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This study aimed to explore the analgesic effect among adductor canal block (ACB) combined with infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) block, ACB, and IPACK block following total knee arthroplasty (TKA).One hundred twenty patients were randomly allocated into 3 groups including group A (ACB + IPACK block), group B (ACB), and group C (IPACK block). The primary outcome was postoperative pain score. The secondary outcome was opioid consumption. Other outcomes included functional evaluation and postoperative complications.Group A showed the lowest pain scores within 8 hours at rest and with knee maximum flexion (P.001). From 12 to 24 hours, group C showed the highest pain scores, while no significant difference was found between group A and group B. No significant difference was found among the 3 groups 24 hours postoperatively. Group C showed the most opioid consumption within the first 24 hours and during the hospitalization, while no significant difference was found between group A and group B. No significant difference was found among the 3 groups including function evaluation and postoperative complications.ACB + IPACK block can improve early analgesia when compared with ACB. However, the small statistical benefit to the addition of IPACK block to ACB may be unlikely to be clinically significant. Further studies may focus on patient selection and how to prolong the effect of IPACK block.

Background Bilateral osseous ankylosed hips secondary to ankylosis spondylitis (AS) are relatively rare but impact the quality of life hugely. Cementless total hip arthroplasty (THA) for bilateral osseous ankylosed hips with AS is a challenging procedure. No previous literature compares the clinical outcomes of synchronous and sequential bilateral THA for these special patients. Methods 23 patients (46 hips) were retrospectively analyzed and divided into bilateral THA synchronously (group A) and sequentially (group B). The clinical measurement, radiological assessments, and complications were compared. Independent sample T test was used for data analysis. Results Harris Hip Scores (HHS) improved greatly for both groups (P = 0.58) as well as the range of motion (P = 0.64). But group B can realize shorter time (3.6 ± 1.2 days) to walk for the first time postoperatively (P = 0.02). Group A needed more blood transfusions (P = 0.028). For group A, no statistical difference was found in the bilateral inclination of cup (IC) (P = 0.48) and femoral offset (FO) (P = 0.07). For group B, no statistical difference was observed in bilateral IC (P = 0.37) but in bilateral FO (P = 0.04). Group A showed the fewer difference of bilateral IC (P = 0.02), while comparative measurements were found for two groups in the difference of bilateral FO (P = 0.78) and leg length discrepancy (P = 0.83). For both groups, the total hospital expense for each patient was similar and almost all patients were very satisfied with the outcomes. For group A, one patient encountered femoral fracture intraoperatively and another patient encountered hip dislocation and delay union of wound. 3 hips from group A and 3 hips from group B encountered heterotopic ossification. Conclusions Our retrospective research demonstrated that cementless bilateral THA was a reliable treatment for osseous ankylosed hip due to AS. Synchronous and sequential bilateral THA can realize similarly satisfactory clinical outcomes and radiographic evaluation.

Objective To investigate whether the risk of dislocation after total hip arthroplasty (THA) in patients with Crowe type IV developmental dysplasia of the hip (DDH) is high and to further identify the risk factors for postoperative dislocation in these patients. Methods This retrospective cohort study reviewed Crowe type IV DDH patients undergoing THA between January 2009 and December 2017 in our institution. Each Crowe type IV DDH patient was matched with three Crowe type I, II, or III DDH patients according to gender, side and date of operation. The primary outcome of this study was postoperative dislocation after THA. Occurrence, rate, classification, treatment and outcome of dislocation were documented in detail for all patients. The dislocation rates were compared between Crowe type IV DDH patients and Crowe type I, II, or III DDH patients. Demographic data, implant factors, and surgical factors were compared between the dislocation and no dislocation groups. Multiple logistic regression analysis was used to determine the independent risk factors for dislocation in Crowe type IV hips. Results A total of 131 Crowe type IV hips were followed up for a mean of 76.5 ± 28.1 months. Three hundred and ninety‐three Crowe type I, II and III hips, including 261 type I hips, 94 type II hips, and 38 type III hips, were identified as controls and followed up for a mean of 76.4 ± 28.2 months. No significant difference was observed in follow‐up time between two groups (P = 0.804). One or more dislocations occurred in 22 of the 524 dysplasia hips (4.20%). Of the 22 dislocated hips, 20 hips (90.9%) were successfully managed with non‐operative treatment. Two patients (9.1%, one Crowe type I and one Crowe type IV) experienced recurrent dislocation and required revision surgery. Crowe type IV hips had a significantly higher postoperative dislocation rate than type I, II, and III hips (11.45% vs 1.78%, P

Background The purpose of this study is to analyze the 10-year outcomes of cementless, modular total hip arthroplasty (THA) in adult patients who had high dislocation secondary to childhood pyogenic arthritis. Methods We retrospectively followed 56 consecutive patients who underwent cementless, modular THA for the late sequelae of childhood septic arthritis of the hip from 2001 to 2011. There were 23 men and 33 women with a mean age of 47 years (24 to 68). Of the 56 hips, 25 were classified as Crowe type III and 31 as type IV. Mean follow-up was 10.7 years. Results One hip with a quiescent period of 23 years had recurrence of infection. Revision surgery was performed in 2 patients because of loosening and breakage of femoral stem and new infection with no correlation with childhood sepsis, respectively. The mean Harris hip scores improved from 44.2 points preoperatively to 87.5 points at final follow-up. Similarly, the Hip dysfunction and Osteoarthritis Outcome Score and hip pain also significantly improved at the latest follow-up. The mean acetabular cup abduction was 40.8° and the mean anteversion 27.8°, respectively. There were 5 cases of transient nerve palsy and 5 cases of intraoperative fracture. Conclusion THA can reliably restore the abnormal anatomy and provide good results in these young and active patients who had high hip dislocation secondary to childhood pyogenic arthritis with a relatively high incidence of complications. However, these complications can be treated.

BackgroundNontraumatic osteonecrosis of the femoral head (NONFH) is a devastating disease, and the risk factors associated with progression into collapse after core decompression (CD) remain poorly defined. Therefore, we aim to define risk factors associated with collapse-free survival (CFS) after CD of precollapse NONFH and to propose a nomogram for individual risk prediction.MethodsAccording to the baseline characteristics, clinical information, radiographic evaluations, and laboratory examination, a nomogram was developed using a single institutional cohort of patients who received multiple drilling for precollapse NONFH between January 2007 and December 2019 to predict CFS after CD of precollapse NONFH. Furthermore, we usedCstatistics, calibration plot, and Kaplan-Meier curve to test the discriminative ability and calibration of the nomogram to predict CFS.ResultsOne hundred and seventy-three patients who underwent CD for precollapse NONFH were retrospectively screened and included in the present study. Using a multiple Cox regression to identify relevant risk factors, the following risk factors were incorporated in the prediction of CFS: acute onset of symptom (HR, 2.78; 95% CI, 1.03–7.48;P= 0.043), necrotic location of Japanese Investigation Committee (JIC) C1 and C2 (HR, 3.67; 95% CI, 1.20–11.27;P= 0.023), necrotic angle in the range of 250–299°(HR, 5.08; 95% CI, 1.73–14.93;P= 0.003) and > 299° (HR, 9.96; 95% CI, 3.23–30.70;P< 0.001), and bone marrow edema (BME) before CD (HR, 2.03; 95% CI, 1.02-4.02;P= 0.042). TheCstatistics was 0.82 for CFS which revealed good discriminative ability and calibration of the nomogram.ConclusionsIndependent predictors of progression into collapse after CD for precollapse NONFH were identified to develop a nomogram predicting CFS. In addition, the nomogram could divide precollapse NONFH patients into prognosis groups and performed well in internal validation.

Background: In this study, we investigated the in vitro and in vivo chondrogenic capacity of kartogenin (KGN)–enhanced bone marrow–derived mesenchymal stem cells (BMSCs) for cartilage regeneration. Purpose: To determine (1) whether functionalized nanographene oxide (NGO) can effectively deliver KGN into BMSCs and (2) whether KGN would enhance BMSCs during chondrogenesis in vitro and in vivo in an animal model. Study Design: Controlled laboratory study. Methods: Functionalized NGO with line chain amine-terminated polyethylene glycol (PEG) and branched polyethylenimine (BPEI) were used to synthesize biocompatible NGO-PEG-BPEI (PPG) and for loading hydrophobic KGN molecules noncovalently via π–π stacking and hydrophobic interactions (PPG-KGN). Then, PPG-KGN was used for the intracellular delivery of hydrophobic KGN by simple mixing and co-incubation with BMSCs to acquire KGN-enhanced BMSCs. The chondrogenic efficacy of KGN-enhanced BMSCs was evaluated in vitro. In vivo, osteoarthritis (OA) was induced by anterior cruciate ligament transection in rats. A total of 5 groups were established: normal (OA treated with nothing), phosphate-buffered saline (PBS; intra-articular injection of PBS), PPG-KGN (intra-articular injection of PPG-KGN), BMSCs (intra-articular injection of BMSCs), and BMSCs + PPG-KGN (intra-articular injection of PPG-KGN–preconditioned BMSCs). At 6 and 9 weeks after the surgical induction of OA, the rats received intra-articular injections of PPG-KGN, BMSCs, or KGN-enhanced BMSCs. At 14 weeks after the surgical induction of OA, radiographic and behavioral evaluations as well as histological analysis of the knee joints were performed. Results: The in vitro study showed that PPG could be rapidly uptaken in the first 4 hours after incubation, reaching saturation at 12 hours and accumulating in the lysosome and cytoplasm of BMSCs. Thus, PPG-KGN could enhance the efficiency of the intracellular delivery of KGN, which showed a remarkably high chondrogenic differentiation capacity of BMSCs. When applied to an OA model of cartilage injuries in rats, PPG-KGN–preconditioned BMSCs contributed to protection from joint space narrowing, pathological mineralization, OA development, and OA-induced pain, as well as improved tissue regeneration, as evidenced by radiographic, weightbearing, and histological findings. Conclusion: Our results demonstrate that KGN-enhanced BMSCs showed markedly improved capacities for chondrogenesis and articular cartilage repair. We believe that this work demonstrates that a multifunctional nanoparticle-based drug delivery system could be beneficial for stem cell therapy. Our results present an opportunity to reverse the symptoms and pathophysiology of OA. Clinical Relevance: The intracellular delivery of KGN to produce BMSCs with enhanced chondrogenic potential may offer a new approach for the treatment of OA.

Background The aim of the present study was to compare the outcomes of patients who underwent different sequences of ipsilateral total hip arthroplasty (THA) and total knee arthroplasty (TKA). Methods We retrospectively identified 47 patients who underwent TKA followed by ipsilateral THA (THA-TKA) and 36 patients who received THA subsequent to ipsilateral TKA (TKA-THA) for rheumatoid arthritis or osteoarthritis between January 2008 and April 2014. Twenty-eight patients were selected for each group after case-control matching with preoperative demographics and protheses of THA. Clinical scores, radiographic results, complication rates, and survivorship were compared. The median duration of follow-up was 110 (range 80–149) months. Results Both groups showed significant improvement in Harris Hip Scores, Knee Society Score, and Short Form-12 at the last follow-up compared to baseline (p p = .939 and .187). Conclusions Patients who underwent ipsilateral THA and TKA with different sequences achieved similar favorable outcomes. Total joint arthroplasty can be performed safely with excellent outcomes in patients with a history of prior ipsilateral THA or TKA. Trial registration The trial was registered in the Chinese Clinical Trial Registry (ChiCTR2000035147) dated 2 August 2020.

Background To determine whether multiple drilling is effective in postponing the need for total hip arthroplasty (THA) in early-stage nontraumatic osteonecrosis of the femoral head (ONFH). Methods We identified 514 patients who were diagnosed with early-stage ONFH between January 2008 and December 2018. One hundred ninety-six patients underwent multiple drilling, and 318 patients had a natural course of progression. One hundred fifty-nine patients were selected for each group after case-control matching for preoperative demographics and modified Ficat and Arlet stage. The rates of THA conversion were compared. We also performed Cox regression to identify risk factors associated with THA conversion in patients who underwent multiple drilling. Results Kaplan-Meier survivorship with an endpoint of THA for nontraumatic reasons were not significantly different between the multiple drilling group (75.6, 95% confidence interval 67.8–83.4%) and the natural course group (72.2, 95% confidence interval 64.8–79.6%) at 5 years (log-rank, P = .191). In the Cox regression model, a larger extent of necrotic lesion, bone marrow edema (BME), and higher postoperative work intensity significantly increased the risk of THA conversion (P P Conclusions Multiple drilling is not effective in reducing the rate of THA conversion in early-stage nontraumatic ONFH. The risk of conversion to THA after multiple drilling is increased by a larger extent of necrotic lesion, presence of BME, and higher postoperative work intensity in patients with early-stage ONFH. Trial registration The trial was registered in the Chinese Clinical Trial Registry (ChiCTR2000035180) dated 2 August 2020.

Background Previous studies have demonstrated the efficacy of duloxetine in reducing postoperative pain and opioid consumption. However, the effect of duloxetine on total hip arthroplasty (THA) remains unclear. The objective of this study was to assess the efficacy of oral duloxetine in THA. Methods We enrolled 96 patients in this randomized controlled trial. These patients were randomized (1,1) to either the duloxetine group or the placebo group and received daily doses of 60 mg duloxetine or placebo, respectively, from 2 d pre-operation to 14 d after surgery. The primary outcome was pain severity upon movement measured by a visual analogue scale (VAS). The secondary outcomes included VAS scores for resting pain, morphine consumption, Harris Hip Score, patient satisfaction at discharge, length of postoperative hospital stay, and adverse events. Results Patients in the duloxetine group had significantly lower pain severity scores upon movement within 3 postoperative weeks (p Conclusions Although it did not result in a clinically meaning reduction in pain after total hip arthroplasty, perioperative administration of 60 mg of duloxetine daily significantly alleviated pain in the postoperative 3 weeks and morphine requirements during the postoperative 48 h. Therefore, duloxetine still shows promise in optimizing the multimodal pain-management protocols in total hip arthroplasty. Trial registration Chinese Clinical Trial Registry, ChiCTR2000033606, 06/06/2020.

Osteoarthritis (OA) is the most common disabling joint disease throughout the world and its therapeutic effect is still not satisfactory in clinic nowadays. Recent studies showed that the exosomes derived from several types of mesenchymal stem cells (MSCs) could maintain chondrocyte homeostasis and ameliorate the pathological severity of OA in animal models, indicating that MSCs-derived exosomes could be a novel promising strategy for treating OA. In this study, we investigated the role and underlying mechanisms of infrapatellar fat pad (IPFP) MSCs-derived exosomes (MSCIPFP-Exos) on OA in vitro and in vivo. Our data revealed that MSCIPFP could produce amounts of MSCIPFP-Exos, which exhibited the typical morphological features of exosomes. The MSCIPFP-Exos ameliorated the OA severity in vivo and inhibited cell apoptosis, enhanced matrix synthesis and reduced the expression of catabolic factor in vitro. Moreover, MSCIPFP-Exos could significantly enhance autophagy level in chondrocytes partially via mTOR inhibition. Exosomal RNA-seq showed that the level of miR-100-5p that could bind to the 3'-untranslated region (3'UTR) of mTOR was the highest among microRNAs. MSCIPFP-Exos decreased the luciferase activity of mTOR 3'UTR, while inhibition of miR-100-5p could reverse the MSCIPFP-Exos-decreased mTOR signaling pathway. Intra-articular injection of antagomir-miR-100-5p dramatically attenuated MSCIPFP-Exos-mediated protective effect on articular cartilage in vivo. In brief, MSCIPFP-derived exosomes protect articular cartilage from damage and ameliorate gait abnormality in OA mice by maintaining cartilage homeostasis, the mechanism of which may be related to miR100-5p-regulated inhibition of mTOR-autophagy pathway. As it is relatively feasible to obtain human IPFP from OA patients by arthroscopic operation in clinic, MSCIPFP-derived exosomes may be a potential therapy for OA in the future.

One-step clinical therapies of articular cartilage defects remains a challenge. In this study, a strategy was proposed to utilize type II collagen (Col-II) gels with autologous bone marrow-derived cells (BMDCs) embedded to repair full-thickness chondral defects. Its feasibility and efficacy were further assessed in a minipig model. An 8-mm full-thickness chondral defect was created on the femoral trochlea of two knees in Guizhou minipigs. One knee received Col-II gels with BMDCs implantation versus the untreated one as control. After 1, 3, and 6 months operation, the animals were sacrificed, and the repair outcomes of chondral defects were evaluated using Magnetic Resonance Imaging (MRI), macro- and microscopic observation, and histological analysis. The treatment group showed significantly better repair outcomes of chondral defects than that in the control group at each time point (P < 0.01). Furthermore, the image showed that the repaired tissue in the treatment group was more similar to the surrounding healthy cartilage tissue. Based on the hyaline-like tissue regenerated ability, this one-step strategy provides a promising therapeutic potential for clinical application.

Background Total hip arthroplasty (THA) is technically challenging in patients with high dislocation of the hip secondary to suppurative arthritis. The technical difficulty is attributable to the complex hip anatomy and the potential risk of recurrent infection in these patients. This study investigated the midterm results of THA in patients with Crowe type III and IV high dislocation of the hip secondary to suppurative arthritis. Methods This study retrospectively reviewed 45 patients (45 hips) who underwent cementless THA with a mean quiescent infection period of 34.2 years. This study included 23 men and 22 women (mean age, 45.9 years) at the time of operation. The mean follow-up was 6.4 years. Clinical and radiographic outcomes and complications were evaluated. Results The mean Harris hip score significantly improved from 48.1 to 87.6. The modified Merle d'Aubigne-Postel, Western Ontario and McMaster Universities Arthritis Index, low back pain visual analog scale, and the 12-item short-form health survey scores also improved significantly. The mean limb length discrepancy was reduced from 38.9 mm to 6.4 mm. Postoperative dislocation occurred in 2, temporary sciatic nerve paralysis in 3, and intraoperative fracture in 2 patients. Infection and femoral stem loosening necessitated hip revision surgery in 1 patient each. Conclusion THA could provide good joint function and significantly improve quality of life at the time of midterm follow-up in patients undergoing high hip dislocation secondary to suppurative arthritis. However, a relatively high incidence of complications occurred which can be treated.

Background Total hip arthroplasty (THA) altered the mechanical axis and loading distribution of the lower extremity. The effect of a prior THA on clinical outcomes of a subsequent ipsilateral total knee arthroplasty (TKA) remains unknown. Methods We reviewed 83 patients who underwent ipsilateral THA and TKA for rheumatoid arthritis or osteoarthritis between January 2008 and April 2014. Forty-seven patients were classified as TKA followed by ipsilateral THA (THA-TKA group) and 36 as THA subsequent to ipsilateral TKA (TKA-THA group). Twenty-eight patients (30 hips and knees) were selected for each group after the propensity score was matched with preoperative demographics and hip-knee-ankle angle (HKA). Clinical measurements, radiographic evaluations, and complication data were compared between 2 groups. Results Both groups had a significant improvement in modified Harris Hip Scores (HHS), Knee Society Score (KSS), and Short Form-12 at final follow-up compared to baseline (p p > .05). Meanwhile, there was no significant difference in postoperative radiographic axial alignment and implant survivorship (90.0% vs 96.7%, p = .305). The rate of complication was also similar in both groups. Conclusions A prior THA does not appear to influence clinical outcome of a subsequent ipsilateral TKA. Patients with different sequence of ipsilateral THA and TKA have similar mid-long term clinical outcomes and implant survivorship. Trial registration: The trial was registered in the Chinese Clinical Trial Registry (ChiCTR2000035147) dated 2rd August 2020.

Abundant literature confirms that intravenous (IV) and intra-articular (IA) administration of tranexamic acid (TXA) reduces blood loss in total knee arthroplasty (TKA). Oral formulations of TXA exhibit profound cost-saving benefits. However, comparisons of the clinical efficacy among three different modalities of TXA administration have not been previously investigated in the setting of TKA with no closed suction drain and tourniquet. A total of 180 patients undergoing TKA were randomized to receive 2-g oral TXA 2 hours preoperatively, 20-mg/kg IV TXA 5 minutes prior to incision, or 2-g IA TXA. The primary outcome was 72-hour blood loss. Secondary outcomes were reductions in hemoglobin, the rate of transfusions, and adverse events. No significant differences were identified with regard to the mean 72-hour blood loss among the three groups (1003 mL in oral group, 1108 mL in IV group, and 1059 mL in IA group, respectively). Similarly, hemoglobin reduction was equivalent among the groups. Only one patient in IV group exhibited deep venous thrombosis. No difference was identified regarding transfusion rates. Oral TXA results in similar blood loss in TKA, with a profound cost-saving benefit, compared with the IA and IV formulations.

Background The majority of the existing evidence showing an association between diabetes and impaired fracture healing comes from basic scientific research. This systematic review and meta-analysis aimed to summarize the current clinical literature that investigates fracture healing in patients with diabetes. Methods The outcome of interest was impaired fracture healing including non-union, delayed union and malunion. Studies that compared fracture healing outcomes between patients with and without diabetes were included in this study. Subgroup analyses regarding different fracture sites, types of fracture and classifications of diabetes were performed. Results A total of 14 studies involving 695 patients with diabetes and 4937 controls fulfilled the inclusion criteria. Diabetes was associated with an increased risk of impaired fracture healing (odds ratio (OR): 2.11, 95% confidence interval (CI) 1.33-3.37, P = 0.002). Subgroup analyses showed that diabetes was associated with a significantly higher incidence of impaired fracture healing in lower extremity fractures (OR 2.63, 95% CI 1.30-5.30, P = 0.007), short bone fractures (OR 2.64, 95% CI 1.35-5.20, P = 0.005), long bone fractures (OR 2.13, 95% CI 1.23-3.70, P = 0.007) and osteoporosis-unrelated fractures (OR 2.39, 95% CI 1.19-4.80, P = 0.01). Both insulin-dependent diabetes (OR 4.04, 95% CI 1.05-15.56, P = 0.04) and non-insulin-dependent diabetes (OR 5.83, 95% CI 1.73-19.58, P = 0.004) were associated with significantly higher risks of impaired fracture healing. Conclusions Patients with diabetes have an increased risk of impaired fracture healing when compared to patients without diabetes. Fracture healing in the lower extremities, short bones and osteoporosis-unrelated fractures is affected more severely by diabetes.

The reductions of perioperative blood loss and inflammatory response are important in total knee arthroplasty. Tranexamic acid reduced blood loss and the inflammatory response in several studies. However, the effect of epinephrine administration plus tranexamic acid has not been intensively investigated, to our knowledge. In this study, we evaluated whether the combined administration of low-dose epinephrine plus tranexamic acid reduced perioperative blood loss or inflammatory response further compared with tranexamic acid alone.This randomized placebo-controlled trial consisted of 179 consecutive patients who underwent primary total knee arthroplasty. Patients were randomized into 3 interventions: Group IV received intravenous low-dose epinephrine plus tranexamic acid, Group TP received topical diluted epinephrine plus tranexamic acid, and Group CT received tranexamic acid alone. The primary outcome was perioperative blood loss on postoperative day 1. Secondary outcomes included perioperative blood loss on postoperative day 3, coagulation and fibrinolysis parameters (measured by thromboelastography), inflammatory cytokine levels, transfusion values (rate and volume), thromboembolic complications, length of hospital stay, wound score, range of motion, and Hospital for Special Surgery (HSS) score.The mean calculated total blood loss (and standard deviation) in Group IV was 348.1 ± 158.2 mL on postoperative day 1 and 458.0 ± 183.4 mL on postoperative day 3, which were significantly reduced (p0.05) compared with Group TP at 420.5 ± 188.4 mL on postoperative day 1 and 531.1 ± 231.4 mL on postoperative day 3 and Group CT at 520.4 ± 228.4 mL on postoperative day 1 and 633.7 ± 237.3 mL on postoperative day 3. Intravenous low-dose epinephrine exhibited a net anti-inflammatory activity in total knee arthroplasty and did not induce an obvious hypercoagulable status. Transfusion values were significantly reduced (p0.05) in Group IV, but no significant differences were observed in the incidence of thromboembolic complications, wound score, range of motion, and HSS score among the 3 groups (p0.05).The combined administration of low-dose epinephrine and tranexamic acid demonstrated an increased effect in reducing perioperative blood loss and the inflammatory response compared with tranexamic acid alone, with no apparent increased incidence of thromboembolic and other complications.Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Cell senescence is a chronic process associated with age-related degenerative diseases such as osteoarthritis (OA). Senescent cells (SnCs) accumulate in the articular cartilage and synovium, leading to OA pathologies. The accumulation of SnCs in the cartilage results in a senescence-associated secretory phenotype (SASP) and age-related inflammation and dysfunction. Selective removal of SnCs by senolytic agent as a therapeutic strategy has been developed recently. In this study, we examined the ability of the senolytic drug ABT263 (navitoclax) to clear SnCs and further evaluated the therapeutic effect of ABT263 on post-traumatic OA. Monolayer and 3D pellet cultured osteoarthritic chondrocytes were used to evaluate the effect of ABT263 in vitro and a DMM rat model was established for in vivo experiments. We found that ABT263 reduced the expression of inflammatory cytokines and promoted cartilage matrix aggregation in OA chondrocyte pellet culture by inducing SnC apoptosis. Moreover, OA pathological changes in the cartilage and subchondral bone in post-traumatic OA rat were alleviated by ABT263 intra-articular injection. These results demonstrated that ABT263 not only improves inflammatory microenvironment but also promotes cartilage phenotype maintenance in vitro. Furthermore, ABT263 might play a protective role against post-traumatic OA development. Therefore, strategies targeting SnC elimination might be promising for the clinical therapy of OA.

Tranexamic acid (TXA) reduces surgical blood loss and alleviates inflammatory response in total hip arthroplasty. However, studies have not identified an optimal regimen. The objective of this study was to identify the most effective regimen of multiple-dose oral TXA in achieving maximum reduction of blood loss and inflammatory response based on pharmacokinetic recommendations. We prospectively studied four multiple-dose regimens (60 patients each) with control group (group A: matching placebo). The four multiple-dose regimens included: 2-g oral TXA 2 hours pre-operatively followed by 1-g oral TXA 3 hours post-operatively (group B), 2-g oral TXA followed by 1-g oral TXA 3 and 7 hours post-operatively (group C), 2-g oral TXA followed by 1-g oral TXA 3, 7 and 11 hours post-operatively (group D) and 2-g oral TXA followed by 1-g oral TXA 3, 7, 11 and 15 hours post-operatively (group E). The primary endpoint was estimated blood loss on post-operative day (POD) 3. Secondary endpoints were thromboelastographic parameters, inflammatory components, function recovery and adverse events. Groups D and E had significantly less blood loss on POD 3, with no significant difference between the two groups. Group E had the most prolonged haemostatic effect, and all thromboelastographic parameters remained within normal ranges. Group E had the lowest levels of inflammatory cytokines and the greatest range of motion. No thromboembolic complications were observed. The post-operative four-dose regimen brings about maximum efficacy in reducing blood loss, alleviating inflammatory response and improving analgaesia and immediate recovery.

Objective To evaluate whether closed suction drainage (CSD) is associated with early recovery of knee function in patients undergoing total knee arthroplasty (TKA). Methods Between January 2015 and September 2015, 80 consecutive patients were prospectively randomized into two groups: a CSD group (40 cases; average age, 66.9 ± 8.6 years; male, 8; female, 32) and a non-CSD group (40 cases; average age, 66.8 ± 10.1 years; male, 9; female, 31). Local inflammation outcomes (assessed by a visual analog scale [VAS], swelling and skin temperature), calculated total blood loss (CBL), hidden blood loss (HBL), blood transfusion requirements and hemoglobin concentrations were recorded. Hospital for Special Surgery (HSS) knee scores, range of motion (ROM), limb swelling, tension vesicles, ecchymosis, time to regaining straight leg raising and duration of hospital stay were documented. All surgeries were performed by the same surgeon and followed up for 3 months. Results The peri-wound skin temperature and knee VAS pain scores were lower in the non-CSD group. Patients in the non-CSD group had significantly better knee ROM (P = 0.028). The time to regaining active straight leg raising was significantly shorter in the non-CSD groupN than in the CSD group (P = 0.014). In addition, patients in the non-CSD group had a shorter length of hospital stay (P = 0.004) than those in the CSD group, indicating earlier recovery of knee function. HBL was significantly less in the CSD group than the non-CSD group (P = 0.006) on postoperative day (POD) 5. However, CBL did not differ significantly between the two groups on POD5. There were no significant differences between two groups in all other assessed variables. Conclusion In this randomized study, primary TKA without CSD was associated with faster recovery related to less local inflammation and better early knee function. Furthermore, use of a drain had no significant advantage with respect to other outcome measures and may have increased costs. Based on these data, CSD after primary TKA is not routinely indicated.

Aims The aim of this study was to identify the most effective regimen of multiple doses of oral tranexamic acid (TXA) in achieving maximum reduction of blood loss in total knee arthroplasty (TKA). Patients and Methods In this randomized controlled trial, 200 patients were randomized to receive a single dose of 2.0 g of TXA orally two hours preoperatively (group A), a single dose of TXA followed by 1.0 g orally three hours postoperatively (group B), a single dose of TXA followed by 1.0 g three and nine hours postoperatively (group C), or a single dose of TXA followed by 1.0 g orally three, nine, and 15 hours postoperatively (group D). All patients followed a routine enhanced-recovery protocol. The primary outcome measure was the total blood loss. Secondary outcome measures were hidden blood loss (HBL), reduction in the level of haemoglobin, the rate of transfusion and adverse events. Results Groups C (661.1 ml, sd 262.4) and D (597.7 ml, sd 219.6) had significantly lower mean total blood loss compared with groups A and B. The mean HBL was significantly lower in groups B (699.2 ml), C (533.1 ml) and D (469.9 ml) than in group A (p = 0.006, p Conclusion The addition of two or three postoperative doses of TXA to one preoperative dose produced a significant reduction in blood loss. The two-dose postoperative regimen is the least necessary regimen for clinical efficacy in primary unilateral TKA. The three-dose regimen produced maximum reduction of blood loss. Cite this article: Bone Joint J 2018;100-B:1025–32.

Essentials Perioperative blood loss and inflammatory response can significantly affect recovery after surgery. We studied the effects of multiple-dose oral tranexamic acid on blood loss and inflammatory response. A postoperative four-dose regimen brought about maximum reduction in postoperative blood loss. A postoperative four-dose regimen reduced inflammatory response and promoted early rehabilitation. SUMMARY: Background Tranexamic acid (TXA) can reduce blood loss and the inflammatory response at multiple doses in total knee arthroplasty patients. However, the optimal regimen has not been determined. Objectives To identify the most effective regimen for achieving maximum reductions in blood loss and the inflammatory response. Patients/Methods Two hundred and seventy-five patients were randomized to receive a placebo (group A), a single 2-g oral dose of TXA 2 h preoperatively followed by 1 g of oral TXA 3 h postoperatively (group B), a single dose followed by 1 g of oral TXA 3 h and 7 h postoperatively (group C), a single dose followed by 1 g of oral TXA 3 h, 7 h and 11 h postoperatively (group D), or a single dose followed by 1 g of oral TXA 3 h, 7 h, 11 h and 15 h postoperatively (group E). The primary outcome was total blood loss on postoperative day (POD) 3. Secondary outcomes included a decrease in the hemoglobin level, coagulation parameters, inflammatory marker levels, and thromboembolic complications. Results Groups D and E had significantly lower blood loss and smaller decreases in hemoglobin level than groups A, B, and C, with no significant difference on POD 3 between groups D and E. Significantly enhanced coagulation was identified for the four multiple-dose regimens; however, all thromboelastographic parameters remained within normal ranges. Group E had the lowest inflammatory marker levels and pain, and the greatest range of motion. No thromboembolic complications were identified. Conclusion The four-dose regimen yielded the maximum reductions in blood loss and inflammatory response, improved analgesia, and promoted early rehabilitation. Further studies are required to ensure that these findings are reproducible.

Objective To assess the difference between drainage and non-drainage after total hip arthroplasty (THA) in Chinese subjects by evaluating post-operative complications and joint function. Methods One hundred and sixty-eight patients undergoing THA were randomly allocated into drainage (83 patients) and non-drainage groups (85 patients). All surgeries were performed by one surgical team using the same pre-, intra-, and postoperative techniques. Measured items included: hemoglobin (Hb), superficial and deep wound infection, volume of blood transfusion, wound hematoma thickness, range of motion (ROM) of the hip, wound healing time, ecchymosis and tension vesicles around the wound. Results Early after THA, the Hb decreased significantly in the drainage group. There was no significant difference between non-drainage and drainage groups in need for or volume of blood transfusions (9.6% vs 8.2%, P = 0.100; 3.8 units vs 2.9 units, P = 0.089, respectively). In the non-drainage group, the incidence of superficial infection, ecchymosis and tension vesicles was significantly higher than in the drainage group (10.6% vs 2.4%, P = 0.031; 12.9% vs 3.6%, P = 0.026; 16.5% vs 4.8%, P = 0.013, respectively). In addition, the non-drainage group had a greater volume of hematomas (P = 0.000). Patients in the non-drainage group had smaller ROMs early after surgery but the final ROMs did not differ significantly between groups. No deep infection occurred in either group. Conclusion Non-drainage may reduce postoperative blood loss but has no benefits regarding blood transfusion or deep infection. It may cause more post-operative complications because of restriction of early postoperative exercise by pain and swelling. Therefore we suggest routine use of drainage after THA.

Accumulating evidences have indicated that the functional -94 ins/del ATTG polymorphism in the promoter region of human nuclear factor-kappa B1 (NFKB1) gene may be associated with cancer risk. However, some studies yielded conflicting results. To clarify precise association, we performed a comprehensive meta-analysis of 42 case-control studies involving 43,000 subjects (18,222 cases and 24,778 controls). The overall results suggested that the -94 ins/del ATTG polymorphism had a decreased risk for cancer, reaching significant levels in five genetic models (dominant model: OR = 0.86, 95% CI = 0.79–0.95, P = 0.002; recessive model: OR = 0.84, 95% CI = 0.74–0.94, P = 0.003; homozygous model: OR = 0.77, 95% CI = 0.66–0.90, P = 0.001; heterozygous model: OR = 0.90, 95% CI = 0.83–0.98, P = 0.011; allelic model: OR = 0.89, 95% CI = 0.83–0.96, P = 0.002). Furthermore, the -94 ins/del ATTG polymorphism could confer a decreased or increased risk for cancer development among Asians and Caucasians, respectively. Additionally, the stratification analysis revealed a significant association between the variant and decreased risk of oral, ovarian and nasopharyngeal cancer in Asians. After we adjusted p values using the Benjamini-Hochberg false discovery rate method to account for multiple comparisons, these associations remained.

The cause of hip osteoarthritis (OA) remains unclear, morphologic abnormality of hip was thought to be a contributing factor to hip OA. The hypothesis was that there were subtle anatomical morphology differences of the hip between normal and OA subjects; the objective of this study was to explore these anatomical differences which are predisposing to hip OA based on CT 3D reconstruction. Ninety-three normal subjects (186 hips) and 66 mild-to-moderate hip OA subjects (132 hips) were recruited in this study. Three parameters of the head-neck relationship were assessed: translation, rotation and concavity. Translation was the potential translational movements of femoral head related to the neck’s axis. Rotation was described by the physeal scar to evaluate the rotation tendency of femoral head related to the neck at the head-neck junction. Concavity was used to assess the sphericity of the head as it joins the neck. The femoral neck anteversion angle and some parameters of the acetabulum: anteversion, inclination and CE angle were measured too. By comparison, it was found that OA subjects had less femoral head sphericity, head-neck junction concavity, acetabular and femoral neck anteversion angle; but greater acetabular coverage. These characteristics increased the risk of hip OA in OA subjects.