TGF-β/Smad2 signaling is considered to be one of the important pathways involved in osteoarthritis (OA) and protein phosphatase magnesium-dependent 1A (PPM1A) functions as an exclusive phosphatase of Smad2 and regulates TGF-β signaling, here, we investigated the functional role of PPM1A in OA pathogenesis. PPM1A expressions in both human OA cartilage and experimental OA mice chondrocytes were analyzed immunohistochemically. Besides, the mRNA and protein expression of PPM1A induced by IL-1β treatment were also detected by q-PCR and immunofluorescence in vitro. OA was induced in PPM1A knockout (KO) mice by destabilization of the medial meniscus (DMM), and histopathological examination was performed. OA was also induced in wild-type (WT) mice, which were then treated with an intra-articular injection of a selective PPM1A inhibitor for 8 weeks. PPM1A protein expressions were increased in both human OA cartilage and experimental OA mice chondrocytes. We also found that treatment with IL-1β in mouse primary chondrocytes significantly increased both mRNA and protein expression of PPM1A in vitro. Importantly, our data showed that PPM1A deletion could substantially protect against surgically induced OA. Concretely, the average OARSI score and quantification of BV/TV of subchondral bone in KO mice were significantly lower than that in WT mice 8 weeks after DMM surgery. Besides, TUNEL staining revealed a significant decrease in apoptotic chondrocytes in PPM1A-KO mice with DMM operation. With OA induction, the rates of chondrocytes positive for Mmp-13 and Adamts-5 in KO mice were also significantly lower than those in WT mice. Moreover, compared with WT mice, the phosphorylation of Smad2 in chondrocytes was increased in KO mice underwent DMM surgery. However, articular-injection with SD-208, a selective inhibitor of TGF-β/Smad2 signaling could significantly abolish the chondroprotective phenotypes in PPM1A-KO mice. Additionally, both cartilage degeneration and subchondral bone subchondral bone sclerosis in DMM model were blunted following intra-articular injection with BC-21, a small-molecule inhibitor for PPM1A. Our study demonstrated that PPM1A inhibition attenuates OA by regulating TGF-β/Smad2 signaling. Furthermore, PPM1A is a potential target for OA treatment and BC-21 may be employed as alternative therapeutic agents for the management of OA.
Using deep learning and image processing technology, a standardized automatic quantitative analysis systerm of lumbar disc degeneration based on T2MRI is proposed to help doctors evaluate the prognosis of intervertebral disc (IVD) degeneration. A semantic segmentation network BianqueNet with self-attention mechanism skip connection module and deep feature extraction module is proposed to achieve high-precision segmentation of intervertebral disc related areas. A quantitative method is proposed to calculate the signal intensity difference (SI) in IVD, average disc height (DH), disc height index (DHI), and disc height-to-diameter ratio (DHR). According to the correlation analysis results of the degeneration characteristic parameters of IVDs, 1051 MRI images from four hospitals were collected to establish the quantitative ranges for these IVD parameters in larger population around China. The average dice coefficients of the proposed segmentation network for vertebral bodies and intervertebral discs are 97.04% and 94.76%, respectively. The designed parameters of intervertebral disc degeneration have a significant negative correlation with the Modified Pfirrmann Grade. This procedure is suitable for different MRI centers and different resolution of lumbar spine T2MRI (ICC=.874~.958). Among them, the standard of intervertebral disc signal intensity degeneration has excellent reliability according to the modified Pfirrmann Grade (macroF1=90.63%~92.02%). we developed a fully automated deep learning-based lumbar spine segmentation network, which demonstrated strong versatility and high reliability to assist residents on IVD degeneration grading by means of IVD degeneration quantitation.
The optimal procedure for the treatment of ossification of the posterior longitudinal ligament (OPLL) remains controversial. The aim of this study was to compare the outcome of anterior cervical ossified posterior longitudinal ligament en bloc resection (ACOE) with posterior laminectomy and fusion with bone graft and internal fixation (PTLF) for the surgical management of patients with this condition. Between July 2017 and July 2019, 40 patients with cervical OPLL were equally randomized to undergo surgery with an ACOE or a PTLF. The clinical and radiological results were compared between the two groups.Aims
Methods
The purpose of this study is to report the overall infection control rate and prognostic factors associated with acute, hematogenous and chronic PJIs treated with DAIR. All DAIR procedures performed at 2 institutions from 2009 to 2018 (n=104) were reviewed and numerous data were recorded, including demographics, preoperative laboratory tests, Charleston Comorbidity Index, surgical information and organism culture results. Treatment success was defined according to the criteria reported by Diaz-Ledezma. A multivariable analysis was utilized to identify prognostic factors associated with treatment and a Kaplan-Meier survival analysis was used to depict infection control rate as a function of time.Aim
Methods
Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA. OA animal model was induced by destabilization of the medial meniscus (DMM). Different concentrations of tBHQ (25 and 50 mg/kg) were intraperitoneally injected in ten-week-old female mice. Chondrocytes were isolated from articular cartilage of mice and treated with 5 ng/ml lipopolysaccharide (LPS) or 10 ng/ml interleukin 1 beta (IL-1β) for 24 hours, and then treated with different concentrations of tBHQ (10, 20, and 40 μM) for 12 hours. The expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured. The expression levels of interleukin 6 (IL-6), IL-1β, and tumour necrosis factor alpha (TNF-α) leptin in plasma were measured using enzyme-linked immunoabsorbent assay (ELISA) kits. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway proteins, and macrophage repolarization-related markers, were detected by western blot.Aims
Methods
Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining.Aims
Methods
It can be extremely challenging to determine whether to perform reimplantation in patients who have contradictory serum inflammatory markers and frozen section results. We investigated whether patients with a positive frozen section at reimplantation were at a higher risk of reinfection despite normal ESR and CRP. We retrospectively reviewed 163 consecutive patients with periprosthetic joint infections (PJIs) who had normal ESR and CRP results pre-reimplantation in our hospital from 2014 to 2018. Of these patients, 26 had positive frozen sections at reimplantation. The minimum follow-up time was two years unless reinfection occurred within this period. Univariable and multivariable logistic regression analyses were performed to identify the association between positive frozen sections and treatment failure.Aims
Methods
Primary robotic-arm assisted total hip arthroplasty (THA) yields more accurate and reproducible acetabular cup placement, nonetheless, data is scarce in terms of outcomes. The purpose of the present study was to report on patient-reported outcomes (PROMs) in a large group of patients who underwent robotic-arm assisted THA. The authors hypothesized that (1) patients who underwent robotic-arm assisted primary THA would achieve favorable and significant improvement in PROMs, (2) an accurate and reproducible acetabular cup placement with respect to the defined SafeZones would be obtained, and (3) a low rate of THA dislocation would be observed. Prospectively collected data were retrospectively reviewed between April 2012 to May 2017. Primary THA using Mako Robotic-Arm [Mako Surgical Corp. (Stryker), Fort Lauderdale, FL, USA] with minimum two-year follow-up for the Harris Hip Score (HHS) and the Forgotten Joint Score-12 (FJS-12) were included. Exclusion criteria were: bodymass index (BMI) > 40 kg/m2, age < 21-year old, worker's compensation, or unwilling to participate. Visual analog scale (VAS) for pain and patient satisfaction were obtained. Intraoperative measurements for leg-length, global offset, acetabular inclination and version were documented.Introduction
Methods
The aim of this study was to further evaluate the accuracy of ten promising synovial biomarkers (bactericidal/permeability-increasing protein (BPI), lactoferrin (LTF), neutrophil gelatinase-associated lipocalin (NGAL), neutrophil elastase 2 (ELA-2), α-defensin, cathelicidin LL-37 (LL-37), human β-defensin (HBD-2), human β-defensin 3 (HBD-3), D-dimer, and procalcitonin (PCT)) for the diagnosis of periprosthetic joint infection (PJI), and to investigate whether inflammatory joint disease (IJD) activity affects their concentration in synovial fluid. We included 50 synovial fluid samples from patients with (n = 25) and without (n = 25) confirmed PJI from an institutional tissue bank collected between May 2015 and December 2016. We also included 22 synovial fluid samples aspirated from patients with active IJD presenting to Department of Rheumatology, the first Medical Centre, Chinese PLA General Hospital. Concentrations of the ten candidate biomarkers were measured in the synovial fluid samples using standard enzyme-linked immunosorbent assays (ELISA). The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curves.Aims
Methods
Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model. Mesenchymal stem cells (MSCs) were isolated from ageing patients and preconditioned with chondrogenic differentiation medium, followed by normal growth medium. Cellular assays including Bromodeoxyuridine / 5-bromo-2'-deoxyuridine (BrdU), quantitative polymerase chain reaction (q-PCR), β-Gal, Rosette forming, and histological staining were compared in the manipulated human mesenchymal stem cells (hM-MSCs) and their controls. The anterior cruciate ligament transection (ACLT) rabbit models were locally injected with two millions, four millions, or eight millions of hM-MSCs or phosphate-buffered saline (PBS). Osteoarthritis Research Society International (OARSI) scoring was performed to measure the pathological changes in the affected joints after staining. Micro-CT analysis was conducted to determine the microstructural changes in subchondral bone.Aims
Methods
Growth factors are reported to play an important role in healing after acute Achilles tendon rupture (ATR). However, the association between growth factors and patient outcome has not been investigated previously. The aim of this retrospective study is to identify growth factors and related proteins which can be used as predictors of healing after ATR, ethical approval was obtained from the Regional Ethical Review Committees in Sweden and followed the guidelines of the Declaration of Helsinki. The study included 28 surgically treated patients (mean age 39.11 ± 8.38 yrs) with acute ATR. Healing was assessed by microdialysate two weeks after the surgery and performed on both injured and contralateral un-injured leg. The microdialysates were analyzed by proteomics based on mass spectrometry (MS) to detect growth factor expressions in ATR patients. One year after the surgery, healing outcomes were evaluated by patient-reported Achilles tendon Total Rupture Score (ATRS), Foot and Ankle Outcome Score (FAOS), and functional outcomes by heel-rise test. A total of 1549 proteins were detected in the microdialysates of which 20 growth factor/ related proteins were identified. 7 of these were significantly up-regulated (IGFBP2, Fold change (FC) = 4.07, We conclude that growth factors and related proteins play a crucial role in ATR healing. More specifically, TGFB1 may be used as prognostic biomarker of the patient-reported outcome 1-year post-surgery. These results may be used to develop more specific treatments to improve ATR healing.
The purpose of this study was to validate our hypothesis that centrifugation may eliminate false-positive leucocyte esterase (LE) strip test results caused by autoimmune diseases in the diagnosis of knee infection. Between January 2016 and May 2019, 83 cases, including 33 cases of septic arthritis and 50 cases of aseptic arthritis, were enrolled in this study. To further validate our hypothesis, another 34 cases of inflammatory arthritis from the Department of Rheumatology of our institution were also included. After aspiration, one drop of synovial fluid was applied to LE strips before and after centrifugation. The results were recorded after approximately three minutes according to the different colour grades on the colour chart. The differences of LE results between each cohort were analyzed.Aims
Methods
Acetabular cup positioning remains a real challenge and component malpositioning after total hip arthroplasty (THA) can lead to increased rates of dislocation and wear. It is a common cause for revision THA. A novel 3D imageless mini-optical navigation system was used during THA to provide accurate, intraoperative, real-time, and non-fluoroscopic data including component positioning to the surgeon. This retrospective comparative single surgeon and single approach study examined acetabular component positioning between traditional mini-posterolateral THA and mini-posterolateral THA using the 3D mini-optical navigation system. A retrospective chart review was conducted of 157 consecutive (78 3D mini-optical navigation and 79 traditional non-navigation methods) THAs performed by the senior author using a mini-posterolateral approach at an ambulatory surgery center and hospital setting. Two independent reviewers analyzed postoperative radiographs in a standardized fashion to measure acetabular component positioning. Demographic, clinical, surgical, and radiographic data were analyzed. These groups were found to have no statistical difference in age, gender, and BMI (Table I). There was no difference between groups in acetabular components in the Lewinnek safe zone, 31.2% vs 26.6% ( For any figures or tables, please contact the authors directly.
This study aimed to explore whether intraoperative nerve monitoring can identify risk factors and reduce the incidence of nerve injury in patients with high-riding developmental dysplasia. We conducted a historical controlled study of patients with unilateral Crowe IV developmental dysplasia of the hip (DDH). Between October 2016 and October 2017, intraoperative nerve monitoring of the femoral and sciatic nerves was applied in total hip arthroplasty (THA). A neuromonitoring technician was employed to monitor nerve function and inform the surgeon of ongoing changes in a timely manner. Patients who did not have intraoperative nerve monitoring between September 2015 and October 2016 were selected as the control group. All the surgeries were performed by one surgeon. Demographics and clinical data were analyzed. A total of 35 patients in the monitoring group (ten male, 25 female; mean age 37.1 years (20 to 46)) and 56 patients in the control group (13 male, 43 female; mean age 37.9 years (23 to 52)) were enrolled. The mean follow-up of all patients was 13.1 months (10 to 15).Aims
Patients and Methods
Patient-specific instrumentation (PSI) is a novel technique in total knee arthroplasty (TKA) which potentially permits more accurate alignment of the components; however, there is no consensus in literature regarding the accuracy and reliability of PSI as many studies have shown controversial and inconsistent results of various PSI systems. A 24-month follow-up study was carried out to compare perioperative clinical outcomes, radiological limb alignment and component positioning, as well as functional outcomes following TKA between PSI and conventional instrumentation (CI). During September 2011 and August 2012, 90 consecutive patients were scheduled to undergo unilateral TKA with either PSI or CI. TruMatch® Personalised Solutions was used in this study, and a senior surgeon performed all operations. Patients were clinically assessed before, 6-month and 24-month after surgery.Objective
Methods
Failures in total knee arthroplasty (TKA) have been associated with overall lower limb malalignment and component malposition. Although traditional computer navigation systems improve component placement, they require fixation of the femoral and tibial reference arrays for software recognition using anchoring pins. This increases the risk of bony fracture, pin sites infection and osteomyelitis. This study aims to evaluate the accuracy of a new hand held navigation system (BrainLAB® Dash® Navigation system) that will avoid these complications.Introduction
Aim
Standard image-free navigation systems have proven to improve the accuracy of components placement and reduce the proportion of outliers for lower limb mechanical axis in total knee arthroplasty (TKA). However, their disadvantages include a longer duration of surgery and pin-tract related complications. More recently, pinless navigation has been developed to address these shortcomings. This study aims to investigate the effectiveness of a new pinless navigation system (Zimmer® iAssist™ Knee) in TKA. Power analysis was performed. To detect a significant difference in the proportion of outliers for lower limb mechanical axis at a power of 0.80, a sample size of 50 patients would be required. Between May 2013 and April 2014, 50 patients diagnosed with osteoarthritis of the knee were divided into two surgical technique arms: 1) iAssist™; 2) conventional TKA. One Adult Reconstruction surgeon performed all the surgeries. The patients were prospectively followed up and postoperative long leg radiographs were taken at one month post-surgery. Two reviewers blinded to the surgical method performed the measurements on radiographic films. Five radiographic measurements were measured: 1) Hip-Knee-Ankle Angle (HKA); 2) Coronal Femoral-Component Angle (CFA); 3) Coronal Tibia-Component Angle (CTA); 4) Sagittal Femoral-Component Angle (SFA); and 5) Sagittal Tibia-Component Angle (STA), The Mann-Whitney U test was used to compare the two groups for quantitative variables while the Fisher's exact test was used for categorical variables.Introduction
Methods
This study compares outcomes of vertebroplasty(VP) and kyphoplasty(KP) in 125 consecutive female Asian patients above 65 years with L1 osteoporotic vertebral compression fractures 57 and 68 patients underwent VP and KP respectively from 2004 to 2008. Outcomes were measured prospectively at pre-operation, 1 month, 6 months and 2 years post-operation by blinded assessors. Radiographic outcome: Anterior, middle and posterior vertebral heights of the L1 vertebral body Functional outcome: Short-Form 36(SF-36) score, Visual Analogue Scale(VAS) score for back painIntroduction
Methods
The risk factors for new adjacent vertebral compression fracture (NAVCF) after Vertebroplasty (VP) or Kyphoplasty (KP) for osteoporotic vertebral compression fractures (VCFs) were investigated. The authors retrospectively analyzed the incidence of NAVCFs in 135 patients treated with VP or KP for osteoporotic VCFs. Study period was from 2004 to 2008 with minimum follow-up of 2 years. Possible risk factors were documented: age, gender, body mass index, bone mineral density (BMD), co-morbidities, location of treated vertebra, treatment modality and amount of bone cement injected. Anterior-posterior vertebral body height ratio, intra-discal cement leakage into the disc space and pattern of cement distribution of the initial VCF and adjacent vertebral bodies were assessed on lateral thoracolumbar radiographs by 2 independent assessors.Introduction
Materials and methods
Total knee arthroplasty (TKA) has proven to be cost-effective and efficative in the treatment of osteoarthritic knees. Although traditional computer navigation systems improve implant placement, they require fixation of the femoral and tibial reference arrays for software recognition using anchoring pins. This increases the risk of bony fracture, pin sites infection and osteomyelitis. Our study aims to investigate the accuracy of a new inless navigation system (Brainlab VectorVision Knee 2.5 Navigation System) that would avoid these complications. 119 patients were prospectively recruited over a year. These patients all underwent a primary TKA by a senior surgeon who performs more than 200 TKAs per annum. They were divided into two surgical technique arms. In Group 1, 74 patients underwent TKA using conventional techniques. In Group 2, 45 patients underwent TKA using a pinless navigation system. Post-operative films were taken and three radiographic measurements were measured: 1) Hip-Knee-Ankle Angle (HKA); 2) Coronal Femoral-Component Angle (CFA); 3) Coronal Tibia-Component Angle (CTA) (Figure 1). Two reviewers blinded to the surgical method performed the measurements on the radiographic films on two separate occasions.Introduction
Methods
