Enhanced Recovery after Total Joint Arthroplasty (TJA): A Contemporary Systematic Review of Clinical Outcomes and Usage of Key Elements.

BACKGROUND: Enhanced recovery after surgery (ERAS) is a pathway designed to improve the care of surgical patients and achieve early recovery. The clinical outcomes and usage of key elements of ERAS pathways in total joint arthroplasty (TJA) need further reanalysis. This article aims to provide an overview of the latest clinical outcomes and current usage of key elements of ERAS pathways in TJA. METHODS: We undertook a systematic review of the PubMed, OVID, and EMBASE databases in February 2022. Studies investigating the clinical outcomes and usage of key elements of ERAS in TJA were included. The components of successful ERAS programs and their usage were further determined and discussed. RESULTS: Twenty-four studies involving 216,708 patients assessed ERAS pathways for TJA. A total of 95.8% (23/24) of studies reported a reduced length of stay (LOS), followed by reduce overall opioid consumption or pain (87.5% [7/8]), save costs (85.7% [6/7]), improvements in patient-reported outcomes or functional recovery (60% [6/10]), and reduced incidence of complications (50% [5/10]). In addition, preoperative patient education (79.2% [19/24]), anesthetic protocol (54.2% [13/24]), use of local anesthetics for infiltration analgesia or nerve blocks (79.2% [19/24]), perioperative oral analgesia (66.7% [16/24]), perioperative surgical factors including reduced use of tourniquets and drains (41.7% [10/24]), use of tranexamic acid (41.7% [10/24]) and early mobilization (100% [24/24]) were contemporary comparatively "active" components of ERAS. CONCLUSIONS: ERAS for TJA has favorable clinical outcomes in terms of reducing LOS and overall pain, saving costs, accelerating functional recovery, and reducing complications, although the evidence is still low in quality. In the current clinical scenario, only some "active" components of the ERAS program are widely used.

Key Elements of Enhanced Recovery after Total Joint Arthroplasty: A Reanalysis of the Enhanced Recovery after Surgery Guidelines.

Recent guidelines have produced a consensus statement for perioperative care in hip and knee replacement. However, there is still a need for reanalysis of the evidence and recommendations. Therefore, we retrieved and reanalyzed the evidence of each recommended components of enhanced recovery after surgery (ERAS) based on the guidelines of total joint arthroplasty. For each one, we included for the highest levels of evidence and those systematic reviews and meta-analyses were preferred. The full texts were analyzed and the evidence of all components were summarized. We found that most of the recommended components of ERAS are supported by evidence, however, the implementation details of each recommended components need to be further optimized. Therefore, implementation of a full ERAS program may maximize the benefits of our clinical practice but this combined effect still needs to be further determined.

Enhancing bone regeneration: advances and innovations in exosome engineering / 中华骨科杂志

Effective bone repair and regeneration is crucial for treating skeletal tissue defects, including osteonecrosis, nonunion fractures, osteoporosis, and various other bone deficiencies. Exosomes, as cellular secretory vesicles, are pivotal in mediating intercellular communication through their cargo of proteins, lipids, and nucleic acids. Mesenchymal stem cell-derived exosomes, in particular, have emerged as promising agents in bone repair and regeneration, showing potential for practical application and clinical translation. Nonetheless, their functional capacity and therapeutic efficacy require enhancement. This review delineates exosome optimization strategies aimed at augmenting secretion and functionality, alongside the incorporation of exosome-functionalized biomaterials for bone healing. Evidence indicates that physical stimulation, molecular interventions, and small-molecule or biomaterial stimuli are effective in increasing exosome output. Moreover, engineering exosomes and their parental cells can further potentiate their therapeutic function. The amalgamation of exosomes with biomaterials represents a burgeoning approach in bone tissue engineering, offering novel therapeutic avenues. This comprehensive analysis aims to guide future applications and the clinical adoption of exosomes in bone tissue restoration.

The effects of Connexin-43 on osteoblasts cells proliferation and osteogenic differentiation / 中华骨科杂志

Objective:To investigate the effects of Connexin-43 (Cx43) on osteoblasts proliferation and osteogenic differentiation and its regulatory mechanism.Methods:Osteoblasts were isolated and cultured in vitro. The osteogenic activity of osteoblasts was detected by alizarin red staining and alkaline phosphatase (ALP) staining after dexamethasone treatment. The expression of Cx43, Runt-related transcription factor 2 (Runx2), ALP, collagen I type (COL-I) and proliferation-related proteins PCNA and CDK4 in osteoblasts were detected by Western-blot. The expressions of osteoblast proteins were detected by immunofluorescence staining. The proliferation of osteoblasts was detected by CCK8 assay. The lentivirus-mediated Cx43 gene overexpression plasmid (Lv-Cx43) was constructed and transfected into osteoblasts. The osteogenic activity and proliferation ability of osteoblasts were further detected by the above methods. Cx43 in osteoblasts was overexpressed by pretreating PD98059. The osteogenic activity and proliferation of Cx43 in overexpressed osteoblasts was detected by CCK8 and alizarin red staining.Results:The isolated osteoblasts have osteogenic differentiation ability. Compared with the control group, 1×10 -6 mol/L dexamethasone treatment could reduce the formation of calcium nodules in osteoblasts. With the increase of dexamethasone treatment duration, the protein expression of Cx43, Runx2, ALP and COL-I in osteoblasts decreased gradually, while the expression of PCNA, CDK4 and p-ERK1/2 decreased. The OD values of normal osteoblasts at 0, 1, 2, 3 and 4 d were 0.316±0.043, 0.891±0.623, 1.683±0.154, 2.315±0.721 and 2.891±0.323, respectively. However, The OD values of osteoblasts treated with dexamethasone were 0.376±0.021, 0.657±0.121, 1.124±0.285, 1.521±0.272, 1.987±0.584, respectively. OD values of dexamethasone treated osteoblasts were lower than those of normal group at 2, 3 and 4 days ( P<0.05). The relative expression levels of Cx43 mRNA in control group, Lv-NC group and Lv-Cx43 group were 0.541±0.086, 0.598±0.018 and 1.000±0.082, respectively. The mRNA expression level of Cx43 in Lv-Cx43 group was higher than that in control group and Lv-NC group ( P<0.05). The ratio of Cx43 protein band to the gray value of GAPDH band in control group, Lv-NC group and Lv-Cx43 group were 0.816±0.737, 0.738±0.643 and 1.145±1.101, respectively. The expression level of Lv-Cx43 was higher than that in control group and Lv-NC group ( P<0.05). The expressions of Runx2, ALP, COL-I mRNA and related marker proteins in Lv-Cx43 group were higher than those in control group and Lv-NC group ( P<0.05). The number of calcium nodules in the Lv-Cx43 group was significantly higher than that in the control group and Lv-NC group. The OD value of osteoblasts and the number of calcium nodules in Lv-Cx43+PD98059 group were significantly lower than those in Lv-Cx43 group ( P<0.05). Conclusion:The proliferation and differentiation ability of osteoblasts is significantly decreased after the treatment of dexamethasone with decreased expression of Cx43. Overexpression of Cx43 can promote the proliferation and osteogenic differentiation of osteoblasts, which may be regulated through the ERK1/2 pathway.

Tranexamic acid attenuates early post-operative systemic inflammatory response and nutritional loss and avoids reduction of fibrinogen in total hip arthroplasty within an enhanced recovery after surgery pathway.

PURPOSE: Total hip arthroplasty (THA) is an intervention with significant inflammatory response. The impact of additional doses of tranexamic acid (TXA) on inflammatory response, trauma and nutrition parameters, and coagulation and fibrinolysis changes has rarely been reported. METHODS: A prospective double-blind randomized trial was performed on elective primary THA. Ninety-nine adult patients were recruited consecutively from 2019 to 2020. They were randomized to receive single-dose of TXA before incision, another dose of TXA at three hours post-operatively, or another two doses of TXA at three and six hours  post-operatively. The primary outcomes included changes in white blood cell (WBC) counts, creatine kinase (CK), haemoglobin(Hb), and albumin(Alb); the secondary outcomes included coagulation and fibrinolysis parameters. RESULTS: Compared with single-dose TXA, patients received three dose TXA had significantly reduced WBC counts and fibrinogen/fibrin degradation product (FDP) levels, increased albumin and fibrinogen levels, and prolonged PT on post-operative day (POD) three. Though patients received three dose TXA had a tendency that increased Hb, decreased CK, reduced D-D, and prolonged APTT on POD3, it is not statistically significant. And the other measured outcomes on POD1 and POD2W shared a similar statistical result, except PT. The PT is significantly prolonged on POD2W in three dose group compared with single dose. CONCLUSION: Three-dose TXA contribute to attenuate early post-operative systemic inflammatory response and nutritional loss, increase fibrinogen, reduce FDP levels, and prolong PT in THA patients within an ERAS pathway, which may associate with reduced early post-operative haemorrhagic tendency, thrombosis risks, and hypercoagulability.

Survivorship and clinical outcomes of 'cup-cage' reconstruction in revision of hip arthroplasty for chronic pelvic discontinuity: A systematic review.

BACKGROUND: This study was conducted to assess the survivorship and clinical outcomes of cup-cage reconstruction technique in the revision of THA. METHODS: PubMed, OVID, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) up to February 2020 were searched. Studies that reported the clinical and radiological follow-up were identified. RESULTS: A total of 151 hips (145 patients) in six studies were included. The all-cause revision-free survivorship of cup-cage implant at the end of follow-up was 90.1% (136/151), with a mean follow-up of 64.4 months(range 12-135). The overall complication rate was 23.8% (36 of 151 hips), of which component problem, dislocation, infection and sciatic nerve palsy/injury were relatively common. All included studies reported improved clinical outcomes at the end of follow-up. CONCLUSION: Results suggested that revision of THA with a cup-cage has a favourable implant survivorship and clinical outcomes for the treatment of pelvic discontinuity, despite the high complications occurrence rates.

Research progress on current status of head-preserving treatment for osteonecrosis of the femoral head and its prognostic factors / 中华骨科杂志

Osteonecrosis of the femoral head (ONFH) is caused by the blockage of the blood supply of the femoral head due to by a variety of reasons, resulting in the death of the bone in the femoral head, which is characterized by osteonecrosis occurdead bone resorption-new bone formation. And total hip arthroplasty (THA) is the final choice for the vast majority of these patients. Though treating hard, it is necessary to choose an appropriate head-preserving treatment in the early stage to delay the time of THA.Methods to treat femoral head necrosis varies, however, it is still hard to have a uniform standard until now. Thus, this paper discusses the epidemiological characteristics, related risk factors, pathology, stage, current head-preserving methods and prognostic factors of femoral head necrosis, so as to further enhance clinicians' understanding of osteonecrosis of the femoral head and provide reference to choose more appropriate head-preserving methods for those patients. As demonstrated in literatures, in China, the incidence of non-traumatic ONFH in males is significantly higher than that in females, and it is more common in northern residents and urban residents. In addition, glucocorticoid intake, hyperlipidemia, heavy smoking and alcohol abuse tend to increase the risk of ONFH; Histologically, osteonecrosis and repair of the femoral head occurred after blood supply was blocked; In terms of pathological staging, Ficat staging is the most commonly used and most directly classification method; core decompression, non-vascularized bone grafting, vascularized bone grafting and osteotomy are still the mainstream surgical methods at present. Patient's age, etiology, stage, etc are important factors affecting the prognosis of ONFH. Therefore, surgeons can choose the most appropriate treatment for the patients according to their specific conditions and prognostic factors.

Study on the expression of connexin-43 in steroid-induced osteonecrosis of femoral head and osteoblasts in rats and its regulation mechanism / 中华骨科杂志

Objective:To investigate the expression of connexin-43 (Cx43) in steroid-induced osteonecrosis of femoral head and osteoblasts in rats and its regulation mechanism.Methods:The model of steroid-induced osteonecrosis of femoral head (SIONFH) of rat was established. Micro-CT and HE staining were used to observe the degree of bone trabecular destruction and the incidence of empty lacunae. The expression levels of Cx43 and PI3K/Akt signaling pathway related molecules and osteoblast-related proteins in model group and control group were detected by RT-PCT and Western blot. The osteoblast (OB) of rats was further isolated and cultured in vitro. Under treatment of dexamethasone (Dex), Cx43 expression in OB cells was detected by Western blot and immunofluorescence. Western blot was used to detect the effect of glucocorticoid (GC) on the expression of related molecules of PI3K/Akt/β-catenin signaling pathway. Akt activator (SC79) and PI3K inhibitor (LY294002) were used to study the molecular mechanism of Dex regulation on Cx43 expression in OB cells. The regulatory relationship between β-catenin and Cx43 was investigated by immunoprecipitation and small interfere RNA (siRNA) technology.Results:The model of SIONFH in rats was successfully established, which proved that Cx43 expression level in the SIONFH model group was significantly lower than that in the control group, and the expression level of Cx43 was positively correlated with the expression of PI3K/Akt signaling pathway related molecules and osteoblast-related proteins Runx2, ALP and Collagen I Type (COL). In addition, in vitro culture of isolated rat OB cells, the expression of Cx43, p-PI3K, P-Akt and β-catenin in OB cells decreased gradually as the Dex action time went on. Moreover, SC79 pretreatment could significantly reverse the inhibitory effect of GCs on Cx43 expression, while LY294002 could significantly enhance the inhibitory effect of GCs on Cx43. In addition, the immunoprecipitation results showed that β-catenin expression was closely related to Cx43 expression, and further studies showed that β-catenin-siRNA could significantly down-regulate the expression of Cx43.Conclusion:Under the action of GC, the expression level of Cx43 in bone tissue and OB cells decreased significantly, and the possible mechanism was that GCs inhibited the expression of Cx43 by inhibiting the PI3K/Akt/β-catenin signaling pathway, which laid a new theoretical foundation for the further study of the role of Cx43 in the pathogenesis of steroid-induced femoral head necrosis.

Mid- to long-term results of modified non-vascularized allogeneic fibula grafting combined with core decompression and bone grafting for early femoral head necrosis.

PURPOSE: The aim of this study was to determine mid-and-long term follow-up results of patients with early femoral head osteonecrosis who were treated by modified free vascularized fibular grafting combined with core decompression and bone grafting. METHODS: Forty-four patients at early ONFH were included in this study. Visual analog scale (VAS) pain scores, range of hip motion (ROM), and Harris hip score (HHS) were recorded to assess the clinical outcome; Western Ontario McMaster Osteoarthritis index (WOMAC) scores and Short Form 36 health survey (SF-36) were conducted to measure the living quality; X-ray film or magnetic resonance imaging (MRI) was used to evaluate radiographic progression; survivorship was defined as patients did not undergo the total hip arthroplasty (THA) or fusion at the last follow-up. Median follow-up was 7.4 years (6-8.2 years). RESULTS: The mean VAS score, ROM, and HHS were significantly improved at the final follow-up compared with preoperative values (p < 0.001). Health assessment including WOMAC scores and SF-36 were also better than those preoperatively (p < 0.001). Seven patients progressed to Ficat III and the four patients progressed to Ficat IV with osteoarthritis. Eight patients who cannot tolerate the pain and had poor living quality underwent THA. CONCLUSION: Modified non-vascularized allogeneic fibula Grafting combined with core decompression and bone grafting could improve the clinical outcomes and enhance the quality of life for patients with early ONFH.

Structural characteristics and biocompatibility of a new nano-Ta-Ti alloy rod fabricated by laser melting technique / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the structural characteristics and biocompatibility of a novel nano-Ta-Ti alloy rod for its potential application in internal fixation.</p><p><b>METHODS</b>Ta coating of a Ti alloy rod with nano-Ta (tantalum) powder was performed using laser melting with symmetrical grooves repleted with nano-Ta powder along the whole length. The microstructure of the cross section of Ta-Ti alloy rod, pore diameter and components of the coating were analyzed using scanning electron microscopy. The influence of this nano-Ta-Ti alloy on proliferation and differentiation of MC3T3-E1 cells was evaluated by MTT cytotoxicity test and ALP activity test.</p><p><b>RESULTS</b>Under scanning electron microscope, the Ta-coating surface presented with a gross porous (200-300 µm) structure with dense fusion between Ta particles, and no new element was produced after laser melting. Biocompatibility evaluation showed that Ti alloys with and without Ta coating both promoted the proliferation of MC3T3-E1 cells, but the coated alloy showed better performance and obviously promoted the differentiation of the osteoblasts.</p><p><b>CONCLUSION</b>Alloying between Ta and Ti can be accomplished successfully by laser melting technique, and the alloy obtained has ideal surface structure and good biocompatibility.</p>

The effect of cytokines on endothelial progenitor cells during angiogenesis / 国际外科学杂志

Endothelial progenitor cells play a significant role in neovascularization of ischemic tissues and in reendothelialization of damaged blood vessels. Cytokines, an important components of micro-environment of angiogenesis,play an important role in regulation of endothelial progenitor cells. The effective application of cytokines can significantly argument the number, enhance the biological function and improve the therapeutic effect of endothelial progenitor cells, which play a positive role in regulation of endothelial progenitor cells.This article briefly reviewed the regulating mechanisms of the vascular endothelial growth factor and other cytokines in a total of 7 endothelial progenitor cells.