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The current study aimed to determine the safety profile of intra-articular-injected allogeneic adipose-derived mesenchymal stem cells (ADSCs) GXCPC1 in subjects with knee osteoarthritis (OA) and its preliminary efficacy outcome. The 3 + 3 phase I study was designed with two dose-escalation cohorts: low dose (6.7 × 10 6 GXCPC1, N = 5) and high dose (4 × 10 7 GXCPC1, N = 6). The primary endpoint was safety, which was evaluated by recording adverse events throughout the trial; the secondary endpoints included total, pain, stiffness, and function subscales of the Western Ontario and McMaster Universities Arthritis Index (WOMAC), Visual Analogue Scale (VAS) for pain, and 12-Item Short Form (SF-12) health survey questionnaire. The GXCPC1 treatment was found to be safe after 1 year of follow-up with no treatment-related severe adverse events observed. When compared to baseline, subjects in both the low- and high-dose cohorts demonstrated improving trends in pain and knee function after receiving GXCPC1 treatment. Generally, the net change in pain (95% confidence interval (CI) = −7.773 to −2.561t at 12 weeks compared to baseline) and knee function (95% CI = −24.297 to −10.036t at 12 weeks compared to baseline) was better in subjects receiving high-dose GXCPC1. Although this study included a limited number of subjects without a placebo arm, it showed that the intra-articular injection of ADSCs was safe and well-tolerated in subjects with therapeutic alternatives to treat knee OA. However, a larger scale study with an appropriate control would be necessary for clinical efficacy in the following study.

Abstract Simultaneous bilateral total knee arthroplasty (TKA) might be associated with higher postoperative morbidity and mortality rates compared with staged bilateral TKA. However, risk factors for surgical complications and reoperations following simultaneous bilateral TKA remain elusive. We conducted this retrospective, single-surgeon case series from 2010 through 2019. A total of 1561 patients who underwent simultaneous bilateral TKA procedures were included. The outcome domains included 30-day and 90-day readmission events for medical or surgical complications and 1-year reoperation events. We performed logistic regression analysis and backward stepwise selection to identify possible risk factors, including age, sex, body mass index, diabetes mellitus (DM), rheumatoid arthritis, American Society of Anesthesiologist (ASA) classification, Charlson Comorbidity Index (CCI), receiving venous thromboembolism (VTE) prophylaxis, or blood transfusion. The overall 30-day, 90-day readmission, and 1-year reoperation rates were 2.11%, 2.88%, and 1.41%, respectively. Higher CCI score (CCI = 4+) was a risk factor for 90-day readmission (aOR: 2.783; 95% CI 0.621–12.465), 90 day readmission for surgical complications (aOR: 10.779; 95% CI 1.444–80.458), and 1 year reoperation (aOR: 4.890; 95% CI 0.846–28.260). Other risk factors included older age, higher ASA level, DM, and receiving VTE prophylaxis. In conclusion, high CCI scores were associated with increased risks of surgical complications and reoperations following simultaneous bilateral TKA procedures.

Abstract Venous thromboembolism (VTE) prophylaxis has been suggested for patients who underwent total join arthroplasty (TJA). However, the morbidity of surgical site complications (SSC) and periprosthetic joint infection (PJI) has not been well evaluated. We aimed to evaluate the impact of VTE prophylaxis on the risk of early postoperative SSC and PJI in a Taiwanese population. We retrospectively reviewed 7511 patients who underwent primary TJA performed by a single surgeon from 2010 through 2019. We evaluated the rates of SSC and PJI in the early postoperative period (30-day, 90-day) as well as 1-year reoperations. Multivariate regression analysis was used to identify possible risk factors associated with SSC and PJI, including age, sex, WHO classification of weight status, smoking, diabetes mellitus (DM), rheumatoid arthritis(RA), Charlson comorbidity index (CCI), history of VTE, presence of varicose veins, total knee or hip arthroplasty procedure, unilateral or bilateral procedure, or receiving VTE prophylaxis or blood transfusion. The overall 90-day rates of SSC and PJI were 1.1% (N = 80) and 0.2% (N = 16). VTE prophylaxis was a risk factor for 90-day readmission for SSC (aOR: 1.753, 95% CI 1.081–2.842), 90-day readmission for PJI (aOR: 3.267, 95% CI 1.026–10.402) and all 90-day PJI events (aOR: 3.222, 95% CI 1.200–8.656). Other risk factors included DM, underweight, obesity, bilateral TJA procedure, younger age, male sex and RA. Pharmacological thromboprophylaxis appears to be a modifiable risk factor for SSC and PJI in the early postoperative period. The increased infection risk should be carefully weighed in patients who received pharmacological VTE prophylaxis.

Abstract Background The choice of femur stems during the hip arthroplasty procedures for patients with treatment failure of intertrochanteric fractures (ITF) remains controversial. We aimed to compare the surgical complication and reoperation rates between cementless primary and revision stems in the early (≤3 months) and late (> 3 months) fixation failures of ITF. Methods This was a retrospective, cohort study conducted in a single, tertiary referral hospital of Taipei, Taiwan. We included hip arthroplasty procedures for failed ITF using cementless primary or revision stems. There were 40 and 35 patients who had early and late fixation failure of ITF, respectively. The patient demographics, time to fixation failure, surgical complications and medical complications were recorded for analysis. Results We included 75 patients that underwent hip arthroplasty procedure for failed ITF using cementless primary (n = 38) or revision (n = 37) stems. The mean age was 79.3 years and 56% of the patients were female. In the early fixation failure group, the complication rate was similar between the primary and revision stems (44% vs. 29%, p = 0.343). However, there was a trend toward a higher reoperation rate (31% vs. 8%, p = 0.061) of using the primary stem, compared with the revision stem. In the late fixation failure group, the rate of complication and reoperation was similar between the two stem types. Conclusion For early fixation failures of ITFs, we caution against the use of cementless primary stems due to a trend towards an increased risk of reoperations compared to the use of cementless revision stems. However, in late fixation failures of ITFs, there is a role for cementless primary stems. Level of evidence III, retrospective cohort study.

Abstract Objective To evaluate the safety and efficacy of intra-articular (IA) injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE® for knee osteoarthritis. Methods This was a patient-blind, randomized, active-control trial consisted of 4 arms including hyaluronic acid (HA) control and 3 ELIXCYTE® doses. A total of 64 subjects were screened, and 57 subjects were randomized. The primary endpoints included the changes from baseline to post-treatment visit of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at Week 24 and the incidence of adverse events (AEs) and serious adverse events (SAEs). Results No ELIXCYTE®-related serious adverse events were reported during 96 weeks of follow-up and no suspected unexpected serious adverse reaction (SUSAR) or death was reported. The changes of the primary endpoint, WOMAC pain score at Week 24, showed significant differences in all ELIXCYTE® groups, as well as in HA groups between post-treatment visit and baseline. The ELIXCYTE® groups revealed significant decreases at Week 4 compared to HA group in WOMAC total scores, stiffness scores, functional limitation scores suggested the potential of ELIXCYTE® in earlier onset compared to those from HA. The significant differences of visual analog scale (VAS) pain score and Knee Society Clinical Rating System (KSCRS) functional activities score at Week 48 after ELIXCYTE® administration suggested the potential of ELIXCYTE® in the longer duration of the effectiveness compared to HA group. Conclusions ELIXCYTE® for knee osteoarthritis treatment was effective, safe, and well-tolerated. The efficacy results were showed that ELIXCYTE® conferred the earlier onset of reductions in pain scores and improvements in functional scores than HA group. Trial registration: ClinicalTrials.gov Identifier: NCT02784964. Registered 16 May, 2016—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02784964

Abstract Background The administration of an intra-articular injection (IAI) of tranexamic acid (TXA) has been demonstrated to be effective in reducing both blood loss and transfusion rate during total knee arthroplasty (TKA); however, few studies have reported the efficiency of a peri-articular injection (PAI) of TXA. We studied the efficiency of a PAI of TXA in reducing blood loss during TKA. Methods Fifty patients undergoing primary simultaneous bilateral TKA were enrolled in this retrospective study. The right knee received a PAI of 1 g of TXA (Group I), and the left knee received an IAI of 1 g of TXA (Group II). The clinical outcome measures were a change in blood loss from Hemovac drains and surgical time. Results The decrease in blood loss from the Hemovac was significantly lower in Group I (460.1 ± 36.79 vs. 576.0 ± 34.01, P

Abstract Background The aims of this meta-analysis were to: (1) validate the outcome of modern dual mobility (DM) designs in patients who had undergone primary and revision total hip arthroplasty (THA) procedures and (2) to identify factors that affect the outcome. Methods We searched for studies that assessed the outcome of modern DM-THA in primary and revision procedures that were conducted between January, 2000 to August, 2020 on PubMed, MEDLINE, Cochrane Reviews and Embase. The pooled incidence of the most common failure modes and patient reported outcomes were evaluated in patients who have received: (1) primary THA, (2) revision THA for all causes or (3) for recurrent dislocation. A meta-regression analysis was performed for each parameter to determine the association with the outcome. The study design of each study was assessed for potential bias and flaws by using the quality assessment tool for case series studies. Results A total of 119 studies (N= 30016 DM-THAs) were included for analysis. The mean follow-up duration was 47.3 months. The overall implant failure rate was 4.2% (primary: 2.3%, revision for all causes: 5.5%, recurrent dislocation: 6.0%). The most common failure modes were aseptic loosening (primary: 0.9%, revision for all causes: 2.2%, recurrent dislocation: 2.4%), septic loosening (primary:0.8%, revision for all causes: 2.3%, recurrent dislocation: 2.5%), extra-articular dislocation (primary:0.6%, revision for all causes:1.3%, recurrent dislocation:2.5%), intra-prosthetic dislocation (primary:0.8%, revision for all causes:1.0%, recurrent dislocation:1.6%) and periprosthetic fracture (primary:0.9%, revision for all causes:0.9%, recurrent dislocation:1.3%). The multi-regression analysis identified younger age (β=-0.04, 95% CI -0.07 – -0.02) and female patients (β=3.34, 95% CI 0.91–5.78) were correlated with higher implant failure rate. Age, gender, posterolateral approach and body mass index (BMI) were not risk factors for extra-articular or intra-prosthetic dislocation in this cohort. The overall Harris hip score and Merle d’Aubigné score were 84.87 and 16.36, respectively. Level of evidence of this meta-analysis was IV. Conclusion Modern dual-mobility designs provide satisfactory mid-term implant survival and clinical performance. Younger age and female patients might impact the outcome after DM-THA. Future research directions should focus on, (1) long-term outcome of modern dual-mobility design, including specific concerns such as intra-prosthetic dislocation and elevated metal ion, and (2) cost-effectiveness analysis of dual-mobility implant as an alternative to conventional THA for patients who are at high risk of dislocation.

Abstract Multimodal pain management protocol effectively relieves pain following simultaneous bilateral total knee arthroplasty (SBTKA) but is associated with administration of large amounts of opioids in the perioperative period. In this prospective, randomized, assessor-blinded, single-surgeon clinical trial, the goal was to validate the efficacy of an opioid-sparing protocol for SBTKA with a reduced opioid dose, while achieving similar pain relief with few adverse events. Fifty-six patients who had undergone SBTKA were randomly allocated to receive either an opioid-sparing or opioid-based protocol. The primary outcome parameters were visual analogue scale (VAS) scores at rest, with movement, and cumulative morphine dose, through time. Secondary outcome parameters included drug-related adverse events and range of motion with continuous passive motion device, through time. In the opioid-sparing group, a lower VAS score with movement at postoperative 24 and 72 h was observed compared with the opioid-based group, but the difference did not reach the minimal clinically importance difference. A reduced cumulative morphine dose was noted in the opioid-sparing group at postoperative 24, 48 and 72 h. In conclusion, the opioid-sparing protocol may be used as an alternative modality for pain management following SBTKA. Similar pain relief effects may be achieved utilizing a reduced cumulative opioid dose, with few opioid related adverse events.

Abstract Background Elderly patients with femoral neck fractures are at a higher risk of dislocation after hip arthroplasty procedures. In comparison with total hip arthroplasty (THA), bipolar hemiarthroplasty (HA) and dual-mobility total hip arthroplasty (DM-THA) can be an effective alternative treatment which increases the effective head size and overall stability of the prosthesis. We aim to review the current evidence on the outcome after DM-THA and HA for femoral neck fractures in the elderly. Methods We performed a comprehensive review of literatures on PubMed, Embase, Web of Science, and the Cochrane Library for randomized controlled trials and comparative interventional studies. Of the 936 studies identified, 8 met the inclusion criteria (541 DM-THA and 603 HA procedures). Two reviewers independently reviewed and graded each study and recorded relevant data including dislocation rate, implant failure rate, reoperation rate, 1-year mortality rate, Harris hip score (HHS), operation time, and intraoperative blood loss. Results DM-THA was associated with a lower dislocation rate (OR 3.599; 95% CI 1.954 to 6.630), a lower reoperation rate (OR 2.056; 95% CI 1.211 to 3.490), an increased operation time (SMD − 0.561; 95% CI − 0.795 to − 0.326) and more intraoperative blood loss (SMD − 0.778; 95% CI − 1.238 to − 0.319), compared with the HA group. Moreover, the multivariate regression analysis revealed that age, female sex, posterolateral surgical approach, and choice of DM-THA or HA were not associated with dislocation or reoperation. Conclusions Based on the current evidence, the advantages reported for DM-THA over HA with regard to dislocation and reoperation rate in elderly patients with FNF remain inconclusive. High-quality studies on the high-risk patients with cognitive disorder or dementia are necessary to validate the value of DM-THA.

Abstract Background Femoral neck fracture (FNF) is among the commonest fractures affecting the geriatric population. Hemiarthroplasty (HA) is a standard treatment procedure and has been performed by hip surgeons for decades. Recently, primary total hip replacement has proved advantageous for the treatment of such fractures. The aim of this study is to retrospectively review all causes of failure of all patients who underwent HA in our institute and reevaluated whether HA remains a favourable choice of treatment for patients with displaced FNFs. Methods A total of 4516 patients underwent HA at our centre from 1998 to 2017. The HA implants included unipolar and bipolar prostheses. Patients diagnosed with displaced FNF, underwent primary HA initially, required second revision procedures, and followed up for a minimum of 36 months were included in this study. Data were collected and comprehensively analysed. Results In 4516 cases, 99 patients underwent second surgeries. The revision rate was 2.19%. Reasons for failure were acetabular wear (n = 30, 30.3%), femoral stem subsidence (n = 24, 24.2%), periprosthetic fracture (n = 22, 22.2%), infection (n = 16, 16.2%), and recurrent dislocation (n = 7, 7.1%). The mean follow-up period was 78.1 months. The interval between failed HA and revision surgery was 22.8 months. Conclusion HA has a low revision rate and remains a favourable choice of treatment for patients with displaced FNFs. Levels of evidence Level III, Retrospective Cohort Study, Therapeutic Study.

Backgroud/Purpose: Most patients who undergo two-stage exchange arthroplasty surgery for total knee arthroplasty prosthetic joint infection (TKA-PJI) receive a six-week course of systemic antibiotic treatment after the first stage procedure. However, the optimal duration of therapy has not been conclusively determined. Methods: We included 64 patients with periprosthetic knee infection who had undergone two-stage exchange arthroplasty. Between March 2003 and December 2009, 21 patients were given a short-course (less than 1 week) antibiotic treatment, and 43 were given a standard-course (4–6 weeks) treatment during the interim period. We compared length of hospital stay, duration of intravenous and overall systemic antibiotic treatments, and rate of recurrent periprosthetic knee infection between groups. Results: Short-course antibiotic treatment was associated with a shorter hospital stay and a shorter duration of intravenous and systemic antibiotic treatment. Implant survival regarding re-resection arthroplasty and chronic oral antibiotic suppression as primary endpoints was not significant different statistically between two groups (p = 0.317). The 1-year implant survival rates were 91.7% in the short-course group and 89.8% in the standard-course group. The 5-year implant survival rates were 85.2% and 74.0%, respectively. Conclusion: After the first stage of resection arthroplasty for a two-stage exchange arthroplasty, a short course of antibiotic treatment had similar implant survival rates in comparison to the standard 6-week course. With radical debridement combined with an antibiotic-loaded cement spacer along with serial monitoring of the patient, a short course antibiotic treatment may be adequate in patients with TKA-PJI.

Abstract Background Continuous femoral nerve block (cFNB) has been developed to extend the analgesic effect since the efficacy of single-injection femoral nerve block (sFNB) is often limited to approximately 16–24 h. The aim of this meta-analysis was to validate the add-on effect of cFNB in the setting of a multimodal analgesic protocol. Methods We performed a comprehensive literature review on Web of Science, Embase, the Cochrane Library and PubMed. Eight randomized controlled trials (N = 626) that compared the efficacy of cFNB with sFNB were included. The primary outcome domains consist of visual analog scale (VAS) score at postoperative 24 and 48 h. The secondary outcome domains include opioid consumption, length of hospital stay and incidence of nausea. Results Our analysis revealed that cFNB was associated with a lower VAS score at 24 h (SMD: -0.277;95% CI − 0.503 to − 0.05). However, the difference of VAS score did not meet the minimal clinically importance difference for total knee arthroplasty (TKA). VAS score at 48 h was similar between the cFNB and sFNB group. The cFNB group was associated with less amount of opioids consumed at both 24(SMD: -1.056;95% CI − 1.737 to − 0.375) and 48 h(SMD: -1.040;95% CI − 1.790 to − 0.289). Length of hospital stay and incidence of nausea were similar between the two groups. Conclusion In the setting of a multimodal analgesic protocol, patients might benefit from cFNB with regards to a reduced need of opioids in the early postoperative period. However, we did not find a clinically significant difference in pain scores at different time points between the cFNB and sFNB group. Level of evidence I; meta-analysis.

Background: Alignment correction of the lower limb by medial open-wedge high tibial osteotomy (HTO) is an efficient technique, but loss of correction and hardware failure can occur owing to inadequate fixation. A surgical technique using opposite screw insertion was previously applied for salvage of the lateral hinge fracture, but evidence for its utility as a protective strategy was unclear. Methods: Finite element models were reconstructed using artificial bone models, commercial bone plate, and locking screws in the HTO model. The 6.5-mm cancellous or 6.5/8.0-mm pretensioned lag screw was virtually inserted from the opposite cortex to the medial tibial plateau. Testing loads were applied for simulating standing and initial sit-to-stand postures. The axial displacement of the posteromedial tibial plateau, which represents the loss of the posteromedial tibial plateau in clinical observation, and stresses on the bone plate, locking screws, and opposite screws were evaluated. Results: Pretensioned lag screw insertion effectively reduced the loss of posteromedial reduction compared with the HTO model without opposite screw insertion [6.5-mm lag screw, by 50.8% (standing)/56.3% (sit-to-stand); 8.0-mm lag screws, by 51.9% (standing)/57.5% (sit-to-stand); normalised by the performance in the intact model]. The noncompressed opposite cancellous screw slightly reduced the stresses on the bone plate and screws, but did not contribute to the control of reduction loss at the posteromedial tibial plateau. Stresses on screws were lower than those on the corresponding bone plates, so the risk of screw breakage may be low. Conclusion: The present study revealed that pretensioned opposite lag screw insertion is a simple and effective technique to improve the structural stability in medial open-wedge HTO. Further biomechanical and clinical verification will be required to enhance user confidence in this technique. The translational potential of this article: The efficacy and advantages of additional opposite lag screw insertion in medial wedge high tibial osteotomy surgery have been described in this current study by a virtual biomechanical evaluation. Basing on this observation, it would worth further clinical trials for clarification and verification in reality. Keywords: Biomechanics, High tibial osteotomy, Lag screw, Loss of correction, Open-wedge

Angiogenesis plays an important role in the development of bone and bone regeneration to provide the required molecules. Mesenchymal stem cells (MSCs) are pluripotent, self-renewing, and spindle-shaped cells, which can differentiate into multiple lineages such as chondrocytes, osteocytes, and adipocytes. MSCs derived from bone marrow (BMMSCs), adipose tissue (ADMSCs), and Wharton’s jelly (UCMSCs) are popular in the field of tissue regeneration. MSCs have been proposed that can promote bone regeneration by enhancing vascularization. In this study, the angiogenic potential of secretomes of undifferentiated and osteo-differentiated BMMSCs, ADMSCs, and UCMSCs seeded on human decellularized allogeneic bone were compared. Human umbilical vein endothelial cells (HUVECs) were treated with MSC secretomes. Cell growth, cell migration, and angiogenesis of HUVECs were analyzed by MTT, wound healing, and tube formation assays. Angiogenic gene expression levels of MSCs were evaluated using real-time quantitative PCR. Antibody neutralization was performed to validate the candidate target. Our study demonstrates that the angiogenic gene expression profile is tissue-dependent and the angiogenic ability of secretomes is independent of the state of differentiation. We also explore that IL-1b is important for MSC angiogenic potential. Taken together, this study proves that IL-1b in the secretomes plays a vital role in angiogenesis.

Abstract Background Continuous popliteal sciatic nerve block (CPSNB) has been performed in outpatient foot and ankle surgery as a regional anesthesia method to relieve postoperative pain. Its efficacy as well as safety is yet to be established. There are two purposes of this study: (1) to validate the efficacy of CPSNB with regards to better pain relief and reduced analgesics consumption; (2) to assess the safety of CPSNB. Methods We performed a comprehensive literature review on Web of Science, the Cochrane Library, PubMed and Embase and only included randomized controlled trials (RCTs). Five RCTs that compared the efficacy and safety of CPSNB with the single-injection popliteal sciatic nerve block group were included. The primary outcome parameters were visual analog scale (VAS) scores at postoperative 24, 48 and 72 h. The secondary outcome parameters were amount of oral analgesics consumed, overall patient satisfaction and need of admission after surgery. A sensitivity analysis was performed to explore the consistency of the results. Results In comparison with the single-injection group, CPSNB was associated with a lower VAS score at postoperative 24 and 48 h (p

Abstract Background Although internal fixation has been the main treatment option for elderly patients with an undisplaced femoral neck fracture, it is associated with a high reoperation rate. Some surgeons have discussed the use of hemiarthroplasty, but there is limited literature comparing these two treatment modalities. In this study, we compared the perioperative results of hemiarthroplasty with internal fixation for undisplaced femoral neck fractures. Methods We performed a comprehensive review of literatures on PubMed, Web of Science, Embase, and the Cochrane Library for randomized controlled trials and comparative observational studies. Of the 441 studies initially identified, 3 met all inclusion criteria. Two reviewers independently graded study quality and abstracted relevant data including reoperation rate, mortality rate, Harris Hip Score (HHS), length of hospital stay, and operation duration. Results Our results revealed that hemiarthroplasty was associated with a lower reoperation rate than the internal fixation group (OR 4.489; 95% CI 2.030 to 9.927). Mortality rate at postoperative 1 month and 1 year and HHS at postoperative 1 year and 2 years were not different. Length of hospital stay (SMD − 0.800, 95% CI − 1.011 to − 0.589) and operation duration (SMD − 2.497, 95% CI − 2.801 to − 2.193) were shorter in the internal fixation group. Conclusions Compared with the internal fixation group, patients that underwent hemiarthroplasty had a lower reoperation rate and an equivalent overall mortality rate. Our meta-analysis suggests that hemiarthroplasty might be a better treatment choice than internal fixation in treating elderly patients with an undisplaced femoral neck fracture.

Abstract Background Periarticular injection (PAI) is a regional analgesia method performed in total hip arthroplasty (THA) for postoperative pain relief. However, its efficacy and safety is still inconclusive. Therefore, we conducted this meta-analysis to assess the safety of PAI and to determine if PAI provides better pain relief and reduce the consumption of opioids after THA. Methods We searched PubMed, Web of Science, Embase and the Cochrane Library comprehensively. Only randomized control trials were included in our meta-analysis. Eleven studies that compared the efficacy of PAI with the control group were included. The preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines and Jadad score were applied to assess the quality of the included studies. We used the recommendations by the Cochrane Collaboration to reduce bias and to ensure our results were reliable and veritable. Results Our analysis demonstrated that PAI was more effective than the control group with a lower visual analog scale (VAS) score during rest at 24 h (P = 0.003), 48 h (P = 0.002), and VAS score with activity at 24 h (P = 0.04). There was also less amount of opioid consumption (P = 0.01). There were no differences in length of hospital stay (P = 0.526) and postoperative nausea rate (P = 0.153). Conclusion Compared with the control group, PAI showed better pain relief and less amount of opioid consumption after THA. Our meta-analysis suggests that PAI is a safe and effective multimodal analgesia technique that can be used for THA.

In the last few decades, biological reconstruction techniques have improved greatly for treating high-grade osteosarcoma patients. To conserve the limb, and its function the affected tumor-bearing bones have been treated using liquid nitrogen and irradiation processes that enable the removal of entire tumors from the bone, and these treated autografts can be reconstructed for the patients. Here, we focus on the expressions of the growth factor family proteins from the untreated and treated autografts that play a crucial role in bone union, remodeling, and regeneration. In this proteomic study, we identify several important cytoskeletal, transcriptional, and growth factor family proteins that showed substantially low levels in untreated autografts. Interestingly, these protein expressions were elevated after treating the tumor-bearing bones using liquid nitrogen and irradiation. Therefore, from our preliminary findings, we chose to determine the expressions of BMP2, TGF-Beta, and FGFR proteins by the target proteomics approach. Using a newly recruited validation set, we successfully validate the expressions of the selected proteins. Furthermore, the increased growth factor protein expression after treatment with liquid nitrogen may contribute to bone regeneration healing, assist in faster recovery, and reduce local recurrence and metastatic spread in high-grade sarcoma patients.

Background/purpose: Total knee arthroplasty (TKA) improves the patient's quality of life by relieving pain, correcting the deformity, and helping the patient resume normal activities. However, post-TKA prosthetic joint infection leads to implant failure, is difficult to treat, and causes a significant burden both economically and health-wise. Therefore, an understanding of the current trends in this infection and microbiology data is essential for preventing and treating it. Methods: A retrospective study was conducted on 10,768 patients who underwent primary TKA at Taipei Veterans General Hospital, Taiwan, from 2002 to 2014. The incidence of post-TKA prosthetic joint infection in different time periods was investigated, and microbiological results in early- (

Osteosarcoma over distal fibula is a rare disease. Wide resection of a malignant tumor of the distal fibula may lead to severe lateral ankle instability, lateral displacement of the talus, and even severe ankle osteoarthritis. We present a case of a 16-year-old girl presented with painful swelling over lateral ankle. Radiography revealed an expansile lesion and periosteal reaction over the distal fibula. Magnetic resonance imaging revealed a solitary heterogenous lesion. Histological examination of the open biopsy specimen revealed osteosarcoma. Wide resection and biological reconstruction with allograft followed by skin graft was performed. Over 12-year follow-up, radiography revealed good union. The lateral malleolus allograft appeared to support fair lateral stability over the ankle. The patient had good functional recovery after the long-term follow-up. Osteosarcoma over distal fibula can be treated with wide resection and allograft reconstruction with good functional recovery after long-term follow-up.

BackgroundThe supplemental screw technique was introduced for salvage of lateral hinge fracture in medial open-wedge high tibial osteotomy (owHTO). The efficacy of its use in protection of lateral hinge fracture and corresponding biomechanical behaviors remained unclear. The current study was aimed to clarify if a supplemental screw can provide better protection to lateral hinge in biomechanical perspective.MaterialsAn in vitro biomechanical test was conducted. Tibial sawbones, commercial owHTO plates and a cannulated screw were utilized for preparing the intact, owHTO, and owHTO with cannulated screw insertion specimens. A "staircase" dynamic load protocol was adopted for axial compressive test with increasing load levels to determine structural strength and durability by using a material testing system, while a motion capture system was applied for determining the dynamic changes in varus angle and posterior slope of the tibia plateau with various specimen preparation conditions.ResultsType II lateral hinge fracture were the major failure pattern in all specimens prepared with owHTO. The insertion of a supplemental cannulated screw in medial owHTO specimens reinforced structural stability and durability in dynamic cyclic loading tests: the compressive stiffness increased to 58.9-62.2% of an intact specimen, whereas the owHTO specimens provided only 23.7-29.2% of stiffness of an intact specimen. In view of tibial plateau alignment, the insertion of a supplemental screw improved the structural deficiency caused by owHTO, and reduced the posterior slope increase and excessive varus deformity by 81.8% and 83.2%, respectively.ConclusionThe current study revealed that supplemental screw insertion is a simple and effective technique to improve the structural stability and durability in medial owHTO.

Osteosarcoma is a highly malignant musculoskeletal tumor that is commonly noticed in adolescent children, young children, and elderly adults. Due to advances in surgery, chemotherapy and imaging technology, survival rates have improved to 70–80%, but chemical treatments do not enhance patient survival; in addition, the survival rate after chemical treatments is still low. The most obvious clinical feature of osteosarcoma is new bone formation, which is called “sun burst”. Estrogen receptor alpha (ERα) is an essential feature of osteogenesis and regulates cell growth in various tumors, including osteosarcoma. In this study, we sought to investigate the role of ERα in osteosarcoma and to determine if ERα can be used as a target to facilitate the chemosensitivity of osteosarcoma to current treatments. The growth rate of each cell clone was assayed by MTT and trypan blue cell counting, and cell cycle analysis was conducted by flow cytometry. Osteogenic differentiation was induced by osteogenic induction medium and quantified by ARS staining. The effects of ERα on the chemoresponse of OS cells treated with doxorubicin were evaluated by colony formation assay. Mechanistic studies were conducted by examining the levels of proteins by Western blot. The role of ERα on OS prognosis was investigated by an immunohistochemical analysis of OS tissue array. The results showed an impaired growth rate and a decreased osteogenesis ability in the ERα-silenced P53(+) OS cell line U2OS, but not in P53(−) SAOS2 cells, compared with the parental cell line. Cotreatment with tamoxifen, an estrogen receptor inhibitor, increased the sensitivity to doxorubicin, which decreased the colony formation of P53(+) U2OS cells. Cell cycle arrest in the S phase was observed in P53(+) U2OS cells cotreated with low doses of doxorubicin and tamoxifen, while increased levels of apoptosis factors indicated cell death. Moreover, patients with ER−/P53(+) U2OS showed better chemoresponse rates (necrosis rate > 90%) and impaired tumor sizes, which were compatible with the findings of basic research. Taken together, ERα may be a potential target of the current treatments for osteosarcoma that can control tumor growth and improve chemosensitivity. In addition, the expression of ERα in osteosarcoma can be a prognostic factor to predict the response to chemotherapy.

Allogeneic bone grafts are a promising material for bone implantation due to reduced operative trauma, reduced blood loss, and no donor-site morbidity. Although human decellularized allogeneic bone (hDCB) can be used to fill bone defects, the research of revitalizing hDCB blocks with human mesenchymal stem cells (hMSCs) for osteochondral regeneration is missing. The hMSCs derived from bone marrow, adipose tissue, and Wharton’s jelly (BMMSCs, ADMSCs, and UMSCs, respectively) are potential candidates for bone regeneration. This study characterized the potential of hDCB as a scaffold for osteogenesis and chondrogenesis of BMMSCs, ADMSCs, and UMSCs. The pore sizes and mechanical strength of hDCB were characterized. Cell survival and adhesion of hMSCs were investigated using MTT assay and F-actin staining. Alizarin Red S and Safranin O staining were conducted to demonstrate calcium deposition and proteoglycan production of hMSCs after osteogenic and chondrogenic differentiation, respectively. A RT-qPCR was performed to analyze the expression levels of osteogenic and chondrogenic markers in hMSCs. Results indicated that BMMSCs and ADMSCs exhibited higher osteogenic potential than UMSCs. Furthermore, ADMSCs and UMSCs had higher chondrogenic potential than BMMSCs. This study demonstrated that chondrogenic ADMSCs- or UMSCs-seeded hDCB might be potential osteochondral constructs for osteochondral regeneration.

Giant cell tumors of bone (GCT) are benign tumors that show a locally aggressive nature and affect bones’ architecture. Recently, cryoablation and irradiation treatments have shown promising results in GCT patients with faster recovery and less recurrence and metastasis. Therefore, it became a gold standard surgical treatment for patients. Hence, we have compared GCT-untreated, cryoablation, and irradiation-treated samples to identify protein alterations using high-frequency liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Our label-free quantification analysis revealed a total of 107 proteins (p < 0.01) with 26 up-regulated (< 2-folds to 5-fold), and 81 down-regulated (> 0.1 to 0.5 folds) proteins were identified from GCT-untreated and treated groups. Based on pathway analysis, most of the identified up-regulated proteins involved in critical metabolic functions associated with tumor proliferation, angiogenesis, and metastasis. On the other hand, the down-regulated proteins involved in glycolysis, tumor microenvironment, and apoptosis. The observed higher expressions of matrix metalloproteinase 9 (MMP9) and TGF-beta in the GCT-untreated group associated with bones’ osteolytic process. Interestingly, both the proteins showed reduced expressions after cryoablation treatment, and contrast expressions identified in the irradiation treated group. Therefore, these expressions were confirmed by immunoblot analysis. In addition to these, several glycolytic enzymes, immune markers, extracellular matrix (ECM), and heat shock proteins showed adverse expressions in the GCT-untreated group were identified with favorable regulations after treatment. Therefore, the identified expression profiles will provide a better picture of treatment efficacy and effect on the molecular environment of GCT.

We examined the effects of human umbilical cord-derived mesenchymal stem cells (HUMSCs) in Wharton’s jelly on ovariectomy (OVX)-induced osteoporosis by using in vitro and in vivo experiments. Two months after OVX, the rats gained weight and had a decreased serum estradiol level . Both micro-computed tomography (micro-CT) and histochemical analyses revealed a marked decrease in the bone volume (BV) and collagen content within the head, neck, and distal condyle of the femur, indicating that the osteoporosis animal model was successfully established 2 mo after bilateral OVX. Subsequently, 2.5 × 10 6 HUMSCs were injected into the bone marrow cavity of the left femurs 2 mo after OVX. The rats were divided into the following groups: normal + phosphate-buffered saline (PBS), normal + HUMSCs, OVX + PBS, and OVX + HUMSCs. Two months after transplantation, both micro-CT imaging and histochemical staining revealed that the normal + HUMSCs group had higher BV and collagen content in the epiphysis and metaphysis than did the normal + PBS group. In the OVX + HUMSCs group, a substantial increase in the rod-shaped trabecular bone and the abundant accumulation of collagen were observed around the site of HUMSC transplantation. Plenty of transplanted HUMSCs remained viable and differentiated into osteoblasts. In addition, HUMSC transplantation reduced the number of osteoclasts. Compared with HUMSCs cultured alone, HUMSCs cocultured with osteoblasts showed that the percentage of cells differentiating into osteoblasts significantly increased. Furthermore, osteoclasts cocultured with HUMSCs had significantly decreased cellular activity and differentiation capability. HUMSC transplantation into the distal femur of OVX rats could locally stimulate osteocalcin synthesis, increase the trabecular bone, and inhibit osteoclast activity.

Osteosarcoma (OS) patients who suffer manipulation therapy (MT) prior to diagnosis resulted in poor prognosis with increasing metastasis or recurrence rate. The aim of the study is to establish an in vivo model to identify the effects of MT on OS. The enrolled 235 OS patients were followed up in this study. In vivo nude mice model with tibia injection of GFP-labeled human OS cells were randomly allocated into MT(+) that with repeated massage on tumor site twice a week and no treatment as MT(-) group. The five-year survival, metastasis and recurrence rates were recorded in clinical subjects. X-ray plainfilm, micro-PET/CT scan, histopathology, serum metalloproteinase 2 (MMP2), metalloproteinase 9 (MMP9) level and human kinase domain insert receptor (KDR) pattern were assayed in mice model. The results showed that patient with MT decreased 5-year survival and higher recurrence or metastasis rate. Compatible with clinical findings, the decreased body weight (30.5 ± 0.65 g) and an increased tumor volume (8.3 ± 1.18 mm3) in MT(+) mice were observed. The increasing signal intensity over lymph node region of hind limb by micro-PET/CT and the tumor cells were detected in lung and bilateral lymph nodes only in MT(+) group. MMP2 (214 ± 9.8 ng/ml) and MMP9 (25.5 ± 1.81 ng/ml) were higher in MT(+) group than in MT(-) group (165 ± 7.8 ng/ml and 16.9 ± 1.40 ng/ml, individually) as well as KDR expression. Taking clinical observations and in vivo evidence together, MT treatment leads to poor prognosis of primary osteosarcoma; physicians should pay more attention on patients who seek MT before diagnosis.

Background: Implant-associated Infection remains a major complication of orthopedic surgery. The treatment of such infection is complicated by bacterial biofilm formation on the metal surfaces of implants. Biofilm surrounds and protects the bacteria against the organism's endogenous defense system and from external agents such as antibiotics and mechanical debridement. This study aims to evaluate whether freezing nitrogen ethanol composite (FNEC), the combination of liquid nitrogen and 95% ethanol in a 3 to 1 ratio, used frequently in bone tumor surgery, is capable of disinfecting Staphylococcus aureus contaminated implants. Methods: The femurs of six New Zealand white rabbits were implanted with S. aureus-contaminated screws, half of which were treated with FNEC before implantation. The femurs were harvested 14 days after implantation. Histological analysis and TUNEL assay were conducted. The autoclaved screw, contaminated screw, and FNEC-treated contaminated screw were investigated using scanning electron microscopy to evaluate the biofilm structure. Results: The FNEC-treated group had significantly lower relative C-reactive protein levels. An obvious periosteal reaction at the implant site was observed in all rabbits in the non-FNEC group but none was observed in the FNEC-treated group. The FNEC-treated group exhibited fewer empty lacunae, less inflammatory infiltration, and less bone necrosis. Immunohistochemical analysis showed no S. aureus in bone tissue from the FNEC-treated group. Scanning electron microscopy showed disruption of the biofilm on the contaminated screw treated with FNEC. Conclusion: FNEC showed potential in disinfecting S.aureus-contaminated implants. Further investigation is warranted, such as the effect on the implant-cement-bone interface, for FNEC to be used clinically in treating implant-associated infection. [ABSTRACT FROM AUTHOR]