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Background: Multiple doses of dexamethasone and tranexamic acid can inhibit postoperative inflammation and reduce fibrinolysis and perioperative blood loss in total knee arthroplasty. In this single-center, double-blind, randomized clinical trial, the aim was to investigate whether applying a tourniquet to patients on dexamethasone and tranexamic acid could further reduce perioperative blood loss. Materials and methods: Patients who underwent cemented total knee arthroplasty at our hospital were randomized to receive a tourniquet (n = 71) or not (n = 70) during the procedure. All patients received multiple doses of dexamethasone and tranexamic acid perioperatively. The primary outcome was perioperative blood loss, while secondary outcomes were surgery duration, postoperative laboratory indices of inflammation and fibrinolysis, range of knee motion, VAS pain score, knee circumference, knee swelling rate, homologous transfusion, albumin use, and complications. Results: Using a tourniquet was associated with significantly lower intraoperative blood loss (P < 0.001) and total blood loss (P = 0.007) as well as significantly shorter surgery duration (P < 0.001). In contrast, the tourniquet did not significantly affect hidden blood loss, postoperative inflammation or fibrinolysis, range of knee motion, VAS pain score, knee circumference, knee swelling rate, homologous transfusion, albumin use, or complications. Conclusions: The results of this randomized clinical trial demonstrate that applying a tourniquet during cemented total knee arthroplasty to patients receiving multiple doses of dexamethasone and tranexamic acid can further reduce perioperative blood loss without increasing the risk of inflammation, fibrinolysis, or other complications. Thus, it is advised to use tourniquets combined with dexamethasone and tranexamic acid to reduce perioperative blood loss and avoid tourniquet-related adverse events. Level of evidence: Therapeutic Level I. Trial registration Chinese Clinical Trail Registry, ChiCTR2200060567. Registered 5 June 2022—retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=171291. [ABSTRACT FROM AUTHOR]

A novel injectable hydrogel dressing (GA@AgNPs-SA) with long-term antimicrobial effect is developed that can accelerate the closure of bacteria-infected wounds. The hydrogel dressing was prepared by cross-linking sodium alginate molecular chains and gallic acid functionalized silver nanoparticles (GA@AgNPs) via calcium ions to form a three-dimensional network. The hydrogel dressing demonstrates excellent biocompatibility and can achieve a sustainable release of silver ions, ensuring a long-term antibacterial activity and inhibiting biofilm formation. Moreover, an in vivo study demonstrates that the GA@AgNPs-SA hydrogel can effectively decrease the expression of IL-6 and TNF-α to alleviate the inflammatory response, and promote angiogenesis by upregulating CD31, α-SMA and VEGF expression, thus significantly accelerating the repair of infected wounds. Given these interesting properties, this antibacterial hydrogel has great potential for application in the clinical care of bacteria-infected wounds. [ABSTRACT FROM AUTHOR]

Purpose: Tibetan patients undergoing total knee arthroplasty (TKA) have greater fluctuations in perioperative haemoglobin levels and blood hypercoagulability. This study was to investigate whether ethnicity and altitude affect perioperative blood loss and the risk of complications after TKA., Methods: We retrospectively enrolled 1,116 patients undergoing TKA for knee osteoarthritis at our hospital between January 2016 and September 2021. We divided patients into four groups according to whether they were of Tibetan or Han ethnicity and whether they lived above or below 2500 m above sea level. Primary outcomes were total, intraoperative, and hidden blood losses, while secondary outcomes were complications and homologous transfusion. Factors associated with increased blood loss were analyzed by multivariate regression., Results: Total blood loss was higher among patients residing at high altitude compared with lower altitude, whether they were of Han (794.6 mL vs. 667.2 mL, P = 0.020) or Tibetan (904.4 mL vs. 663.8 mL, P < 0.001). Total blood loss was similar between the two ethnic groups at the same altitude. Altitude, but not Tibetan ethnicity, remained associated with increased blood loss after being analyzed by multivariate regression. Complications among the four groups were generally similar, although the frequency of calf muscular venous thrombosis was higher among Tibetan patients, while the frequency of blood transfusion was higher among Han subjects., Conclusions: Our findings indicate that residence at high altitude, but not ethnicity, may contribute to increased total blood loss during TKA. Thrombotic complications were more frequent among Tibetan than Han patients., (© 2024. The Author(s) under exclusive licence to SICOT aisbl.)

Background: Postoperative nausea and vomiting (PONV) after total joint arthroplasty is common and associated with delayed recovery. This study was performed to evaluate the efficacy of three different prophylactic regimens for PONV after total joint arthroplasty under general anesthesia., Methods: Patients undergoing primary total hip or knee arthroplasty were randomized to Group A (ondansetron), Group B (10 mg dexamethasone plus ondansetron and mosapride), or Group C (three doses of 10 mg dexamethasone plus ondansetron and mosapride). The primary outcome was the total incidence of PONV during postoperative 48 h. The secondary outcomes were complete response, rescue antiemetic treatment, opioid consumption, time until first defecation, postoperative appetite score, satisfaction score, length of hospital stay, blood glucose level, and complications., Results: Patients in Group C experienced a lower incidence of total PONV (29.3%, p = 0.001) and a higher incidence of complete response (70.7%, p = 0.001) than did patients in Group A (51.9%, 48.2%, respectively). Patients in Group C also experienced a lower incidence of severe PONV (4.3%) than patients in Group A (25.9%, p<0.001) and B (20.4%, p<0.001). Moreover, less rescue antiemetic treatment (1.4 ± 0.5 mg Metoclopramide) and postoperative opioid consumption (1.8 ± 0.3 mg Oxycodone, 6.0 ± 1.0 mg Pethidine) was needed in Group C. Additionally, a shorter time until first defecation, shorter length of stay, and better postoperative appetite scores and satisfaction scores were detected in patients in Group C. A slight increase in the fasting blood glucose level was observed in Group C, and the complications were comparable among the groups., Conclusion: Combined use of ondansetron, mosapride and three doses of dexamethasone can provide better antiemetic effectiveness, postoperative appetite, bowel function recovery, and pain relief than a single dose or ondansetron only., Trial Registration Information: The protocol was registered at the Chinese Clinical Trial Registry (ChiCTR1800015896, April 27, 2018)., (© 2024. The Author(s).)

Type 2 diabetes mellitus (T2DM) has become a prevalent public health concern, with beta-cell dysfunction involved in its pathogenesis. Bone marrow adipose tissue (BMAT) increases in both the quantity and area in individuals with T2DM along with heightened monocyte chemotactic protein-1 (MCP-1) secretion. This study aims to investigate the influence and underlying mechanisms of MCP-1 originating from bone marrow adipocytes (BMAs) on systemic glucose homeostasis in T2DM. Initially, a substantial decrease in the proliferation and glucose-stimulated insulin secretion (GSIS) of islet cells was observed. Moreover, a comparative analysis between the control (Ctrl) group and db/db mice revealed significant alterations in the gene expression profiles of whole bone marrow cells, with a noteworthy upregulation of Mcp-1. And the primary enriched pathways included chemokine signaling pathway and AGE-RAGE signaling pathway in diabetic complications. In addition, the level of MCP-1 was distinctly elevated in BMA-derived conditional media (CM), leading to a substantial inhibition of proliferation, GSIS and the protein level of phosphorylated Akt (p-Akt) in Min6 cells. After blocking MCP-1 pathway, we observed a restoration of p-Akt and the proliferation of islet cells, resulting in a marked improvement in disordered glucose homeostasis. In summary, there is an accumulation of BMAs in T2DM, which secrete excessive MCP-1, exacerbating the abnormal accumulation of BMAs in the bone marrow cavity through paracrine signaling. The upregulated MCP-1, in turn, worsens glucose metabolism disorder by inhibiting the proliferation and insulin secretion of islet cells through an endocrine pathway. Inhibiting MCP-1 signaling can partially restore the proliferation and insulin secretion of islet cells, ultimately ameliorating glucose metabolism disorder. It's worth noting that to delve deeper into the impact of MCP-1 derived from BMAs on islet cells and its potential mechanisms, it is imperative to develop genetically engineered mice with conditional Mcp-1 knockout from BMAs., (© 2023. The Author(s).)

Age-associated bone diseases such as osteoporosis (OP) are common in the elderly due to skeletal ageing. The process of skeletal ageing can be accelerated by reduced proliferation and osteogenesis of bone marrow mesenchymal stem cells (BM-MSCs). Senescence of BM-MSCs is a main driver of age-associated bone diseases, and the fate of BM-MSCs is tightly regulated by histone modifications, such as methylation and acetylation. Dysregulation of histone modifications in BM-MSCs may activate the genes related to the pathogenesis of skeletal ageing and age-associated bone diseases. Here we summarize the histone methylation and acetylation marks and their regulatory enzymes that affect BM-MSC self-renewal, differentiation and senescence. This review not only describes the critical roles of histone marks in modulating BM-MSC functions, but also underlines the potential of epigenetic enzymes as targets for treating age-associated bone diseases. In the future, more effective therapeutic approaches based on these epigenetic targets will be developed and will benefit elderly individuals with bone diseases, such as OP., (© 2023. The Author(s).)

Objective: To review the pathological effects of cellular senescence in the occurrence and development of osteoarthritis (OA) and potential therapeutic targets., Methods: The role of chondrocyte senescence, synovial cell senescence, mesenchymal stem cells senescence in OA, and the biological mechanism and progress of chondrocyte senescence were summarized by consulting relevant domestic and abroad literature., Results: The existing evidence has basically made clear that chondrocyte senescence, mesenchymal stem cells senescence, and cartilage repair abnormalities, and the occurrence and development of OA have a certain causal relationship, and the role of the senescence of synovial cells, especially synovial macrophages in OA is still unclear. Transcription factors and epigenetics are the main mechanisms that regulate the upstream pathways of cellular senescence. Signal communication between cells can promote the appearance of senescent phenotypes in healthy cells. Targeted elimination of senescent cells and promotion of mesenchymal stem cells rejuvenation can effectively delay the progress of OA., Conclusion: Cellular senescence is an important biological phenomenon and potential therapeutic target in the occurrence and development of OA. In-depth study of its biological mechanism is helpful to the early prevention and treatment of OA.

Objective: To review and summarize the role and progress of innate immunity in the pathogenesis of osteoarthritis (OA)., Methods: The domestic and foreign literature in recent years was reviewed. The role of innate immune-mediated inflammation, macrophages, T cells, and complement systems in the pathogenesis of OA, potential therapeutic targets, and the latest research progress were summarized., Results: With the deepening of research, OA is gradually considered as a low-grade inflammation, in which innate immunity plays an important role. The polarization of synovial macrophage subpopulation in OA has been studied extensively. Current data shows that the failure of transformation from M1 subtype to M2 subtype is a key link in the progression of OA. T cells and complement system are also involved in the pathological process of OA., Conclusion: At present, the role of innate immunity in the progress of OA has been played in the spotlight, whereas the specific mechanism has not been clear. The macrophage subtype polarization is a potential therapeutic target for early prevention and treatment of OA.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

There is no consensus as to whether drainage tube should be used and how long it should remain in use after primary total knee arthroplasty (TKA). As fast-track (FT) program has been implemented in TKA, whether drainage tube could be removed early, and the ideal timing for removal after FT primary TKA has been a new topic. The purpose of this prospective cohort study was to evaluate the safety and feasibility of early removal of drainage tube when FT program was implemented in primary TKA. A total of 101 patients undergoing FT primary TKA were prospectively allocated into three groups. Patients in group A (31 patients) indwelled wound drainage tube for 6 hours after surgery while group B (34 patients) for 12 hours and group C (36 patients) for 18 hours. The knee circumference, resting and moving visual analogue score (VAS), hemoglobin (Hb), hematocrit, white blood count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), the volume of blood loss and drainage, and postoperative length of stay (LOS) among three groups were recorded and compared. There was no statistically significant difference in the volume of total and hidden blood loss among three groups ( p  > 0.05), but as the time of drainage prolonged, total volume of drainage and dominant blood loss increased gradually ( p  < 0.01). The knee circumference, the mean of resting and moving VAS, Hb, WBC, ESR, CRP, and IL-6 of three groups were similar preoperatively and on postoperative day 1 and 3 ( p  > 0.05), the decrease of Hb in the perioperative period and postoperative LOS as well. Early removal of wound drainage tube could drain the hematocele and reduce the risk of infection, and it doesn't increase the sense of pain, inflammatory reaction, limb swelling, and total blood loss. It's safe and feasible to remove the drainage tube within 6 to 12 hours after FT primary TKA., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To investigate the effectiveness and safety of post-operative retransfusion drain(PRD) after total hip arthroplasty., Methods: A systematic literature review based on PubMed, EMBase, the Cochrane Library, China Biology Medicine disc, CNKI, VIP and WanFang Database in any language regarding PRD following total hip arthroplasty was performed.The data was evaluated using modified Jadad score and then analyzed using RevMan 5.2., Results: Nine randomized controlled trials totaling 1 824 patients, 913 patients in PRD group and 911 in control group, were eligible for data extraction and Meta-analysis.The results indicated that the use of PRD could reduce the requirement of allogeneic blood transfusion when compared with ordinary vacuum drainage (RR=0.61, 95% CI= 0.47-0.79), but the benefit was not found when compared with no drainage group(RR=1.07, 95% CI=0.67-1.71). And the postoperative hemoglobin level was higher in PRD group(MD=0.14, 95% CI=0.01-0.27, P=0.04). No significant difference was identified regarding transfusion index, length of hospital stay, the incidence of febrile reaction and wound-related complications., Conclusions: PRD in reducing requirement of blood transfusion following THA is effective and safe when compared with ordinary vacuum drainage, but the benefit is not found when compared with no drainage.And more robust evidence is needed to confirm this result.