Effect of Topical Application of an NSAID Lateral to the Incision on Postoperative Pain Following Unicompartmental Knee Arthroplasty: A Double-Blind Randomized Controlled Trial.

OBJECTIVE: How to minimize postoperative pain following knee replacement surgery has been a great challenge. This study was performed to evaluate the effect of applying a topical nonsteroidal anti-inflammatory drug (NSAID) lateral to the incision for postoperative pain following unicompartmental knee arthroplasty (UKA). METHODS: The randomized controlled trial enrolled 100 patients from August 2023 to January 2024. One hundred patients who underwent UKA were randomized into two groups. The intervention group received a topical NSAID lateral to the incision postoperatively, and the control group received a placebo lateral to the incision postoperatively. The primary outcome measures were the amount of opioid consumption and the visual analogue scale (VAS) score (12, 24, 36, 48, and 72 h after operation) for pain. The secondary outcome measures were the American Knee Society Score (AKSS, preoperation and 1-month follow-up after operation), the time of first analgesic demand, side effects of opioids, operation time, postoperative stay, surgery-related complications, and postoperative incision healing grade. Independent sample t test and paired sample t test were used to compare continuous data. Chi-square test and Fisher's precision probability tests were used to analyze the categorical data. RESULTS: Ninety-eight patients (intervention group, 48 patients; control group, 50 patients) were analyzed. Opioid consumption was significantly lower in the intervention group than in the control group during the first 12 h, 12 to 24 h, and 24 to 48 h postoperatively (p < 0.05). The VAS score for pain within 72 h postoperatively was significantly lower in the intervention group than in the control group (p < 0.05). There was no significant difference in the AKSS, operation time, postoperative stay, complications, or postoperative incision healing grade between the two groups. The time of first analgesic demand for patient-controlled analgesia was significantly later in the intervention group than in the control group (p < 0.05). There were fewer side effects of opioids in the intervention group (8.3%) than in the control group (18.0%). CONCLUSION: Postoperative application of topical NSAIDs lateral to the incision is an effective and safe method for pain management after UKA, helping to decrease the pain score and reduce opioid consumption postoperatively with no increase in side effects.

Unicompartmental knee arthroplasty combined with posterior cruciate ligament reconstruction: a case report.

BACKGROUND: In this study, we present the unique case of a patient with knee osteoarthritis (OA) of the medial compartment and posterior cruciate ligament (PCL) deficiency who underwent simultaneous medial unicompartmental knee arthroplasty (UKA) and PCL reconstruction. CASE PRESENTATION: A 49-year-old male patient presented with a 1-year history of pain and instability in the left knee. The patient had previously experienced a trauma-related injury to the PCL of the left knee that was left untreated. Imaging and physical examination confirmed the presence of left medial knee OA along with PCL rupture. To address these issues, the patient underwent UKA combined with PCL reconstruction. The patient's Lysholm score was 47 before surgery and 81 three months after surgery, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was 29 before surgery and 18 three months after surgery, and the International Knee Documentation Committee (IKDC) subjective score was 56.3 before surgery and 74.7 three months after surgery. Six months after surgery, the patient's gait returned to normal, and he was able to jog. CONCLUSION: This case report presents the first instance of UKA combined with PCL reconstruction and introduces a novel treatment approach for patients suffering from medial knee OA and ligament injury.

Effect of Perineural or Intravenous Betamethasone on Femoral Nerve Block Outcomes in Knee Arthroplasty: A Randomized, Controlled Study.

OBJECTIVES: Despite the use of multimodal analgesia, patients undergoing knee arthroplasty still encounter residual moderate pain. The addition of betamethasone to local anesthetic has been shown to improve postoperative pain. However, it remains uncertain whether the positive effects of perineural or intravenous administration of betamethasone on analgesia outcomes lead to better early mobility and postoperative recovery. METHODS: Between June 2022 and February 2023, a total of 159 patients who were undergoing knee arthroplasty were included in this study. These patients were allocated randomly into three groups: (i) the NS group, received ropivacaine 0.375% and intravenous 3mL 0.9% normal saline; (ii) the PNB group, received ropivacaine 0.375% plus perineural betamethasone (12mg) 3mL and intravenous 3mL 0.9% normal saline; and (iii) the IVB group, received ropivacaine 0.375% and intravenous betamethasone (12mg) 3mL. RESULTS: Both perineural and intravenous administration of betamethasone led to improved median (IQR) numeric rating scale (NRS) scores on the 6-meter walk test, with a score of 1.0 (1.0-2.0) for both groups, compared with 2.0 (1.0-2.0) for the NS group (p = 0.003). Compared to the NS group, both the PNB and IVB groups showed significant reductions in NRS scores at 24 and 36 h after surgery, along with a significant increase in ROM at 24, 36, and 48 h post-operation. Additionally, it exhibited lower levels of cytokine IL-1ß and TNF-α in fluid samples, as well as lower level of HS-CRP in blood samples in the PNB and IVB groups compared to the NS group. CONCLUSION: The administration of perineural and intravenous betamethasone demonstrated an enhanced analgesic effect following knee arthroplasty. Furthermore, it was associated with reduced levels of IL-1ß, TNF-α, and HS-CRP, as well as enhanced knee ROM, which is conducive to early ambulation and postoperative rehabilitation after knee arthroplasty.

Effect of Bone Cement Thickness on the Risk of Scalded Skin in Joint Surgery.

OBJECTIVE: Bone cement releases a large amount of heat as it polymerizes. Skin burns caused by discarded bone cement are not well understood during arthroplasty. It is important to study the correlates and mechanisms of scalding and to accurately evaluate the severity of burns to guide treatment decisions. METHODS: Standardized burns were created in eight anesthetized rabbits using different thicknesses of bone cement. Bone cement was uniformly stirred to make thicknesses of 1 mm, 4 mm, 8 mm, 12 mm, 16 mm, and 20 mm and a 20 × 40 mm cuboid. Bone cement samples were then placed on the back of a rabbit, and the temperature changes were recorded with an industrial digital thermometer. One hour later, the appearance of scalded skin was observed, and the rabbits were euthanized. The scalded parts were cut to make pathological sections and stained with HE, and the differences in the depth of the scalded skin caused by different thicknesses of bone cement were observed under a light microscope. RESULTS: Damage caused by 1 mm-, 4 mm-, 8 mm-, 12 mm-, 16 mm-, and 20 mm-thick bone cement samples mainly involved the epidermis, the papillary dermis, the reticular dermis layer, and the full thickness of the skin and the subcutaneous tissue. The maximum temperature of 1 mm, 4 mm, 8 mm, and 12 mm bone cementation had a statistically significant difference (p < 0.001), while there was no significant difference between 12 mm, 16 mm, and 20 mm samples (p = 0.856). The time to severe scalding with bone cement at temperatures above 70°C was significantly different between different thicknesses (p < 0.001). CONCLUSION: The heat released by different thicknesses of bone cement leads to different maximum temperatures and the duration of severe burns, resulting in different degrees of skin burns. Attention should be paid to discarded bone cement to prevent this potential complication in knee arthroplasty.

Intra-Articular Injection of Autologous Micro-Fragmented Adipose Tissue for the Treatment of Knee Osteoarthritis: A Prospective Interventional Study.

BACKGROUND: To investigate the efficacy and safety of autologous micro-fragmented adipose tissue (MF-AT) for improving joint function and cartilage repair in patients with knee osteoarthritis. METHODS: From March 2019 to December 2020, 20 subjects (40 knees) between 50 and 65 years old suffering from knee osteoarthritis were enrolled in the study and administered a single injection of autologous MF-A. The data of all patients were prospectively collected. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), knee society score (KSS), hospital for special surgery (HSS) score, visual analogue score (VAS) pain score, changes in cartilage Recht grade on magnetic resonance imaging (MRI) and adverse events were analyzed before and 3, 6, 9, 12 and 18 months after injection. RESULTS: The WOMAC, VAS, KSS and HSS scores at 3, 6, 9, 12 and 18 months after injection were improved compared with those before injection (p < 0.05). There was no significant difference in WOMAC scores between 9 and 12 months after injection (p > 0.05), but the WOMAC score 18 months after injection was worse than that at the last follow-up (p < 0.05). The VAS, KSS and HSS scores 9, 12 and 18 months after injection were worse than those at the last follow-up (p < 0.05). The Recht score improvement rate was 25%. No adverse events occurred during the follow-up. CONCLUSIONS: Autologous MF-AT improves knee function and relieves pain with no adverse events. However, the improved knee function was not sustained, with the best results occurring 9-12 months after injection and the cartilage regeneration remaining to be investigated.

The validity and accuracy of 3D-printed patient-specific instruments for high tibial osteotomy: a cadaveric study.

OBJECTIVE: High tibial osteotomy (HTO) has been used for the treatment of patients with knee osteoarthritis. However, the successful implementation of HTO requires precise intraoperative positioning, which places greater requirements on the surgeon. In this study, we aimed to design a new kind of 3D-printed patient-specific instrument (PSI) for HTO, including a positioning device and an angle bracing spacer, and verify its effectiveness using cadaveric specimens. METHODS: This study included ten fresh human lower-limb cadaveric specimens. Computed tomography (CT) and X-ray examinations were performed to make preoperative plans. PSI was designed and 3D-printed according to the preoperative plan. Then, the PSI was used to guide HTO. Finally, we performed X-ray and CT after the operation to verify its validity and accuracy. RESULTS: The PSI using process was adjusted according to the pre-experimental procedure in 1 case. Hinge fracture occurred in 1 case. According to X-rays of the remaining eight cadaveric specimens, no statistically significant difference was noted between the preoperative planning medial proximal tibial angle (MPTA) and postoperative MPTA (P > 0.05) or the preoperative and postoperative posterior slope angle (PSA) (P > 0.05). According to the CT of 10 cadaveric specimens, no statistically significant difference was noted between the design angle and actual angle, which was measured according to the angle between the osteotomized line and the cross section (P > 0.05). The gap between the designed osteotomy line and the actual osteotomy line was 2.09 (0.8 ~ 3.44) mm in the coronal plane and 1.58 (0.7 ~ 2.85) mm in the sagittal plane. CONCLUSION: This 3D-printed PSI of HTO accurately achieves the angle and position of the preoperative plan without increasing the stripping area. However, its use still requires a certain degree of proficiency to avoid complications, such as hinge fracture.

Drainage relieves pain without increasing post-operative blood loss in high tibial osteotomy: a prospective randomized controlled study.

PURPOSE: Drainage is a common procedure in high tibial osteotomy (HTO), but the benefits of drainage during HTO remain poorly investigated. This study was designed to investigate the effect of drainage on blood loss and early functional recovery in HTO. METHODS: Altogether, 80 patients undergoing HTO were analyzed from August 2018 to September 2019. Patients were randomized into two groups: group A (drainage, n = 40) and group B (no drainage, n = 40). There were no intergroup differences in baseline parameters between the two groups, and the same surgical techniques and haemostatic methods were used. The mean follow-up time was 3.2 months. Blood loss and early functional recovery of the knee were examined post-operatively in both groups. RESULTS: The total post-operative blood loss was 253.34 ± 104.18 ml in group A and 222.51 ± 106.89 ml in group B. This difference was non-significant (p > 0.05). The post-operative haemoglobin and haematocrit differences between groups were also non-significant (p > 0.05). Post-operative visual analogue scale (VAS) pain scores and lower leg swelling were lower in group A than those in group B (p < 0.05), and the early range of motion of the knee joint was higher in group A than that in group B (p < 0.05). Group A had lower incidence rates of dressing seepage and incision complications than group B (p < 0.05). The differences in three month post-operative VAS and knee function scores were non-significant (p > 0.05). CONCLUSION: Drainage in HTO does not increase patients' total blood loss, but it can promote early knee function recovery by reducing post-operative pain, lower leg swelling, and the incidence of incision complications. TRIAL REGISTRATION: NCT-03954860.

Intravenous Combined with Topical Tranexamic Acid Administration Has No Additional Benefits Compared with Intravenous Administration Alone in High Tibial Osteotomy: A Retrospective Case-Control Study.

OBJECTIVE: To investigate whether intravenous combined with topical administration of tranexamic acid (TXA) is superior to intravenous administration alone in terms of blood loss, incision complications, functional recovery, and pain relief in high tibial osteotomy (HTO). METHODS: Clinical data of patients with knee osteoarthritis (OA) treated with unilateral HTO were retrospectively reviewed. The patients were grouped according to the TXA administration method, with 24 patients in the combined group and 21 in the solo group. In the combined group, 100 mL saline containing 1 g TXA was intravenously administered before application of a tourniquet, and 20 mL saline containing 2 g TXA was injected through a drainage tube after closure of the incision. Alternatively, 100 mL of saline containing 1 g TXA was intravenously administered before application of a tourniquet in the solo group. The blood loss and adverse events were compared between the two groups. RESULTS: All patients were followed for more than half a year. The drainage volume on the first day and total blood loss on the second day after surgery in the combined and single treatment groups were 130.06 ± 29.22 and 165.35 ± 43.08 mL (P < 0.05), respectively, and 327.17 ± 64.26 and 385.45 ± 63.31 mL (P < 0.05). There were no blood transfusions in either group. One case of delayed incision healing was observed in the solo group, and no such event occurred in the combined group. There were no significant differences between the two groups in terms of the following factors: the activated partial thromboplastin time (APTT) and prothrombin time (PT); levels of fibrinogen (FIB) and D-dimer on the second day after surgery; numbers of hospitalization days and thromboembolism events; and knee joint function and visual analog score 6 months after surgery. CONCLUSION: Intravenous combined with topical TXA administration in HTO is superior to intravenous administration alone for reducing postoperative blood loss and drainage volume without thromboembolic complications. However, even with only intravenous TXA administration, no cases of blood transfusion and only 1 case of incision complication occurred. At the same time, the combined use of TXA did not improve the recovery of knee joint function and pain relief after HTO.

TRIM3 Negatively Regulates Autophagy Through Promoting Degradation of Beclin1 in Ewing Sarcoma Cells.

BACKGROUND AND AIM: Ewing sarcoma (ES) is an aggressive neoplasm predominantly occurring in adolescents and has a poor prognosis when metastasized. In the current study, we were aiming to investigate the function of TRIM3 in autophagy in ES cells. METHODS: The expression of TRIM3 in Ewing sarcoma tissues and normal tissues was examined by quantitative PCR and western blot. The effect of TRIM3 on autophagy was detected by western blot and immunofluorescence assay. Target of TRIM3 was examined by western blot, immunoprecipitation and ubiquitination assay. RESULTS: We found the expression of TRIM3 was significantly up-regulated in Ewing sarcoma tissues compared with normal tissues, and this phenomenon was regulated by EWS-FLI1 expression. Furthermore, we observed that overexpression of TRIM3 markedly and consistently inhibited autophagy in ES cells, and autophagy was enhanced in TRIM3-silenced ES cells. Finally, we found in ES cells, TRIM3 could directly interact with Beclin1, and improved its K48-linked polyubiquitinaion, leading to the degradation of Beclin1 and then regulated autophagy. CONCLUSION: In the present research, for the first time we revealed that TRIM3 negatively regulates autophagy through promoting degradation of Beclin1 in Ewing sarcoma cells, and these findings may provide ideas for ES research.

MicroRNA­34b promotes proliferation, migration and invasion of Ewing's sarcoma cells by downregulating Notch1.

Ewing's sarcoma is the second most frequent bone and soft tissue sarcoma, which is commonly driven by the Ewing's sarcoma breakpoint region 1­friend leukemia integration 1 transcription factor (EWS­FLI1) fusion gene. Since microRNAs (miRs) can act as either oncogenes or tumor suppressor genes in human cancer, and miR­34b has been reported to act as a tumor suppressor, the role of miR­34b in Ewing's sarcoma was investigated in the present study. The results demonstrated that miR­34b expression levels were higher in tumor samples compared within normal tissue samples. Notably, miR­34b expression levels were significantly higher in EWS­FLI1­positive samples compared within EWS­FLI1­negative samples. The effects of miR­34b expression on cell proliferation, migration and invasion were also examined. miR­34b expression was inhibited using small interfering (si)RNA targeting the fusion gene. Transfection of a miR­34b precursor sequence into siRNA­treated tumor cells resulted in a significant increase in cell growth, migration and invasion compared within the control group. In addition, the adhesive ability was increased in the Ewing's sarcoma cell line RD­ES, but not A673, following miR­34b upregulation. Conversely, downregulation of miR­34b expression led to a significant decrease in cell growth, migration and invasion. Notch has previously been reported to serve either oncogenic or tumor suppressive roles in human cancer. The results indicated that Notch1 and its target genes, Hes family BHLH transcription factor 1 and Hes­related family BHLH transcription factor with YRPW motif 1, were suppressed by miR­34b directly In conclusion, EWS­FLI1 may modulate miR­34b expression directly or indirectly, and miR­34b potentially has an oncogenic role in Ewing's sarcoma by downregulating Notch1.

EWS-FLI1 positively regulates autophagy by increasing ATG4B expression in Ewing sarcoma cells.

Ewing sarcoma (ES) is the most common malignant bone tumor in children and young adults. It is characterized by chromosomal translocations fusing the EWS gene with an ETS oncogene, most frequently FLI1. In the present study, the authors aimed to investigate the function of EWS-FLI1 in autophagy in ES cells, and identified that EWS-FLI1 positively regulates autophagy in ES cells. ATG4B expression was observed markedly upregulated by EWS-FLI1 overexpression, and silencing of ATG4B dramatically inhibits autophagy in ES cells. Furthermore, apoptosis was inhibited in ATG4B overexpressed ES cells, and ATG4B-potentiated autophagy is required for ES cells survival. Taken together, the authors demonstrated the role of EWS-FLI1 and ATG4B in autophagy in ES cells, and suggested EWS-FLI1 and ATG4B as potential therapeutic targets for ES.

Effects of Unilateral Tourniquet Used in Patients Undergoing Simultaneous Bilateral Total Knee Arthroplasty.

OBJECTIVE: To assess the benefits of use of a tourniquet in one limb in patients undergoing simultaneous bilateral total knee arthroplasty (TKA). METHODS: A prospective randomized trial was designed to evaluate the outcomes of unilateral tourniquet use during simultaneous bilateral TKA. A total of 52 (36 women and 16 men) patients with osteoarthritis who underwent simultaneous bilateral primary TKA between January 2010 and January 2015 were assigned randomly to tourniquet (TG) or non-tourniquet (NG) groups prior to surgery. Operating time, pain score, range of motion, first active straight-leg raise time, swelling, wound healing, deep vein thrombosis, and Knee Society score were observed. RESULTS: Mean operating time in the TG group was shorter than that in the NG group (P < 0.05). Postoperative pain was measured by a visual analog scale (VAS) and straight-leg raise time, which was lower and shorter in limbs operated without the use of a tourniquet (P < 0.05). In addition, this group had less postoperative swelling and lower incidence of wound complications in the early postoperative period (P < 0.05). There was no significant difference in the range of motion (ROM), deep venous thrombosis incidence, and Knee Society scores between the two groups. CONCLUSIONS: Tourniquet use in bilateral TKA can reduce intraoperative time but was associated with a higher incidence of wound complications and larger postoperative knee swelling.

Bortezomib induces apoptosis and autophagy in osteosarcoma cells through mitogen-activated protein kinase pathway in vitro.

OBJECTIVE: To investigate the effects of bortezomib on human osteosarcoma cells from the HOS cell line, and the underlying associated mechanisms. METHODS: Viability of HOS cells treated with bortezomib (5-20 nM) for different time periods was measured and changes in the cell cycle were assessed. Apoptosis and autophagy in HOS cells treated with bortezomib were analysed using annexin V-fluorescein isothiocyanate assay, transmission electron microscopy and Western blotting. Surges in mitogen-activated protein kinase (MAPK) pathways including MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK1/2), ERK1/2, c-Jun N-terminal kinase (JNK) and p38 MAPK were analysed using Western blotting. RESULTS: Bortezomib induced growth inhibition in a time- and dose-dependent manner, and autophagy and apoptosis in a dose-dependent manner, in HOS cells. HOS cell autophagy and apoptosis in response to bortezomib, corresponded with changing levels of intracellular MAPK signalling molecules. CONCLUSIONS: This study provided new insights into the mechanisms underlying bortezomib-induced apoptosis in human osteosarcoma HOS cells, and suggests that bortezomib could be a potent chemotherapeutic agent in the treatment of osteosarcoma.

Prognostic significance of cyclooxygenase-2 in osteosarcoma: a meta-analysis.

Published studies researching the prognostic significance of cyclooxygenase-2 (COX-2) expression in patients with osteosarcoma are inconclusive and heterogeneous. We conducted a meta-analysis to assess its prognostic value more precisely. The pooled odds ratios (ORs) or hazard ratios (HRs) with corresponding 95 % confidence intervals (CIs) were calculated to evaluate the effects. Fourteen studies with 735 osteosarcoma patients were included to estimate the relationship between COX-2 and metastasis of tumor, clinical stage, and 3-year overall survival. High expressions of COX-2 predicted neoplasm metastasis (OR = 1.891, 95 % CI 1.276-2.803, P = 0.002), advanced clinical stage (OR = 1.801, 95 % CI 1.257-2.581, P = 0.001). In addition, high COX-2 expression tended to be associated with a poor 3-year survival (HR = 1.741, 95 % CI 0.762-3.979, P = 0.188), but the difference was not significant. Therefore, this meta-analysis demonstrated that high COX-2 expression might be an unfavorable prognostic effect in osteosarcoma.

Smad3 is the key to transforming growth factor-ß1-induced osteoclast differentiation in giant cell tumor of bone.

Giant cell tumor (GCT) of bone is a benign but locally aggressive neoplasm of bone. However, molecular mechanisms underlying osteolysis in GCT have not been deeply understood. The aim of this study was to investigate one of the possible mechanisms underlying the up-regulation of receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG) expression. First, we performed an immunohistochemical study on transforming growth factor-ß1 (TGF-ß1) expression in 83 cases with GCT and found that increased TGF-ß1 staining was significantly correlated with Campanacci stages(Spearman's correlation = 0.335, p = 0.002). Next, we investigated the mechanism of the effect of TGF-ß1 on osteolysis of GCT and examined the effects of TGF-ß1 plus or minus specific inhibitor of Smad3 (SIS3) on the expression of RANKL/OPG ratio at the mRNA and protein levels in two primary GCT cell lines. The results clearly indicated that TGF-ß1 is capable of significantly increasing RANKL/OPG ratio (p GCT1 = 0.000, p GCT2 = 0.000) and that SIS3 is capable of reversing the ratio, suggesting that Smad3 is the key to TGF-ß1-induced increased the ratio. In the co-culture system, we found that SIS3 reversed the effects of TGF-ß1-induced osteoclast formation in the co-culture system (p GCT1 = 0.000, p GCT2 = 0.000). Our findings indicate that TGF-ß1 plays an important role in the osteolysis of GCT via Smad3.

Differential expression of the RANKL/RANK/OPG system is associated with bone metastasis in human non-small cell lung cancer.

BACKGROUND: Human non-small cell lung cancer (NSCLC) patients exhibit a high propensity to develop skeletal metastasis, resulting in excessive osteolytic activity. The RANKL/RANK/OPG system, which plays a pivotal role in bone remodeling by regulating osteoclast formation and activity, is of potential interest in this context. MATERIALS AND METHODS: Reverse transcriptase polymerase chain reaction, western blotting, and immunohistochemical analysis were used to examine the expression of RANKL, RANK, and OPG in human NSCLC cell lines with different metastatic potentials, as well as in 52 primary NSCLC samples and 75 NSCLC bone metastasis samples. In primary NSCLC patients, the expression of these proteins was correlated with clinicopathological parameters. Recombinant human RANKL and transfected RANKL cDNA were added to the PAa cell line to evaluate the promoter action of RANKL during the process of metastasis in vitro and in vivo. RESULTS: Up-regulated RANKL, RANK, and OPG expression and increased RANKL:OPG ratio were detected in NSCLC cell lines and in tumor tissues with bone metastasis, and were correlated with higher metastatic potential. The metastatic potential of NSCLC in vitro and in vivo, including migration and invasion ability, was significantly enhanced by recombinant human RANKL and the transfection of RANKL cDNA, and was impaired after OPG was added. The increased expression of RANKL and OPG correlated with tumor stage, lymph node metastasis, and distant metastasis. CONCLUSIONS: Differential expression of RANKL, RANK, and OPG is associated with the metastatic potential of human NSCLC to skeleton, raising the possibility that the RANKL/RANK/OPG system could be a therapeutic target for the treatment of metastatic NSCLC patients.