Osteosarcoma (OS) is the most prevalent bone tumor in children and young adults. Most tumors arise from the metaphysis of the long bones and easily metastasize to the lungs. Current therapeutic strategies of osteosarcoma are routinely surgical resection and chemotherapy, which are limited to the patients suffering from metastatic recurrence. Therefore, to investigate molecular mechanisms that contribute to osteosarcoma progression is very important and may shed light on targeted therapeutic approach to improve the survival of patients with this disease. Several miRNAs have been found expressed differentially in osteosarcoma (OS), In this study, we found that miR-144 significantly suppresses osteosarcoma cell proliferation, migration andinvasion ability in vitro, and inhibited tumor growth and metastasisin vivo. The function and molecular mechanism of miR-144 in Osteosarcoma was further investigated. Tissue samples from fifty-one osteosarcoma patients were obtained from Shanghai Ninth People's Hospital. The in vitro function of miR-144 in Osteosarcoma was investigated by cell viability assay, wound healing assay, invasion assay, the molecular mechanism was identified by Biotin-coupled miRNA capture, Dual-luciferase reporter assays, etc. the in vivo function of miR-144 in osteosarcoma was confirmed by osteosarcoma animal model and miR-144−/− zebrafish model. Mechanically, we demonstrated that Ras homolog family member A (RhoA) and its pivotal downstream effector Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) were both identified as direct targets of miR-144. Moreover, the negative co-relation between downregulated miR-144 and upregulated ROCK1/RhoA was verified both in the osteosarcoma cell lines and clinical patients' specimens. Functionally, RhoA with or without ROCK1 co-overexpression resulted a rescue phenotype on the miR-144 inhibited cell growth, migration and invasion abilities, while individual overexpression of ROCK1 had no statistical significance compared with control in miR-144 transfected SAOS2 and U2-OS cells. This study demonstrates that miR-144 inhibited tumor growth and metastasis in osteosarcoma via dual-suppressing of RhoA and ROCK1, which could be a new therapeutic approach for the treatment ofosteosarcoma.
The aim of this study was to determine the impact of the severity of anaemia on postoperative complications following total hip arthroplasty (THA) and total knee arthroplasty (TKA). A retrospective cohort study was conducted using the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) database. All patients who underwent primary TKA or THA between January 2012 and December 2017 were identified and stratified based upon hematocrit level. In this analysis, we defined anaemia as packed cell volume (Hct) < 36% for women and < 39% for men, and further stratified anaemia as mild anaemia (Hct 33% to 36% for women, Hct 33% to 39% for men), and moderate to severe (Hct < 33% for both men and women). Univariate and multivariate analyses were used to evaluate the incidence of multiple adverse events within 30 days of arthroplasty.Aims
Methods
Accurate placement of the glenoid component in total shoulder arthroplasty (TSA) is critical to optimize implant longevity. Commercially available patient-specific instrumentation systems can improve implant placement, but may involve considerable expense and production delays of up to six weeks. The purpose of this study was to develop a novel technique for in-house production of 3D-printed, patient-specific glenoid guides, and compare the accuracy of glenoid guidepin placement between the patient-specific guide and a standard guide using a cadaveric model. Twenty cadaveric shoulder specimens were randomized to receive glenoid guidepin placement via standard TSA guide (Wright Medical, Memphis, TN) or patient-specific guide. Three-dimensional scapular models were reconstructed from CT scans with Mimics 20.0 imaging software (Materialise NV, Leuven, Belgium). A pre-surgical plan was created for all specimens for the central glenoid guidepin of 0º version and inclination angles. Central pin entry and exit points were also calculated. Patient-specific guides were constructed to achieve the planned pin trajectory in Rhino3D software (Robert McNeel & Associates, Seattle, WA). Guides were 3D-printed on a Form2 printer with Formlabs Dental SG Resin (Formlabs, Somerville, MA). Glenoid labrum and cartilage were removed with preservation of other soft tissues in all specimens to mimic intraoperative TSA conditions. A fellowship-trained, board-eligible orthopaedic surgeon placed a 2.5 mm diameter titanium guidepin into each glenoid using the assigned guide for each specimen. After pin placement, repeat CT scans were performed, and a blinded measurer used superimposed 3D scapular reconstructions to calculate deviation from the pre-surgical plan in version and inclination angles, dot product angle, and guide pin entry and exit points. Student's t tests were performed to detect differences between pin placements for the two groups.Background
Methods
Tranexamic acid (TXA), an inhibitor of fibrinolysis blocking the lysine-binding site of plasminogen to fibrin, has been reported to reduce intraoperative and postoperative blood loss in patients undergoing primary total hip arthroplasty (PTHA) both with and without cement. Both intravenous (IV) and topical (TOP) administration of TXA can effectively reduce blood loss in THA without increasing risk of deep venous thrombosis (DVT). However, there have been few reports investigating the combination of intravenous and topical administration of TXA in bilateral cementless PTHA. We investigated the effects of combined intravenous and topical administration of TXA on postoperative blood loss, drainage volume, and perioperative complications in patients with bilateral simultaneous cementless PTHA for hip osteoarthritis. We retrospectively reviewed the demographic and clinical data of 41 patients who underwent bilateral simultaneous cementless PTHA for hip osteoarthritis from May 2015 to January 2017, of which there were 29 male (70.7%) and 12 female (29.3%) patients. Patients in IV group (n= 11) received only TXA (15 mg/kg) 10 min prior to the incision of each side; and patients in IV + TOP group (n=13) received i.v. TXA (15 mg/kg) combined with topical adiministration (1.0 g) of TXA during the each THA procedure; patients in control group (n=17) received the same dosage of normal saline both i.v. and topically. Outcome measures were total blood loss, hemoglobin, hematocrit value (HCT) changes preoperatively, and on the 1st, 3rd postoperative day, the amount of drainage, and perioperative complications.Objectives
Patients and methods
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.Background
Methods
Articular cartilage repair remains a challenge in orthopedic surgery, as none of the current clinical therapies can regenerate the functional hyaline cartilage tissue. In this study, we proposed a one-step surgery strategy that uses autologous bone marrow mesenchymal stem cells (MSCs) embedded in type II collagen (Col-II) gels to repair the full thickness chondral defects in minipig models. Briefly, 8 mm full thickness chondral defects were created in both knees separately, one knee received Col-II + MSCs transplantation, while the untreated knee served as control. At 1, 3 and 6 months postoperatively, the animals were sacrificed, regenerated tissue was evaluated by magnetic resonance imaging, macro- and microscopic observation, and histological analysis. Results showed that regenerated tissue in Col-II + MSCs transplantation group exhibited significantly better structure compared with that in control group, in terms of cell distribution, smoothness of surface, adjacent tissue integration, Col-II content, structure of calcified layer and subchondral bone. With the regeneration of hyaline-like cartilage tissue, this one step strategy has the potential to be translated into clinical application.
Heterotopic ossification (HO) is a known complication following total hip arthroplasty, with increased incidence in certain patient populations. Current prophylaxis options include oral non-steroidal anti-inflammatory drugs (NSAIDs) and radiation therapy, but an optimal radiation protocol has yet to be clearly defined. We performed a randomized, double-blinded clinical trial in high-risk total hip arthroplasty patients to determine the efficacy of 400 cGy versus 700 cGy doses of radiation. 147 patients at high risk for HO undergoing total hip arthroplasty (THA) at Rush-St. Luke's- Presbyterian medical center were randomized to either a single 400 cGy or 700 cGy dose of radiation. High risk was defined as diagnosis of diffuse idiopathic skeletal hyperostosis (DISH), hypertrophic osteoarthritis, ankylosing spondylitis, or history of previous heterotopic ossification. Radiation was administered over a 14 × 6 cm area of soft tissue and given on the first or second post-operative day. A blinded reviewer graded anterior-posterior (AP) and lateral radiographs taken immediately post-operatively and at a minimum of 6 months post-operatively. Progression was defined as an increase in Brooker classification from the immediate post-operative to the long-term post-operative radiograph. Operative data including surgical approach, use of cemented implants, revision surgery, and post-operative range of motion data were also collected.Background
Methods
The development of T-smart tomosynthesis has greatly improved the imaging quality of THA by reducing the peri-implant artifacts. In order to find out whether these improvements could lead to diagnostic advantages on stability of cementless THA arthroplasty components, we conducted a diagnostic research by comparing T-smart tomosynthesis, X-ray, and computed tomography. We retrospectively included 48 patients who undergone THA revisions in our center between Aug, 2013 and Mar, 2014. For patients with hybrid fixation as their primary prosthesis, the femoral or acetabular components with cement fixation were excluded. There were 41 cementless femoral stems and 35 cementless acetabular cups remained for evaluation. All patients took anterior-posterior and lateral view x-ray examination, anterior-posterior T-smart tomosynthesis scan, and computed tomography before revision surgery. As the gold standard, intraoperative pull-out tests and twisting tests were done for every patient to examine the stability of all implants. 7 orthopedic surgeons evaluated the preoperative images independently, who were divided into the senior group (3 doctors with 6∼13 years’ clinical experience) and the junior group (4 doctors with 2∼4 years’ clinical experience). The x-rays were evaluated first, followed by computed tomography 4 weeks later, and after another 4 weeks’ interval the T-smart tomosynthesis were assessed. All doctors used the same criteria for diagnosis. Diagnostic accuracy for each imaging examination was calculated by comparing with the results of intraoperative tests. The diagnostic accuracy, kappa values between 3 imaging techniques were calculated, and chi-square tests were conducted to examine the difference between the senior and junior groups for each technique.Background
Methods
While indications for total knee (TKA) and hip arthroplasty (THA) have expanded over the last 35 years, implant labeling has largely remained stagnant, with conditions including obesity, developmental dysplasia, and many others (Table 1) still considered as contraindications. Implant labeling has not co-evolved with surgical indications, as most orthopaedic implants are cleared through the 510(k) process, which conserves the labeling of the predicate device. While surgeons can legally use devices for off-label indications, the scrutiny regarding off-label use of orthopaedic implants has intensified. The objective of this study was to determine the incidence of off-label use at our institution, define the risk in terms of revision rate associated with off-label use, and to compare activity level, functional outcomes, and general health outcomes for on- and off-label TKA and THA patients. Patients who underwent primary TKA or THA at a large academic tertiary referral center between January 1, 2010 and June 30, 2010 were considered for the study (n = 705). Of this cohort, a convenience sample of 283 patients were selected for the study based on the presence of baseline outcomes data. Patients were contacted via mail and/or phone to collect details regarding potential revision surgeries, UCLA activity scores, short form-12 (SF-12), Knee Injury and Osteoarthritis Outcome Score (KOOS) or Hip Disability and Osteoarthritis Outcome Score (HOOS). Using labeled contraindications from the product inserts from multiple orthopaedic implant manufacturers, procedures were categorized as on-label or off-label. Outcomes including revision rate, activity score, and SF-12, KOOS, and HOOS scores were adjusted for age, gender, and BMI by fitting a logistic model and analyzed using the Wald chi-square test (SPSS, Chicago, IL).Introduction:
Methods:
