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 .

Effects of Adding Extracorporeal Shockwave Therapy (ESWT) to Platelet-Rich Plasma (PRP) among Patients with Rotator Cuff Partial Tear: A Prospective Randomized Comparative Study.

A rotator cuff tear is a prevalent ailment affecting the shoulder joint. The clinical efficacy of combined therapy remains uncertain for partial rotator cuff tears. In this study, we integrated extracorporeal shockwave therapy (ESWT) with platelet-rich plasma (PRP) injection, juxtaposed with PRP in isolation. Both cohorts exhibited significant improvements in visual analogue scale (VAS), Constant-Murley score (CMS), degrees of forward flexion, abduction, internal rotation, and external rotation, and the sum of range of motion (SROM) over the six-month assessment period. The application of ESWT in conjunction with PRP exhibited notable additional enhancements in both forward flexion (p = 0.033) and abduction (p = 0.015) after one month. Furthermore, a substantial augmentation in the range of shoulder motion (SROM) (p < 0.001) was observed after six months. We employed isobaric tag for relative and absolute quantitation (iTRAQ) to analyze the differential plasma protein expression in serum samples procured from the two groups after one month. The concentrations of S100A8 (p = 0.042) and S100A9 (p = 0.034), known to modulate local inflammation, were both lower in the ESWT + PRP cohort. These findings not only underscore the advantages of combined therapy but also illuminate the associated molecular changes.

Changes in Serum Bone Metabolism Markers after Living Donor Liver Transplantation (LDLT) and Their Association with Fracture Occurrences.

Living donor liver transplantation (LDLT) is lifesaving, but can lead to osteoporosis and fractures. In our 3-year study of 25 LDLT recipients, we observed significant reductions in lumbar spine and femoral neck T scores, along with bone resorption marker reductions and liver regeneration marker increases. Serum calcium levels increased, while osteoprotegerin (OPG) decreased and Dickkopf-related protein 1 (DKK-1) increased. Patients who suffered fractures within 3 years of LDLT had higher serum OPG, lower serum nuclear factor kappa B ligand (RANKL), a higher OPG/RANKL ratio and higher serum DKK-1 levels. OPG, RANKL, OPG/RANKL ratio and DKK-1 levels before LDLT predicted hip or spine fractures within three years after LDLT. Further research is necessary to determine the optimal level of osteoclastic activity for preventing fracture onset.

Cartilage-specific knockout of miRNA-128a expression normalizes the expression of circadian clock genes (CCGs) and mitigates the severity of osteoarthritis.

BACKGROUND: Micro-ribonucleic acids (miRNAs) are involved in osteoarthritis (OA) pathogenesis and clock-controlled genes (CCGs) regulation. However, the interaction between miRNAs and CCGs remains unclear. METHODS: Human OA samples were used to assess CCGs expression. Cartilage-specific miR-128a knockout mouse model was established to investigate miR-128a's role in OA pathogenesis. Destabilization of the medial meniscus (DMM) model was employed to simulate OA. RESULTS: Transcription levels of nuclear receptor subfamily 1 group D member 2 (NR1D2) were lower in both human OA samples and wild-type mice undergoing DMM compared to non-OA counterparts. MiR-128a knockout mice showed reduced disturbances in micro-computed tomographic and kinematic parameters following DMM, as well as less severe histologic cartilage loss. Immunohistochemistry staining revealed a lesser decrease in NR1D2-positive chondrocytes after DMM in miR-128a knockout mice than in wild-type mice. NR1D2 agonist rescued the suppressed expression of cartilage anabolic factors and extracellular matrix deposition caused by miR-128a precursor. CONCLUSIONS: Cartilage-specific miR-128a knockout mice exhibited reduced severity, less disrupted kinematic parameters, and suppressed NR1D2 expression after DMM. NR1D2 enhanced the expression of cartilage anabolic factors and extracellular matrix deposition. These findings highlight the potential of employing miR-128a and CCG-targeted therapy for knee OA.

Inhibition of histone lysine demethylase 6A promotes chondrocytic activity and attenuates osteoarthritis development through repressing H3K27me3 enhancement of Wnt10a.

Histone hypermethylation represses gene transcription, which affects cartilage homeostasis or joint remodeling. Trimethylation of lysine 27 of histone 3 (H3K27me3) changes epigenome signatures, regulating tissue metabolism. This study aimed to investigate whether loss of H3K27me3 demethylase Kdm6a function affected osteoarthritis development. We revealed that chondrocyte-specific Kdm6a knockout mice developed relatively long femurs and tibiae as compared to wild-type mice. Kdm6a deletion mitigated osteoarthritis symptoms, including articular cartilage loss, osteophyte formation, subchondral trabecular bone loss, and irregular walking patterns of destabilized medial meniscus-injured knees. In vitro, loss of Kdm6a function compromised the loss in expression of key chondrocyte markers Sox9, collagen II, and aggrecan and improved glycosaminoglycan production in inflamed chondrocytes. RNA sequencing showed that Kdm6a loss changed transcriptomic profiles, which contributed to histone signaling, NADPH oxidase, Wnt signaling, extracellular matrix, and cartilage development in articular cartilage. Chromatin immunoprecipitation sequencing uncovered that Kdm6a knockout affected H3K27me3 binding epigenome, repressing Wnt10a and Fzd10 transcription. Wnt10a was, among others, functional molecules regulated by Kdm6a. Forced Wnt10a expression attenuated Kdm6a deletion-induced glycosaminoglycan overproduction. Intra-articular administration with Kdm6a inhibitor GSK-J4 attenuated articular cartilage erosion, synovitis, and osteophyte formation, improving gait profiles of injured joints. In conclusion, Kdm6a loss promoted transcriptomic landscapes contributing to extracellular matrix synthesis and compromised epigenetic H3K27me3-mediated promotion of Wnt10a signaling, preserving chondrocytic activity to attenuate osteoarthritic degeneration. We highlighted the chondroprotective effects of Kdm6a inhibitor for mitigating the development of osteoarthritic disorders.

Micro Ribonucleic Acid-29a (miR-29a) Antagonist Normalizes Bone Metabolism in Osteogenesis Imperfecta (OI) Mice Model.

Osteogenesis imperfecta (OI) is not curative nowadays. This study tried to unriddle the therapeutic potential of micro ribonucleic acid-29a (miR-29a) antagonist in treating OI in a mouse animal model (B6C3Fe a/a-Col1a2oim/J). We showed that the expression levels of miR-29a were higher in bone tissues obtained from the OI mice than from wild-type mice demonstrated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization assay. We established lentivirus-shuttled vector expressing miR-29a antisense oligonucleotide (miR-29a-AS) and miR-29a precursors (pre-miR-29a), showing that the inferior bony architecture in micro-computed tomography and pertinent morphometric parameters could be rescued by miR-29a-AS and deteriorated by pre-miR-29a. The decreased proliferating cell nuclear antigen (PCNA), increased Dickkopf-1 (DKK1), and decreased ß-catenin expression in OI mice could be accentuated by pre-miR-29a and normalized by miR-29a-AS. The decreased osteogenesis and increased osteoclastogenesis in OI mice could also be accentuated by pre-miR-29a and normalized by miR-29a-AS. miR-29a-AS did not seem to possess severe hepatic or renal toxicities.

The Differential Systemic Biological Effects between Computer Navigation and Conventional Total Knee Arthroplasty (TKA) Surgeries: A Prospective Study.

Distal femur reaming-free total knee arthroplasty (TKA) was reported to possess lower risk of acute myocardial infarction (AMI) or venous thromboembolism (VTE) than conventional TKA in a retrospective population-based study. We tried to offer prospective biological evidence by comparing the levels of AMI and VTE serum surrogate markers among the patients undertaking navigation and conventional TKAs to support these observations. Thirty-four participants undertaking navigation TKA and 34 patients receiving conventional TKA were recruited between February 2013 and December 2015. Blood samples were drawn from all participants before TKA, and 24 and 72 h after TKA, to assess the concentration of soluble P-selectin, matrix metalloproteinase-9 (MMP-9), C-reactive protein (CRP), and interleukin-8 (IL-8) between the participants undergoing navigation and conventional TKAs. We showed that significantly lower serum levels of soluble P-selectin 24 h after, as well as CRP 24 and 72 h after TKA could be observed in the navigation cohort. The more prominent surge of serum soluble P-selectin and CRP were perceived 24 and 72 h after TKA among the participants undergoing conventional TKA. Based upon our prospective biological evidence, the merits of navigation TKA are strengthened by lower levels of AMI and VTE serum surrogate markers.

The Antagonism of Neuropeptide Y Type I Receptor (Y1R) Reserves the Viability of Bone Marrow Stromal Cells in the Milieu of Osteonecrosis of Femoral Head (ONFH).

Neuropeptide Y (NPY)-Y1 receptor (Y1R) signaling is known to negatively affect bone anabolism. Our study aimed at investigating the impact of NPY-Y1R signaling in the pathogenesis of glucocorticoid-related osteonecrosis of the femoral head (ONFH). Femoral heads were retrieved from 20 patients with and without ONFH, respectively. The bone marrow stromal cells (BMSCs) from ONFH femoral heads were treated with Y1R agonists and antagonists for subsequent analysis. We showed that the local NPY expression level was lower in ONFH heads. The Y1R agonists and antagonists disturb and facilitate the survival of BMSCs. The transcription of stromal derived factor-1 (SDF-1) was enhanced by Y1R antagonists. Our study showed that the local NPY expression level was lower in ONFH heads. Y1R antagonists facilitate the survival of BMSCs and stimulate the transcription of SDF-1 by BMSCs. These findings shed light on the role of NPY-Y1R signaling in the pathogenesis of ONFH.

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.

Decreased Expression of Leptin among Patients with Shoulder Stiffness.

Shoulder stiffness (SS) is a disease that is fibroblastic and inflammatory in nature. Leptin is an adipokine-mediating the fibroblastic and inflammatory processes of various diseases. Our study tried to investigate the role of leptin in SS pathogenesis. Subacromial bursa from stiff and non-stiff shoulders were obtained for reverse transcription-polymerase chain reaction (RT-PCR) analysis and immunoblotting. Subacromial fluid was obtained for enzyme-linked immunosorbent assay. We showed that the expression level of leptin was lower in the subacromial bursae from the stiff shoulders in RT-PCR analysis (p < 0.001) and immunoblotting (p < 0.001). The concentration of leptin was also lower in the subacromial fluid derived from stiff shoulders. The leptin level in the subacromial fluid was positively associated with the constant score, total range of motion, flexion, abduction, and external rotation. The synovial fibroblasts derived from stiff shoulder-retrieved subacromial bursa were treated by 0, 1, and 3 µM leptin. Under RT-qPCR analysis, leptin was shown to dose-dependently decrease the transcription of IL-6, IL-10, and IL-13, but without impact on IL-1ß and IL-4 (p < 0.001, p = 0.001, p = 0.001, p = 0.137, and p = 0.883 by ANOVA test, respectively). These results shed light on the role of leptin in orchestrating the disease processes of SS.

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.

Histone H3K27 demethylase UTX compromises articular chondrocyte anabolism and aggravates osteoarthritic degeneration.

Epigenome alteration in chondrocytes correlates with osteoarthritis (OA) development. H3K27me3 demethylase UTX regulates tissue homeostasis and deterioration, while its role was not yet studied in articulating joint tissue in situ. We now uncovered that increased UTX and H3K27me3 expression in articular chondrocytes positively correlated with human knee OA. Forced UTX expression upregulated the H3K27me3 enrichment at transcription factor Sox9 promoter, inhibiting key extracellular matrix molecules collagen II, aggrecan, and glycosaminoglycan in articular chondrocytes. Utx overexpression in knee joints aggravated the signs of OA, including articular cartilage damage, synovitis, osteophyte formation, and subchondral bone loss in mice. Chondrocyte-specific Utx knockout mice developed thicker articular cartilage than wild-type mice and showed few gonarthrotic symptoms during destabilized medial meniscus- and collagenase-induced joint injury. In vitro, Utx loss changed H3K27me3-binding epigenomic landscapes, which contributed to mitochondrial activity, cellular senescence, and cartilage development. Insulin-like growth factor 2 (Igf2) and polycomb repressive complex 2 (PRC2) core components Eed and Suz12 were, among others, functional target genes of Utx. Specifically, Utx deletion promoted Tfam transcription, mitochondrial respiration, ATP production and Igf2 transcription but inhibited Eed and Suz12 expression. Igf2 blockade or forced Eed or Suz12 expression increased H3K27 trimethylation and H3K27me3 enrichment at Sox9 promoter, compromising Utx loss-induced extracellular matrix overproduction. Taken together, UTX repressed articular chondrocytic activity, accelerating cartilage loss during OA. Utx loss promoted cartilage integrity through epigenetic stimulation of mitochondrial biogenesis and Igf2 transcription. This study highlighted a novel noncanonical role of Utx, in concert with PRC2 core components, in controlling H3K27 trimethylation and articular chondrocyte anabolism and OA development.

Gut Microbiota Ecosystem Governance of Host Inflammation, Mitochondrial Respiration and Skeletal Homeostasis.

Osteoporosis and osteoarthritis account for the leading causes of musculoskeletal dysfunction in older adults. Senescent chondrocyte overburden, inflammation, oxidative stress, subcellular organelle dysfunction, and genomic instability are prominent features of these age-mediated skeletal diseases. Age-related intestinal disorders and gut dysbiosis contribute to host tissue inflammation and oxidative stress by affecting host immune responses and cell metabolism. Dysregulation of gut microflora correlates with development of osteoarthritis and osteoporosis in humans and rodents. Intestinal microorganisms produce metabolites, including short-chain fatty acids, bile acids, trimethylamine N-oxide, and liposaccharides, affecting mitochondrial function, metabolism, biogenesis, autophagy, and redox reactions in chondrocytes and bone cells to regulate joint and bone tissue homeostasis. Modulating the abundance of Lactobacillus and Bifidobacterium, or the ratio of Firmicutes and Bacteroidetes, in the gut microenvironment by probiotics or fecal microbiota transplantation is advantageous to suppress age-induced chronic inflammation and oxidative damage in musculoskeletal tissue. Supplementation with gut microbiota-derived metabolites potentially slows down development of osteoarthritis and osteoporosis. This review provides latest molecular and cellular insights into the biological significance of gut microorganisms and primary and secondary metabolites important to cartilage and bone integrity. It further highlights treatment options with probiotics or metabolites for modulating the progression of these two common skeletal disorders.

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.

Are Risk Factors for Postoperative Significant Hemorrhage following Total Knee Arthroplasty Potentially Modifiable? A Retrospective Cohort Study.

Total knee arthroplasty (TKA) is the treatment of choice for end-stage osteoarthritis (OA) of the knee, because it alleviates pain and restores function of the knee. However, TKA-associated hemorrhage and subsequent anemia remain a concern. Most previous studies have defined meaningful postoperative bleeding as blood loss > 500 mL or hemoglobin (Hb) drop > 20 g/L. Therefore, we defined significant hemorrhage as a postoperative Hb drop more than 20 g/L in this study, and we investigated possible risk factors related to significant hemorrhage in TKA and whether these risk factors are modifiable. This retrospective study was conducted through a comprehensive review of the perioperative records of patients with OA of the knee who underwent TKA between January 2009 and December 2015 at our hospital. Patients were allocated into two groups: patients in Group A had their Hb drop ≤ 20 g/L; patients in Group B had their Hb drop > 20 g/L. Factors analyzed included sex, age, body mass index (BMI), the American Society of Anesthesiologists (ASA) classification, comorbidities, preoperative platelet count, use of tranexamic acid (TXA), operation time, and type of anesthesia. A total of 3350 patients met the criteria for analysis, with 1782 patients allocated to Group A and 1568 patients to Group B. Five independent risk factors for significant hemorrhage were identified: male sex (odds ratio(OR), 1.29; 95% confidence interval(CI), 1.08−1.53; p = 0.005), age (OR, 1.02; 95% CI, 1.01−1.03; p = 0.001), use of TXA (OR, 0.39; 95% CI, 0.34−0.45; p < 0.001), spinal anesthesia versus general anesthesia (OR, 0.71; 95% CI, 0.56−0.90; p = 0.004), and preoperative platelet count (OR, 0.96; 95% CI, 0.93−0.98; p = 0.001). Of these identified risk factors, preoperative platelet count, use of TXA, and spinal anesthesia are modifiable. These potentially modifiable risk factors need to be taken into consideration when making both the perioperative care and anesthesia plan by surgeons and anesthesiologists, especially in patients at risk of significant hemorrhage.

Avoidance of intramedullary violation in computer-assisted total knee arthroplasty lowers the incidence of periprosthetic joint infection compared with conventional total knee arthroplasty: A propensity score matching analysis of 5342 cases.

BACKGROUND: Conventional total knee arthroplasty (CONV-TKA) inevitably perturbs femoral medullary canal, disturbs medullary micro-architecture and increases blood loss and inflammatory responses. We hypothesized that avoidance of intramedullary violation may lower the incidence of periprosthetic joint infection (PJI). The aim of this study was to verify whether computer-assisted total knee arthroplasty (CAS-TKA) lowers the incidence of PJI as compared with CONV-TKA. METHODS: A propensity score matching study of 5342 patients who underwent CAS-TKA (n = 1085) or CONV-TKA (n = 4257) for primary osteoarthritis of the knee from 2007 to 2015 in our institute was performed. Patients who underwent CAS-TKA were matched to those who received CONV-TKA at a 1:2 ratio according to demographics and comorbidities. PJI was defined according to the Musculoskeletal Infection Society diagnostic criteria from the 2013 International Consensus Meeting. RESULTS: After controlling potential risk factors, the use of CAS-TKA resulted in a lower incidence of PJI as compared with CONV-TKA [adjusted hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.18-0.99]. The same trend in PJI reduction was observed with the usage of CAS-TKA under sensitivity testing [HR, 0.33; 95% CI, 0.12-0.95]. The cumulative incidence of PJI was lower in the CAS-TKA group than the CONV-TKA group (log-rank test, p = 0.013). CONCLUSION: Avoidance of intramedullary violation during TKA may play a pivotal role in lowering the incidence of PJI. The use of CAS-TKA can reduce the incidence of PJI, with a better survival rate in terms of being free of PJI, as compared with CONV-TKA.

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.

The Application of Focused Medium-Energy Extracorporeal Shockwave Therapy in Hemophilic A Arthropathy.

Hemophilic arthropathy causes the damage of synovium, cartilage, and subchondral bone. The present study evaluated the safety and the effect of extracorporeal shockwave therapy (ESWT), a safe treatment widely used in musculoskeletal conditions in patients with hemophilic arthropathy. Between 1 August 2019 and 31 July 2020, seven hemophilia A patients were enrolled and treated with medium-energy ESWT on the knee joint in the first two months after prophylactic coagulation factor administration. At the beginning of the study and at 1-, 2-, 3-, and 6-month follow-ups, the Hemophilia Joint Health Score (HJHS), visual analog scale score (VAS), and Hemophilia Early Arthropathy Detection with Ultrasound score (HEAD-US) were evaluated for therapeutic effectiveness and safety, while serum bone morphogenetic protein 2 (BMP-2) and von Willebrand factor (vWF) levels were analyzed for assessing chondroprotection and bone healing. Magnetic resonance imaging (MRI) of the knee was performed at the beginning of the study and the 6-month follow-ups. As a result, a non-significant decrease in VAS scores (p = 0.151) but not HJHS after treatment was noticed. At the 3-month follow-up, there was a non-significant increase in BMP2 levels (p = 0.171) but not vWF. Ultrasonography showed no disease activity score elevation in five patients and no further disease damage in all patients. Repeated MRI examinations in three patients showed no structural progression during the 6-month follow-up. As to adverse events, redness, local heat, and mild swelling were noted in five patients without breakthrough bleeding. We concluded that medium-energy ESWT might be safe for hemophilic arthropathy once prophylactic coagulation factors are administered.

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.