Dickkopf-1 (DKK1) blockade mitigates osteogenesis imperfecta (OI) related bone disease.

BACKGROUND: The current treatment of osteogenesis imperfecta (OI) is imperfect. Our study thus delves into the potential of using Dickkopf-1 antisense (DKK1-AS) to treat OI. METHODS: We analysed serum DKK1 levels and their correlation with lumbar spine and hip T-scores in OI patients. Comparative analyses were conducted involving bone marrow stromal cells (BMSCs) and bone tissues from wild-type mice, untreated OI mice, and OI mice treated with DKK1-ASor DKK1-sense (DKK1-S). RESULTS: Significant inverse correlations were noted between serum DKK1 levels and lumbar spine (correlation coefficient = - 0.679, p = 0.043) as well as hip T-scores (correlation coefficient = - 0.689, p = 0.042) in OI patients. DKK1-AS improved bone mineral density (p = 0.002), trabecular bone volume/total volume fraction (p < 0.001), trabecular separation (p = 0.010), trabecular thickness (p = 0.001), trabecular number (p < 0.001), and cortical thickness (p < 0.001) in OI mice. DKK1-AS enhanced the transcription of collagen 1α1, osteocalcin, runx2, and osterix in BMSC from OI mice (all p < 0.001), resulting in a higher von Kossa-stained matrix area (p < 0.001) in ex vivo osteogenesis assays. DKK1-AS also reduced osteoclast numbers (p < 0.001), increased ß-catenin and T-cell factor 4 immunostaining reactivity (both p < 0.001), enhanced mineral apposition rate and bone formation rate per bone surface (both p < 0.001), and decreased osteoclast area (p < 0.001) in OI mice. DKK1-AS upregulated osteoprotegerin and downregulated nuclear factor-kappa B ligand transcription (both p < 0.001). Bone tissues from OI mice treated with DKK1-AS exhibited significantly higher breaking force compared to untreated OI mice (p < 0.001). CONCLUSIONS: Our study elucidates that DKK1-AS has the capability to enhance bone mechanical properties, restore the transcription of osteogenic genes, promote osteogenesis, and inhibit osteoclastogenesis in OI mice.

Therapeutic effects of extracorporeal shock wave therapy on patients with spastic cerebral palsy and Rett syndrome: clinical and ultrasonographic findings.

BACKGROUND: Extracorporeal shock wave therapy (ESWT) is reportedly effective for improving spasticity and motor function in children with cerebral palsy (CP). Because late-stage Rett syndrome has a similar presentation, this study aimed to investigate the effects of ESWT on these two diseases. MATERIAL AND METHODS: Patients diagnosed with spastic CP and Rett syndrome received 1500 impulses of ESWT at 4 Hz and 0.1 mJ/mm2, on their spastic legsonce weekly for a total of 12 weeks. Outcomes were assessed before and 4 and 12 weeks after ESWT. Clinical assessments included the Modified Ashworth Scale (MAS), passive range of motion (PROM), and Gross Motor Function Measure 88 (GMFM-88). Ultrasonographic assessments included muscle thickness, acoustic radiation force impulse (ARFI), and strain elastography. RESULTS: Fifteen patients with CP and six with Rett syndrome were enrolled in this study. After ESWT, patients with CP showed significant clinical improvement in the MAS (P = 0.011), ankle PROM (P = 0.002), walking/running/jumping function (P = 0.003), and total function (P < 0.001) of the GMFM-88. The patients with Rett syndrome showed improved MAS scores (P = 0.061) and significantly improved total gross motor function (P = 0.030). Under ARFI, patients with CP demonstrated decreased shear wave speed in the gastrocnemius medial head (P = 0.038). Conversely, patients with Rett syndrome show increased shear-wave speeds after ESWT. CONCLUSION: Our study provides evidence that a weekly course of low-dose ESWT for 12 weeks is beneficial for children with both CP and Rett syndrome, with the clinical effects of reducing spasticity and improving the gross motor function of the lower limbs. The ARFI sonoelastography reveals improvement of muscle stiffness in patients with CP after ESWT, but deteriorated in patients with Rett syndrome. The diverse therapeutic response to ESWT may be caused by the MECP2 mutation in Rett syndrome, having a continuous impact and driving the pathophysiology differently as compared to CP, which is secondary to a static insult. Trial registration IRB 201700462A3. Registered 22March 2017, https://cghhrpms.cgmh.org.tw/HRPMS/Default.aspx .

Clinical and radiologic outcomes of the modified phemister procedure with coracoclavicular ligament augmentation using mersilene tape versus hook plate fixation for acute acromioclavicular joint dislocation.

BACKGROUND: The clinical superiority of surgical treatment for acromioclavicular (AC) joint dislocation remains controversial. The aim of this study was to compare the clinical and radiological outcomes of the modified Phemister procedure with CC ligament augmentation using Mersilene tape to those of hook plate fixation for acute AC joint dislocation. METHODS: In this study, patients who received modified Phemister surgery with CC ligament augmentation using Mersilene tape (PM group) or hook plate fixation (HK group) for acute unstable AC joint dislocation with a minimum 5-year follow-up period were retrospectively reviewed. The clinical outcomes were evaluated according to blood loss during surgery, surgical duration, visual analogue scale (VAS), Constant-Murley score (CMS), University of California at Los Angeles (UCLA) shoulder rating scale, and the occurrence of complications. Radiological outcomes were assessed from radiographs according to multiple parameters, including CC distance maintenance, acromion osteolysis, and the presence of distal clavicle osteolysis. RESULTS: A total of 35 patients completed follow-up for more than 5 years and were analyzed in this study (mean = 74.08 months). There were 18 patients in the PM group and 17 in the HK group. The PM group exhibited similar improvement in functional outcome to the HK group. Regarding radiological outcomes, the HK group had a superior performance in terms of CC distance maintenance, of statistical significance (CCDR: 94.29 ± 7.01% versus 111.00 ± 7.69%, p < 0.001) after a one-year follow-up period. However, there were 4 cases of acromion osteolysis and 2 cases of distal clavicle osteolysis in the HK group. CONCLUSION: Hook plate fixation was found to be superior to the modified Phemister technique with CC ligament augmentation using Mersilene tape in terms of CC distance maintenance, but there was no significant difference in the functional outcome after 5 years of follow-up. Both surgical methods are reliable options for the treatment of acute AC joint dislocation. Modified Phemister surgery with CC ligament augmentation using Mersilene tape is a relatively lower-cost option for acute AC joint dislocation without the need of a second surgery for implant removal.

Treatment of sirolimus in the pathological femoral fracture related to blue rubber bleb nevus syndrome: A case report.

RATIONALE: Blue rubber bleb nevus syndrome (BRBNS) is a rare condition with characteristic vascular malformations of the skin, most frequently lesions of the gastrointestinal tract and central nervous system, and less often, the musculoskeletal system. We report a 5-year case of BRBNS complicated with pathological femoral fracture that was successfully treated with sirolimus. PATIENT CONCERNS: We report the case of a 1-week-old girl with a diagnosis of BRBNS who had multiple venous malformations over her body. She also presented with right lower-limb swelling and complicated with a pathological femoral fracture. DIAGNOSES: BRBNS with the complication of pathological femoral fracture. INTERVENTIONS: Treatment with low-dose sirolimus as an antiangiogenic agent was administered, combined with hip spica protection. OUTCOMES: The vascular lesion was reduced after about 6 months and the fracture site had healed around 2.5 years after initiation of sirolimus therapy. There were no drug adverse effects at the 5-year follow-up point. The patient showed excellent spirit and no obvious sequelae were found. LESSONS: To the best of our knowledge, this is the first report of the successful use of sirolimus in a patient with a pathological femoral fracture related to BRBNS complications.

The Risk of Bleeding and Adverse Events with Clopidogrel in Elective Hip and Knee Arthroplasty Patients.

Orthopedic surgeons often face a clinical dilemma on how to manage antiplatelet therapies during the time of surgery. This retrospective study is aimed to investigate the bleeding risk and adverse events in patients who hold or keep clopidogrel during elective major joints arthroplasty. Two hundred and ninety-six patients that were treated with clopidogrel while undergoing total hip or knee joint replacement between January 2009 and December 2018 were studied. Group 1 included 56 patients (18.9%) who kept using clopidogrel preoperatively. Group 2 included 240 patients who hold clopidogrel use ≥5 days preoperatively. Blood transfusion rates, estimated blood loss, complication rates, and adverse cardiocerebral events were collected and analyzed. The mean total blood loss was more in the group 1 patients as compared with that in the group 2 patients (1212.3 mL (685.8 to 2811.8) vs. 1068.9 mL (495.6 to 3294.3), p = 0.03). However, there was no significant difference between the two groups of patients regarding transfusion rates, bleeding-related complications, and infection rates. There was a trend toward a higher incidence of adverse cardiocerebral events in patients withholding clopidogrel for more than 5 days before surgery. The results of this study suggest that clopidogrel continuation could be safe and advisable for patients at thrombotic risk undergoing primary major joint replacement. Acute antiplatelet withdrawal for an extended period of time might be associated with an increased risk of postoperative thromboembolic events. More studies are required in the future to further prove this suggestion.

Outcome and Predictors of Septic Failure Following Total Joint Arthroplasty for Prior Septic Arthritis of Hip and Knee Joint.

BACKGROUND: Arthroplasty patients with prior septic arthritis are at a high risk of developing periprosthetic joint infection (PJI). The aims of this study are to investigate the outcome and predictors of septic failure following total joint arthroplasty (TJA) for prior septic arthritis. In addition, the optimal timing of TJA is also discussed. METHODS: A retrospective review of 105 TJA patients with prior septic arthritis between January 2000 and December 2019 was performed. Patient-specific and surgery-related factors, organism profiles, and other relevant variables were recorded. RESULTS: At a mean follow-up of 10.3 years, the PJI rate was 16.2%. The adjusted Cox proportional hazards model showed that male gender (HR, 9.95; P < .01), end-stage renal disease (HR, 37.34; P < .01), debridement surgery ≥3 times (HR,4.75; P = .04) and polymicrobial infection in primary septic arthritis (HR, 10.02; P = .02) were independent risk factors for PJI. Neither the types of initial debridement, nor one-stage vs two-stage arthroplasty was related to the risk of PJI. While delaying the timing of TJA did not correlate with a reduction of PJI rate, there was a higher risk of PJI re-infection by the same microorganisms isolated in prior septic arthritis if TJA was performed within 6 months after septic arthritis. CONCLUSIONS: Our study demonstrated that male gender, end-stage renal disease (ESRD), multiple debridement surgeries and polymicrobial septic arthritis predisposed septic failure of TJA following prior septic arthritis. Surgeons should counsel patients with the potential complications, and be cognizant about the risk factors pertaining to septic failure when considering TJA.

Pathological, Morphometric and Correlation Analysis of the Modified Mankin Score, Tidemark Roughness and Calcified Cartilage Thickness in Rat Knee Osteoarthritis after Extracorporeal Shockwave Therapy.

The paper displayed the pathological changes and relationships of the modified Mankin score, tidemark roughness and calcified cartilage (CC) thickness by extracorporeal shockwave therapy (ESWT) (0.25 mJ/ mm2 with 800 impulses) on different positions of the medial and lateral rat knee OA joint. After the experiments, the articular cartilage was assessed using histomorphometry, image analysis and statistical method. In the micro-CT analysis, ESWT on medial groups were better than lateral groups in the trabecular volume and trabecular number. The data showed a strong negative correlation between the modified Mankin score and tidemark roughness (r = -0.941; P < 0.001). In terms of the relationship of tidemark roughness with CC thickness, the medial and Sham groups showed a significant negative correlation (r = -0.788, P = 0.022). Additionally, the Euclidean distance derived from 3D scatter plot analysis was an indicator of chondropathic conditions, exhibiting a strong correlation with OA stage in the articular cartilage of the femur (r = 0.911, P < 0.001) and tibia (r = 0.890, P < 0.001) after ESWT. Principle component analysis (PCA) further demonstrated that ESWT applied to medial locations had a better outcome than treatment at lateral locations for knee OA by comparing with Sham and OA groups, and CC thickness was the most important factor affecting hyaline cartilage repair after ESWT.

Extracorporeal Shock Wave Therapy Combined with Platelet-Rich Plasma during Preventive and Therapeutic Stages of Intrauterine Adhesion in a Rat Model.

Intrauterine adhesion (IUA) is caused by artificial endometrial damage during intrauterine cavity surgery. The typical phenotype involves loss of spontaneous endometrium recovery and angiogenesis. Undesirable symptoms include abnormal menstruation and infertility; therefore, prevention and early treatment of IUA remain crucial issues. Extracorporeal shockwave therapy (ESWT) major proposed therapeutic mechanisms include neovascularization, tissue regeneration, and fibrosis. We examined the effects of ESWT and/or platelet-rich plasma (PRP) during preventive and therapeutic stages of IUA by inducing intrauterine mechanical injury in rats. PRP alone, or combined with ESWT, were detected an increased number of endometrial glands, elevated vascular endothelial growth factor protein expression (hematoxylin-eosin staining and immunohistochemistry), and reduced fibrosis rate (Masson trichrome staining). mRNA expression levels of nuclear factor-kappa B, tumor necrosis factor-α, transforming growth factor-ß, interleukin (IL)-6, collagen type I alpha 1, and fibronectin were reduced during two stages. However, PRP alone, or ESWT combined with PRP transplantation, not only increased the mRNA levels of vascular endothelial growth factor (VEGF) and progesterone receptor (PR) during the preventive stage but also increased PR, insulin-like growth factor 1 (IGF-1), and IL-4 during the therapeutic stage. These findings revealed that these two treatments inhibited endometrial fibrosis and inflammatory markers, thereby inhibiting the occurrence and development of intrauterine adhesions.

Piezoelectric Microvibration Mitigates Estrogen Loss-Induced Osteoporosis and Promotes Piezo1, MicroRNA-29a, and Wnt3a Signaling in Osteoblasts.

Biophysical stimulation alters bone-forming cell activity, bone formation and remodeling. The effect of piezoelectric microvibration stimulation (PMVS) intervention on osteoporosis development remains uncertain. We investigated whether 60 Hz, 120 Hz, and 180 Hz PMVS (0.05 g, 20 min/stimulation, 3 stimulations/week for 4 consecutive weeks) intervention affected bone integrity in ovariectomized (OVX) mice or osteoblastic activity. PMVS (120 Hz)-treated OVX mice developed fewer osteoporosis conditions, including bone mineral density loss and trabecular microstructure deterioration together with decreased serum resorption marker CTX-1 levels, as compared to control OVX animals. The biomechanical strength of skeletal tissue was improved upon 120 Hz PMVS intervention. This intervention compromised OVX-induced sparse trabecular bone morphology, osteoblast loss, osteoclast overburden, and osteoclast-promoting cytokine RANKL immunostaining and reversed osteoclast inhibitor OPG immunoreactivity. Osteoblasts in OVX mice upon PMVS intervention showed strong Wnt3a immunoreaction and weak Wnt inhibitor Dkk1 immunostaining. In vitro, PMVS reversed OVX-induced loss in von Kossa-stained mineralized nodule formation, Runx2, and osteocalcin expression in primary bone-marrow stromal cells. PMVS also promoted mechanoreceptor Piezo1 expression together with increased microRNA-29a and Wnt3a expression, whereas Dkk1 rather than SOST expression was repressed in MC3T3-E1 osteoblasts. Taken together, PMVS intervention promoted Piezo1, miR-29a, and Wnt signaling to upregulate osteogenic activity and repressed osteoclastic bone resorption, delaying estrogen deficiency-induced loss in bone mass and microstructure. This study highlights a new biophysical remedy for osteoporosis.

Combined Melatonin and Extracorporeal Shock Wave Therapy Enhances Podocyte Protection and Ameliorates Kidney Function in a Diabetic Nephropathy Rat Model.

(1) Background: Diabetic nephropathy (DN) is common complication of diabetes. Current therapy for DN does not include promotion of podocyte protection. Therefore, we investigated the therapeutic effect of melatonin (Mel) combined extracorporeal shock wave (SW) therapy on a DN rat model. (2) Methods: The DN rats were treated with Mel (5 mg/kg) twice a week for 6 weeks and SW treatment once a week (0.13 mJ/mm2) for 6 weeks. We assessed urine microalbumin, albumin to creatinine ratio (ACR), glomerular hypertrophy, glomerular fibrosis, podocyte markers (Wilm's tumor protein-1, synaptopodin and nephrin), cell proliferation, cell survival, cell apoptosis, renal inflammation and renal oxidative stress. (3) Results: The Mel combined SW therapy regimen significantly reduced urine microalbumin excretion (3.3 ± 0.5 mg/dL, p < 0.001), ACR (65.2 ± 8.3 mg/g, p < 0.001), glomerular hypertrophy (3.1 ± 0.1 × 106 µm3, p < 0.01) and glomerular fibrosis (0.9 ± 0.4 relative mRNA fold, p < 0.05). Moreover, the Mel combined SW therapy regimen significantly increased podocyte number (44.1 ± 5.0% area of synaptopodin, p < 0.001) in the Mel combined SW group. This is likely primarily because Mel combined with SW therapy significantly reduced renal inflammation (753 ± 46 pg/mg, p < 0.01), renal oxidative stress (0.6 ± 0.04 relative density, p < 0.05), and apoptosis (0.3 ± 0.03 relative density, p < 0.001), and also significantly increased cell proliferation (2.0 ± 0.2% area proliferating cell nuclear antigen (PCNA), p < 0.01), cell survival, and nephrin level (4.2 ± 0.4 ng/mL, p < 0.001). (4) Conclusions: Mel combined SW therapy enhances podocyte protection and ameliorates kidney function in a DN rat model. Mel combined SW therapy may serve as a novel noninvasive and effective treatment of DN.

Autologous Adipose-Derived Mesenchymal Stem Cells Combined with Shockwave Therapy Synergistically Ameliorates the Osteoarthritic Pathological Factors in Knee Joint.

Adipose-derived mesenchymal stem cells (ADSCs) and shockwave (SW) therapy have been shown to exert a chondroprotective effect for osteoarthritis (OA). The results of this study demonstrated that autologous ADSCs had dose-dependent and synergistic effects with SW therapy (0.25 mJ/mm2 with 800 impulses) in OA rat knee joint. Autologous, high-dose 2 × 106 ADSCs (ADSC2 group) combined with SW therapy significantly increased the bone volume, trabecular thickness, and trabecular number among in the treatment groups. ADSC2 combined with SW therapy significantly reduced the synovitis score and OARSI score in comparison with other treatments. In the analysis of inflammation-induced extracellular matrix factors of the articular cartilage in OA, the results displayed that ADSC2 combined with SW therapy had a greater than other treatments in terms of reducing tumor necrosis factor-inducible gene (TSG)-6 and proteoglycan (PRG)-4, in addition to increasing tissue inhibitor matrix metalloproteinase (TIMP)-1 and type II collagen. Furthermore, ADSC2 combined with SW therapy significantly reduced the expression of inflammation-induced bone morphogenetic protein (BMP)-2 and BMP-6. Therefore, the results demonstrated that ADSC2 combined with SW therapy had a synergistic effect to ameliorate osteoarthritic pathological factors in OA joints.

Systemic effects of platelet-rich plasma local injection on serum and urinary anabolic metabolites: A prospective randomized study.

Platelet-rich plasma (PRP) is widely utilized in the treatment of sports injuries. However, potential systemic effects after localized PRP injection are unclear at present. In this prospective randomized study, 24 Taiwanese male athletes with tendinopathy were randomized into a PRP group (n = 13) or a saline group (n = 11). The concentrations of serum and urine biomarkers were quantified by enzyme-linked immunosorbent assay assessment as well as gas chromatographic and mass spectrometric analysis, respectively. The results showed no significant differences in serum levels of growth hormone, insulin-like growth factor-1, insulin-like growth factor-binding protein 3, vascular endothelial growth factor, platelet-derived growth factor-BB, or serum substance P(SP) between the two groups before intervention, nor at 1, 2, or 7 days after intervention. However, a significant decrease in the serum SP level 1 and 7 days after PRP injection was observed. Regarding urinary concentrations of metabolites of anabolic androgenic steroids (AAS), no between-group differences before intervention, nor at 1, 2, or 7 days after intervention, were observed. Our study failed to observe significant surge of serum anabolic molecules and urinary excretion of anabolic AAS metabolites after PRP injection.

The effects of immediate programmed cryotherapy and continuous passive motion in patients after computer-assisted total knee arthroplasty: a prospective, randomized controlled trial.

BACKGROUND: The postoperative nursing intervention with immediate cryotherapy and continuous passive motion (CPM) remains elusive regarding the postoperative pain and range of motion (ROM) for patients undergoing computer-assisted total knee arthroplasty (CAS-TKA). METHODS: A prospective, randomized controlled trial with a purposive sampling method was utilized. Sixty patients scheduled for a unilateral CAS-TKA at a medical center were randomly assigned to the intervention group (n = 30) and control group (n = 30). The intervention group applied programed cryotherapy and CPM within 1 h while returning to the ward on the day of surgery, while the control group did not. Data were analyzed using mixed models to compare the numeric rating scale (NRS) for pain, ROM, and swelling at postoperative day (POD) 4. RESULTS: There was no significant difference in the NRS score between the groups (p = 0.168). The intervention group had significantly higher ROM than the control group (98° vs. 91°, p = 0.004) at POD 4. Although no significant difference in joint swelling was found between groups (p = 0.157), the intervention group had lower mean joint swelling (32.2 cm) than the control group (33.9 cm). CONCLUSIONS: Immediate programmed cryotherapy and continuous passive motion could help to improve ROM quickly after CAS-TKA. It should be incorporated into the daily nursing plan for patients undergoing CAS-TKA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04136431 . Registered 23 October 2019-retrospectively registered.

Bromodomain Protein BRD4 Accelerates Glucocorticoid Dysregulation of Bone Mass and Marrow Adiposis by Modulating H3K9 and Foxp1.

Glucocorticoid provokes bone mass loss and fatty marrow, accelerating osteoporosis development. Bromodomain protein BRD4, an acetyl-histone-binding chromatin reader, regulates stem cell and tissue homeostasis. We uncovered that glucocorticoid inhibited acetyl Lys-9 at the histone 3 (H3K9ac)-binding Runx2 promoter and decreased osteogenic differentiation, whereas bromodomain protein 4 (BRD4) and adipocyte formation were upregulated in bone-marrow mesenchymal progenitor cells. BRD4 knockdown improved H3K9ac occupation at the Runx2 promoter and osteogenesis, but attenuated glucocorticoid-mediated adipocyte formation together with the unaffected H3K9ac-binding PPARγ2 promoter. BRD4 regulated epigenome related to fatty acid metabolism and the forkhead box P1 (Foxp1) pathway, which occupied the PPARγ2 promoter to modulate glucocorticoid-induced adipocytic activity. In vivo, BRD4 inhibitor JQ-1 treatment mitigated methylprednisolone-induced suppression of bone mass, trabecular microstructure, mineral acquisition, and osteogenic differentiation. Foxp1 signaling, marrow fat, and adipocyte formation in glucocorticoid-treated skeleton were reversed upon JQ-1 treatment. Taken together, glucocorticoid-induced H3K9 hypoacetylation augmented BRD4 action to Foxp1, which steered mesenchymal progenitor cells toward adipocytes at the cost of osteogenic differentiation in osteoporotic skeletons. BRD4 inhibition slowed bone mass loss and marrow adiposity. Collective investigations convey a new epigenetic insight into acetyl histone reader BRD4 control of osteogenesis and adipogenesis in skeleton, and highlight the remedial effects of the BRD4 inhibitor on glucocorticoid-induced osteoporosis.

The Epidemiology of Hip Fracture among Subjects with Pyogenic Liver Abscess (PLA): A Nationwide Population-Based Study.

Pyogenic liver abscess (PLA) is a potentially fatal disease that can stimulate prominent systemic inflammation. Osteoporotic hip fracture is a major complication of systemic inflammation. This study tried to determine the epidemiology of hip fractures among PLA patients. All subjects admitted due to PLA during 1999∼2010 were assessed, excluding the subjects with a history of high energy trauma, malignancy, and previous hip fracture. We matched the control subjects to PLA patients according to age, gender, and the coding of osteoporosis by 1 : 4 ratio. The PLA patients had a 1.17-fold risk of hip fracture than the controls (aHR = 1.17, 95% CI = 1.07-1.29) after adjusting for gender, age, and comorbidities. Considering death as the competing event of suicide, the PLA patients had 1.10-fold suicide risk (aHR = 1.10, 95% CI: 1.00-1.21) than the control subjects under the competing risks regression model. The cumulative incidence of hip fracture was higher in the PLA cohort (log-rank test, p < 0.001). When compared to the controls, the fracture risk was 18.4-fold (aHR = 18.4, 95% CI = 13.0-26.1) for the PLA patients admitted 2-3 times per year and 46.0-fold (aHR = 46.0, 95% CI = 31.2-67.8) for the PLA patients admitted ≧4 times per year. The impact of PLA is more prominent among the subjects aged <45 years (aHR = 2.81, 95% CI = 1.42-5.56). Preventive measures for hip fracture might be warranted for PLA patients.

Shockwave Therapy Combined with Autologous Adipose-Derived Mesenchymal Stem Cells Is Better than with Human Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells on Knee Osteoarthritis.

Extracorporeal shockwave therapy (ESWT) and mesenchymal stem cells (MSCs) have been reported to have chondroprotective effects in knee osteoarthritis (OA). Here, we examined whether autologous adipose-derived mesenchymal stem cells (ADMSCs) and human umbilical cord Wharton's jelly-derived mesenchymal stem cells (WJMSCs) increased the efficacy of ESWT in knee OA, and compared the efficacy of the two. The treatment groups exhibited significant improvement of knee OA according to pathological analysis, micro-computed tomography (CT), and immunohistochemistry (IHC) staining. The ADMSCs and ESWT+ADMSCs groups exhibited increased trabecular thickness and bone volume as compared with the ESWT, WJMSCs, and ESWT+WJMSCs groups individually. According to the results of IHC staining, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) activity and caspase-3 were significantly reduced in the ADMSCs and ESWT+ADMSCs groups as compared with the WJMSCs and ESWT+WJMSC groups. In mechanistic factor analysis, the synergistic effect of ESWT+ADMSCs was observed as being greater than the efficacies of other treatments in terms of expressions of transforming growth factor (TGF)-ß, runt-related transcription factor (RUNX)-2 and sex determining region Y-box (SOX)-9. The type II collagen was expressed at a higher level in the WJMSCs group than in the others. Furthermore, ESWT+ADMSCs reduced the expression of platelet-derived growth factor (PDGF)-BB and increased the expression of bone morphogenetic protein (BMP)-4. Therefore, we demonstrated that ESWT+ADMSCs had a synergistic effect greater than that of ESWT+WJMSCs for the treatment of early knee OA.

Use of Antimicrobial-Impregnated Incise Drapes to Prevent Periprosthetic Joint Infection in Primary Total Joint Arthroplasty: A Retrospective Analysis of 9774 Cases.

BACKGROUND: Antimicrobial-impregnated incise drapes are often used despite any literature that demonstrates a reduction in the rate of periprosthetic joint infection (PJI). The aim of this study is to compare the efficacy of antimicrobial-impregnated incise drapes with nonantimicrobial-impregnated incise drapes for the prevention of PJI in patients undergoing total joint arthroplasty (TJA). METHODS: A retrospective study of 9774 primary TJAs from 2000 to 2012 was performed. Patients who received an antimicrobial-impregnated incise drape (n = 5241) were compared with patients who received a nonantimicrobial-impregnated incise drape (n = 4533). The decision to use an antimicrobial drape was based on the surgeon's discretion. Patients who developed PJI within 1 year after index surgery were identified. Multivariate logistic regression analysis and sensitivity analysis using propensity score matching were performed to control for potential confounders. RESULTS: The overall PJI rate was 1.14% (60 of 5241) for patients who received an antimicrobial-impregnated incise drape compared with 1.26% (57 of 4533) for those with a nonantimicrobial-impregnated incise drape. There was no difference in the PJI rate between patients with an antimicrobial-impregnated incise drape and those who received nonantimicrobial-impregnated incise drape in the univariate (odds ratio [OR] = 0.91; 95% confidence interval [CI] = 0.63-1.30), multivariate (adjusted OR = 0.92; 95% CI, 0.63-1.34), or propensity score matching analysis (OR = 0.84; 95% CI = 0.52-1.35). CONCLUSION: Despite the increasing adoption of the use of antimicrobial-impregnated incise drapes in our institute, this study suggests that antimicrobial-impregnated incise drapes do not reduce PJI in patients undergoing primary TJAs.

Extended Postoperative Prophylactic Antibiotics with First-Generation Cephalosporin Do Not Reduce the Risk of Periprosthetic Joint Infection following Aseptic Revision Total Knee Arthroplasty.

Postoperative prophylactic antibiotics administered within 24 hours of primary total knee arthroplasty (TKA) have been documented to prevent periprosthetic joint infection (PJI). However, the effectiveness of this regimen is still unclear in aseptic revision TKA. The purpose of this study was to evaluate whether extended postoperative prophylactic antibiotics would reduce the PJI rate compared with the current 24-hour standard postoperative prophylactic antibiotics after aseptic revision TKA. A retrospective review of 236 patients (46 men, 190 women, 252 knees) who underwent aseptic revision TKA between 2005 and 2013 was conducted. Patients who underwent septic revision, had a positive intraoperative culture, or who had less than 2 years of follow-up were excluded. Patients were divided according to the duration of postoperative prophylactic antibiotics to standard group (76 knees, ≤ 24 hours) or extended group (176 knees, > 24 hours). PJI was determined by the Musculoskeletal Infection Society criteria. A multivariate Cox proportional hazards regression analysis was performed. The mean follow-up was 5.2 ± 2.5 years. Patients with extended postoperative prophylactic antibiotics had a lower PJI rate (1.1%) compared with standard group (3.9%), but the difference was not statistically significant (p = 0.14). Body mass index ≥ 30 kg/m2 was the only independent risk factor of PJI (adjusted hazard ratio [HR]: 9.59; 95% confidence interval [CI]: 1.07-86.04, p = 0.043). The use of extended postoperative prophylactic antibiotics was not a risk factor for PJI (adjusted HR: 0.34; 95% CI: 0.06-2.04, p = 0.238). After 10 years, the two groups had similar infection-free implant survival rate (95.9 vs. 98.9%, p = 0.15). Our findings demonstrate that extended postoperative prophylactic antibiotics did not reduce PJI rate compared with the standard group in aseptic revision TKA. A further prospective, randomized study with a standardized postoperative antibiotic protocol is necessary to address this topic. Level of evidence is prognostic Level III.

Tranexamic Acid Reduces Total Blood Loss and Inflammatory Response in Computer-Assisted Navigation Total Knee Arthroplasty.

INTRODUCTION: Tranexamic acid (TXA) is an effective blood salvage agent that reduces perioperative blood loss in conventional total knee arthroplasty (TKA). As computer-assisted surgery for TKA (CAS-TKA) results in a lower perioperative blood loss than conventional TKA, the additional effect of blood conservation by TXA might be mitigated. This study aimed to evaluate the efficacy of TXA in CAS-TKA. METHODS: We retrospectively reviewed 222 consecutive patients who underwent CAS-TKA. Intravenous TXA was administered in 103 patients (TXA group) at a dosage of 20 mg/kg 15 min before deflation of the tourniquet. The other 119 patients did not receive TXA (control group). Patient demographic data including age, gender, BMI, DM, and hypertension were collected. The primary outcomes were the estimated total blood loss (ETBL) and perioperative data, including tourniquet duration, preoperative and postoperative day 1 (POD1) and day 3 (POD3) serum D-dimer, CRP, hemoglobin (Hb), and hematocrit (Hct) levels. Secondary outcomes including transfusion rate and 90-day complications were recorded. RESULTS: The ETBL was lower in the TXA group on both POD1 (404.34 ± 234.77 vs. 595.47 ± 279.04, p < 0.001) and POD3 (761.39 ± 260.88 vs. 987.79 ± 326.58, p < 0.001). The TXA group also demonstrated a lower level of CRP on POD1 (p=0.02) and lower levels of CRP and serum D-dimer on POD3 (p=0.008 and p < 0.001). Consumption of fibrinogen was higher in the control group on both POD1 (p=0.013) and POD3 (p < 0.001). Length of hospital stay was lower in the TXA group (5.42 ± 1.21 vs. 6.25 ± 1.49, p < 0.001). The transfusion rate and perioperative complications were not significantly different between the two groups. CONCLUSION: Administration of TXA is not only effective in reducing perioperative blood loss and length of hospital stay but also exerts an anti-inflammatory effect following CAS-TKA without causing major complications.

Effects of computer-assisted navigation versus the conventional technique for total knee arthroplasty on levels of plasma thrombotic markers: a prospective study.

BACKGROUND: Venous thromboembolism (VTE) is a major sequela after total knee arthroplasty (TKA). We prospectively compared the differences in the perioperative plasma D-dimer and fibrinogen levels between the individuals undergoing TKA via computer-assisted navigation and via a conventional method as the surrogate comparison for VTE. There were 174 patients fulfilling the inclusion criteria and providing valid informed consent between September 2011 and November 2013. There were 69 females and 20 males in the navigation-assisted group (median age: 71.00 years), while the conventional group was composed of 59 females and 26 males (median age: 69.00 years). Blood samples were obtained prior to and at 24 and 72 h after surgery for measurement of the levels of plasma D-dimer and fibrinogen. RESULTS: A significantly lower plasma D-dimer level 24 h after TKA (p = 0.001) and a milder postoperative surge 24 h after TKA (p = 0.002) were observed in patients undergoing navigation-assisted TKA. The proportions of subjects exceeding the plasma D-dimer cut-off values of 7.5, 8.6 and 10 mg/L 24 h after TKA were all significantly higher in the conventional group than in the navigation-assisted group (p = 0.024, 0.004, and 0.004, respectively). CONCLUSIONS: A lower plasma D-dimer level and a milder surge in the plasma D-dimer level were observed in patients undergoing navigation-assisted TKA in comparison with patients undergoing conventional TKA 24 h after surgery. These findings may supplement the known advantages of navigation-assisted TKA.