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Bone & Joint Research
Vol. 13, Issue 4 | Pages 157 - 168
4 Apr 2024
Lin M Chen G Yu H Hsu P Lee C Cheng C Wu S Pan B Su B

Aims

Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro.

Methods

MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry.


Bone & Joint Research
Vol. 11, Issue 6 | Pages 386 - 397
22 Jun 2022
Zhu D Fang H Yu H Liu P Yang Q Luo P Zhang C Gao Y Chen Y

Aims

Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood.

Methods

MicroRNA (miR) sequencing was performed on bone mesenchymal stem cells (BMSCs). The effects of alcohol and miR-19a-3p on vascularization and osteogenic differentiation were analyzed in vitro using BMSCs and human umbilical vein endothelial cells (HUVECs). An in vivo alcohol-fed mouse model of femur fracture healing was also established, and radiological and histomorphometric analyses were used to evaluate the role of miR-19a-3p. The binding of miR-19a-3p to forkhead box F2 (FOXF2) was analyzed using a luciferase reporter assay.


Aims

Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have been reported to be a promising cellular therapeutic approach for various human diseases. The current study aimed to investigate the mechanism of BMSC-derived exosomes carrying microRNA (miR)-136-5p in fracture healing.

Methods

A mouse fracture model was initially established by surgical means. Exosomes were isolated from BMSCs from mice. The endocytosis of the mouse osteoblast MC3T3-E1 cell line was analyzed. CCK-8 and disodium phenyl phosphate microplate methods were employed to detect cell proliferation and alkaline phosphatase (ALP) activity, respectively. The binding of miR-136-5p to low-density lipoprotein receptor related protein 4 (LRP4) was analyzed by dual luciferase reporter gene assay. HE staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemistry were performed to evaluate the healing of the bone tissue ends, the positive number of osteoclasts, and the positive expression of β-catenin protein, respectively.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_10 | Pages 38 - 38
1 Oct 2020
Suter LG Yu H Zywiel MG Li L Lin Z Simoes JL Sheares KD Grady J Bernheim S Bozic K
Full Access

Introduction

Quality measures play a substantial role in the Centers for Medicare and Medicaid Services' hospital payment and public reporting programs. The purpose of this study was to assess whether public measurement of total hip and knee arthroplasty risk-standardized readmission (RSRRs) and complication rates (RSCRs) was temporally associated with decreasing rates of adverse outcomes among Medicare beneficiaries.

Methods

We evaluated annual trends in hospital-level risk-standardized complication and readmission rates in the fiscal years 2010–11 and 2016–17 for patients undergoing hospital-based inpatient hip/knee replacement procedures. We calculated hospital-level rates using the same measures and methodology used in public reporting. We examined annual trends in the distribution of hospital-level outcomes through density plots (similar to histograms).


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 28 - 28
1 Dec 2018
Gottschalk F Heinrich KH Yu H Wilke T
Full Access

Aim

Surgical site infections caused by Staphylococcus aureus (S. aureus) are associated with considerable clinical and economic burden. Studies assessing this burden in Germany have been limited to specific institutions, selected patient groups or not specific to S. aureus infections (SAI). This study was undertaken to further understand the burden of SAI following orthopedic surgeries in Germany.

Method

All patients with at least one spine, endoprosthetic hip or knee surgery between 2012 and 2015 captured in the AOK PLUS claims database were included in this analysis. SAI were identified using S. aureus-specific ICD-10 codes following surgery. Exclusion criteria included: younger than 18, SAI in the 90 days preceding index, any surgery in the 180 days preceding index, surgery at the same body location as index in the preceding 365 days, or more than one surgery of interest during index hospitalization.

Cumulative incidence and incidence density were used to assess SAI. Mortality, healthcare resource utilization and costs were compared between SAI and non-SAI group during the 1year follow-up post index surgery. Multivariate analyses were conducted while controlling for sex, age, Charlson Comorbidity Index (CCI), location of surgery, length of index hospitalization, recent fractures, other bacterial infections during index hospitalization and outpatient prescriptions for antibiotics in the year pre-index.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_15 | Pages 26 - 26
1 Oct 2014
Molloy S Butler J Yu H Sewell M Benton A Selvadurai S Agu O
Full Access

To assess implant performance, to evaluate fusion and to assess clinical and radiologic outcome of circumferential fusion using porous tantalum cages for ALIF in a 360-degree fusion.

A retrospective cohort study was performed over a 4-year period that included the implantation of 280 tantalum cages in 98 patients by the technique of anterior lumbar interbody fusion (ALIF) and posterolateral spondylodesis. Radiographic follow-up was performed to document any implant related problems. Preoperative and postoperative clinical outcome measures were assessed.

No neurological, vascular or visceral injuries were reported. There were no rod breakages and no symptomatic non-unions. One revision procedure was performed for fracture. Mean VAS back pain score in our patient cohort improved from 7.5 preoperatively to 1.9 at latest follow-up, mean VAS leg pain score improved from 6.2 to 1.1 and mean ODI score improved from 51.1 to 18.3.

Porous tantalum cages have high strength and flexibility, in addition to having similar biomaterial properties to cancellous bone. Their use in 360-degree spondylodesis to treat degenerative lumbar spine deformity has been demonstrated to be very safe and effective, with excellent clinical and functional outcomes.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_15 | Pages 27 - 27
1 Oct 2014
Molloy S Butler J Yu H Selvadurai S Panchmatia J
Full Access

To evaluate the incidence of complications and the radiographic and clinical outcomes from 2-stage reconstruction including 3-column osteotomy for revision adult spinal deformity.

A prospective cohort study performed over 2 years at a major tertiary referral centre for adult spinal deformity surgery. All consecutive patients requiring 2-stage corrective surgery for revision adult spinal deformity were included. Radiographic parameters and clinical outcome measures were collected preoperatively and at 6 weeks, 6 months, 1 year and 2 years postoperatively. Radiographic parameters analysed included pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, thoracic kyphosis and sagittal vertical axis. Clinical outcome measures collected included EQ-5D, ODI, SRS 22 and VAS Pain Scores.

Performing anterior column reconstruction followed by 3-column osteotomy and extension of instrumentation for revision spinal deformity resulted an excellent correction of sagittal alignment, minimal surgical complications and significant improvements in HRQOL. Restoration of lumbar lordosis, pelvic tilt and sagittal vertical axis were observed in addition to postoperative improvements in EQ-5D, ODI, SRS 22 and VAS Pain Scores at follow-up.

Performing anterior column reconstruction prior to a 3-column osteotomy minimises complications associated with 3-column osteotomy and extension of posterior instrumentation. We propose a treatment algorithm for safe and effective treatment in revision adult deformity surgery.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_15 | Pages 23 - 23
1 Oct 2014
Molloy S Butler J Yu H Benton A Selvadurai S
Full Access

To evaluate the differences between spinopelvic parameters before and after sagittal malalignment correction and to assess the relationship between these radiologic parameters and clinical outcome scores.

A prospective cohort study was performed over a 2-year period at a major tertiary referral centre for adult spinal deformity surgery. All consecutive patients requiring 2-stage corrective surgery were included (n=32). Radiographic parameters and clinical outcome measures were collected preoperatively and at 6 weeks, 6 months, 1 year and 2 years postoperatively. Radiographic parameters analysed included pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, thoracic kyphosis and sagittal vertical axis. Clinical outcome measures collected included EQ-5D, ODI, SRS 22 and VAS Pain Scores.

Correction of sagittal malalignment was associated with significant improvements in HRQOL. Restoration of lumbar lordosis, pelvic tilt and sagittal vertical axis correlated with postoperative improvements in EQ-5D, ODI, SRS 22 and VAS Pain Scores at follow-up.

This study demonstrates that the magnitude of sagittal plane correction correlates with the degree of clinical improvements in HRQOL. This further underlines the need for spinal surgeons to target complete sagittal plane deformity correction if they wish to achieve the highest rates of HRQOL benefit in patients with marked sagittal malalignment.