, blood loss, postoperative functional score, postoperative VAS, rate of excellent and good outcome, and rate of anatomic reduction. Concerning postoperative complications, there were no significant differences between the groups.

A systematic review of tranexamic acid usage in patients undergoing femoral fracture surgery.

BACKGROUND: Patients undergoing femoral fracture surgery frequently require blood transfusion. Tranexamic acid (TXA) has been widely used to decrease transfusion rate in joint replacement surgery. Therefore, we conducted a systematic review to evaluate the efficacy and safety of TXA usage in femoral fracture surgery. MATERIALS AND METHODS: Studies involving TXA usage in femoral fracture surgery were searched through four electronic databases. The end points included total blood loss, postoperative hemoglobin decline, transfusion rate, thromboembolic events, 90-day mortality, and operative time. The present study was performed following Cochrane Reviewers' Handbook and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was carried out by using Stata 14.0 software. RESULTS: Eleven studies concerning intravenous (IV) application of TXA and three studies concerning topical administration of TXA were included. Twelve studies were randomized controlled trials (RCTs), and one was a retrospective cohort study. Regarding IV TXA, our paper indicated that the IV TXA group had less total blood loss (weighted mean difference [WMD] = -319.282, P = 0.000), lower postoperative hemoglobin decline (WMD = -1.14, P = 0.000) and lower transfusion rate (risk difference [RD] = -0.172, P = 0.000). No significant differences were found in thromboembolic events (RD = 0.008, P = 0.507), 90-day mortality (RD = 0.009, P = 0.732) and operative time (WMD = -2.227, P = 0.103). Regarding topical TXA, no significant differences were found in the transfusion rate (RD = -0.098, P = 0.129), postoperative hemoglobin decline (WMD = -1.137, P = 0.231), thromboembolic events (RD = -0.017, P = 0.660) and operative time (WMD = -4.842, P = 0.136). CONCLUSION: Our meta-analysis demonstrated that both IV and topical application of TXA reduced transfusion rate in femoral fracture surgery. However, still further studies are needed to identify the optimal route of administration, TXA dosage and timing. In addition, high-quality RCTs with a large sample size are required to figure out the safety of TXA application, especially in the elderly, before its wide recommendation.

Efficacy and safety of baricitinib for active rheumatoid arthritis in patients with an inadequate response to conventional synthetic or biological disease-modifying anti-rheumatic drugs: A meta-analysis of randomized controlled trials.

The purpose of the present meta-analysis was to assess the efficacy and safety of baricitinib for active rheumatoid arthritis (RA) in patients with an inadequate response or intolerance to conventional synthetic or biological disease-modifying anti-rheumatic drugs (DMARDs). A total of 7 randomized controlled trials (RCTs) were included. The primary effective outcome was the RA improvement to reach an American College of Rheumatology 20% (ACR20) response rate. The safety outcomes were composed of clinical laboratory parameters. All patients included received 4 mg baricitinib once daily to treat RA for 12 or 24 weeks. The ACR20 response rate in the baricitinib group was significantly higher compared with that in the control group at 12 weeks [relative risk (RR), 1.77; 95% confidence interval (CI), 1.62-1.94; P<0.00001] and 24 weeks (RR, 1.76; 95% CI, 1.48-2.10; P<0.00001). Similarly, other effective outcome measures also exhibited significant improvements in the baricitinib group compared with those in the placebo group. Regarding the safety outcomes, no significant difference in adverse events (AEs) was identified at 12 weeks (P=0.14), but AEs were significantly higher in the baricitinib group compared with those in the control group at 24 weeks (P=0.03). Most laboratory values were significantly different between the baricitinib and placebo groups; however, the clinical significance of these changes remains to be determined. In summary, the present meta-analysis demonstrated that 4 mg baricitinib once daily was beneficial in patients with active RA with an inadequate response or intolerance to conventional synthetic or biological DMARDs. More high-quality RCTs are required to determine the sustained efficacy and the safety of baricitinib.

Comparison of navigated and conventional high tibial osteotomy for the treatment of osteoarthritic knees with varus deformity: A meta-analysis.

BACKGROUND: High tibial osteotomy (HTO) is a usefully surgical procedure to correct the malalignment and delay the progression of osteoarthritis. It is still controversy whether navigation system can offer more accuracy of targeted alignment and achieve better clinical outcomes than conventional method. The purpose of present meta-analysis was to investigate whether navigation system was superior to conventional method with regard to clinical and radiographic outcomes. METHOD: The included studies compared the clinical and radiographic outcomes between navigated HTO group and conventional group. The clinical assessments were Lysholm Score, AKS Function Score and Arc of motion, and the radiographic outcomes were Mechanical axis (MA), Weight bearing line ratio (WBL), Outliers of alignment and Change in TPS used to evaluate alignment correction. The meta-analysis was performed using Review Manager 5.3 software. Downs and Black and the Newcastle-Ottawa Scale (NOS) were used to evaluate the study quality. RESULT: Sixteen studies were eligible in present meta-analysis, including thirteen studies concerning opening wedge HTO and three studies involving closing wedge HTO. Clinical outcomes were only reported in studies which used opening wedge HTO. No significant differences were observed in all clinical outcomes between navigated and conventional HTO. Regarding radiographic outcomes, no significant difference in WBL ratio was observed between navigated and conventional HTO. Patients undergoing navigated HTO were associated with significantly greater in MA and lower in Outliers of alignment compared with those undergoing conventional HTO. Compared with conventional HTO, increase in TPS was significantly lower in navigated HTO group using opening wedge HTO, but decrease in TPS was significantly greater in navigated HTO group using closing wedge HTO. CONCLUSION: Our meta-analysis demonstrated that navigated HTO offered more accuracy and precision of alignment correction, except WBL ratio. However, better clinical outcomes were not observed in navigation group.