Dichotomous Expression of TNF Superfamily Ligands on Antigen-Presenting Cells Controls Post-priming Anti-viral CD4+ T Cell Immunity.

T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4+ T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs). Mice with hypofunctional GITRL in Lyz2+ cells had decreased LCMV-specific CD4+ T cell accumulation and increased viral load. GITR signals in CD4+ T cells occurred after priming to upregulate OX40, CD25, and chemokine receptor CX3CR1. Thus IFN-I (signal 3) induced a post-priming checkpoint (signal 4) for CD4+ T cell accumulation, revealing a division of labor between cDCs and monocyte-derived APCs in regulating T cell expansion.

Enhanced Calvarial Bone Repair Using ASCs Engineered with RNA-Guided Split dCas12a System that Co-Activates Sox 5, Sox6, and Long Non-Coding RNA H19.

Healing of large calvarial bone defects remains challenging. An RNA-guided Split dCas12a system is previously harnessed to activate long non-coding RNA H19 (lncRNA H19, referred to as H19 thereafter) in bone marrow-derived mesenchymal stem cells (BMSCs). H19 activation in BMSCs induces chondrogenic differentiation, switches bone healing pathways, and improves calvarial bone repair. Since adipose-derived stem cells (ASCs) can be harvested more easily in large quantity, here it is aimed to use ASCs as an alternative cell source. However, H19 activation alone using the Split dCas12a system in ASCs failed to elicit evident chondrogenesis. Therefore, split dCas12a activators are designed more to co-activate other chondroinductive transcription factors (Sox5, Sox6, and Sox9) to synergistically potentiate differentiation. It is found that co-activation of H19/Sox5/Sox6 in ASCs elicited more potent chondrogenic differentiation than activation of Sox5/Sox6/Sox9 or H19 alone. Co-activating H19/Sox5/Sox6 in ASCs significantly augmented in vitro cartilage formation and in vivo calvarial bone healing. These data altogether implicated the potentials of the Split dCas12a system to trigger multiplexed gene activation in ASCs for differentiation pathway reprogramming and tissue regeneration.

Psychometric and structural properties of the traditional Chinese version of the sleep condition indicator for patients undergoing hemodialysis.

PURPOSE: Insomnia is a prevalent sleep disorder among patients undergoing hemodialysis for chronic kidney disease. This study aimed to translate the sleep condition indicator (SCI), an insomnia screening tool based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), into a traditional Chinese version (SCI-TC) and evaluate the reliability and validity of this version for patients undergoing hemodialysis. METHODS: This cross-sectional study conducted from November 2022 to June 2023 involved 200 patients on hemodialysis (mean age, 65.56 years; 61.5% men). Participants completed a series of questionnaires, with insomnia diagnosed according to DSM-5 criteria as the gold standard. A receiver operating characteristic (ROC) curve analysis was conducted to examine the sensitivity and specificity of the SCI-TC. RESULTS: According to the DSM-5 criteria, 38% of the participants had insomnia. Cronbach's alpha for the SCI-TC was 0.92. The SCI-TC exhibited a good fit as a two-factor model, and its scores were significantly associated with those of the traditional Chinese versions of the Insomnia Severity Index, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, EuroQol 5-Dimensions scale, and EuroQol Visual Analogue Scale (r = - 0.94, - 0.53, - 0.38, 0.27, and 0.30, respectively; all p < 0.05). The ROC curve analysis revealed an optimal cutoff of 16 points, with the sensitivity, specificity, and area under curve of 88.2%, 84.7%, and 0.91(95% confidence interval, 0.87-0.95), respectively. CONCLUSION: The SCI-TC demonstrates robust reliability and validity in detecting insomnia among patients undergoing hemodialysis. These findings suggest that health-care providers should considering using the SCI as an easy-to-use tool for the timely detection of insomnia in this population.

Survivorship of the fixed-bearing medial unicompartmental knee arthroplasty: mean 14-year follow-up in a single medical center.

BACKGROUND: This study aimed to report the long-term survival of fixed-bearing medial unicompartmental knee arthroplasty (UKA) with a mean of 14-year follow-up, and to determine possible risk factors of failure. METHODS: We retrospectively evaluated 337 fixed-bearing medial UKAs implanted between 2003 and 2014. Demographic and radiographic parameters were measured, including pre-operative and post-operative anatomical femorotibial angle (aFTA), posterior tibial slope (PTS), and anatomical medial proximal tibial angle (aMPTA). Multivariate logistic regression analysis was applied to figure out risk factors. RESULTS: The mean follow-up time was 14.0 years. There were 32 failures categorized into implant loosening (n = 11), osteoarthritis progression (n = 7), insert wear (n = 7), infection (n = 4), and periprosthetic fracture (n = 3). Cumulative survival was 91.6% at 10 years and 90.0% at 15 years. No statistically significant parameters were found between the overall survival and failure groups. Age and hypertension were significant factors of implant loosening with odds ratio (OR) 0.909 (p = 0.02) and 0.179 (p = 0.04) respectively. In the insert wear group, post-operative aFTA and correction of PTS showed significance with OR 0.363 (p = 0.02) and 0.415 (p = 0.03) respectively. Post-operative aMPTA was a significant factor of periprosthetic fracture with OR 0.680 (p < 0.05). CONCLUSIONS: The fixed-bearing medial UKA provides successful long-term survivorship. Tibial component loosening is the major cause of failure. Older age and hypertension were factors with decreased risk of implant loosening.

A Water-Based Biocoating to Increase the Infection Resistance and Osteoconductivity of Titanium Surfaces.

As the population ages, the number of patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) continues to increase. Infections after primary arthroplasty are rare but have high rates of morbidity and mortality, as well as enormous financial implications for healthcare systems. Numerous methods including the use of superhydrophobic coatings, the incorporation of antibacterial agents, and the application of topographical treatments have been developed to reduce bacterial attachment to medical devices. However, most of these methods require complex manufacturing processes. Thus, the main purpose of this study was to apply biocoatings to titanium (Ti) surfaces to increase their infection resistance and osteoconductivity via simple processes, without organic reagents. We modified titanium surfaces with a combination of aminomalononitrile (AMN) and an antibiotic-loaded mesoporous bioactive glass (MBG) and evaluated both the antibacterial effects of the coating layer and its effect on osteoblast proliferation and differentiation. The properties of the modified surface, such as the hydrophilicity, roughness, and surface morphology, were characterized via contact angle measurements, atomic force microscopy, and scanning electron microscopy. The cell proliferation reagent WST-1 assay and the alkaline phosphatase (ALP) assay were used to determine the degrees of adhesion and differentiation, respectively, of the MG-63 osteoblast-like cells on the surface. Antimicrobial activity was evaluated by examining the survival rate and inhibition zone of Escherichia coli (E. coli). The AMN coating layer reduced the water contact angle (WCA) of the titanium surface from 87° ± 2.5° to 53° ± 2.3° and this change was retained even after immersion in deionized water for five weeks, demonstrating the stability of the AMN coating. Compared with nontreated titanium and polydopamine (PDA) coating layers, the AMN surface coating increased MG-63 cell attachment, spreading, and early ALP expression; reduced E. coli adhesion; and increased the percentage of dead bacteria. In addition, the AMN coating served as an adhesion layer for the subsequent deposition of MBG-containing antibiotic nanoparticles. The synergistic effects of the AMN layer and antibiotics released from the MBG resulted in an obvious E. coli inhibition zone that was not observed in the nontreated titanium group.

Full analysis on coupling strengths between split ring resonators for double negative microwave tight-binding models.

Previous studies have shown that split-ring resonators (SRRs) can be utilized to achieve finely tuned nearest-neighbor coupling strengths in various one-dimensional hopping models. In our study, we present a systematic investigation of resonator coupling, providing a comprehensive quantitative description of the interaction between SRRs and complementary split-ring resonators (CSRRs) for any orientation combination. Our method includes an estimation of the coupling strength through a linear combination of periodic functions based on two orientation angles, with a sinusoidal expansion of up to the 3rd order, allowing for efficient and streamlined microwave structure design. Through our approach, we offer a satisfactory explanation of the band structure of SRR chains using a microwave-hopping model, which facilitates the exploration of exotic photonic band structures based on tight-binding theory.

Bi-directional gene activation and repression promote ASC differentiation and enhance bone healing in osteoporotic rats.

Calvarial bone healing is challenging, especially for individuals with osteoporosis because stem cells from osteoporotic patients are highly prone to adipogenic differentiation. Based on previous findings that chondrogenic induction of adipose-derived stem cells (ASCs) can augment calvarial bone healing, we hypothesized that activating chondroinductive Sox Trio genes (Sox5, Sox6, Sox9) and repressing adipoinductive genes (C/ebp-α, Ppar-γ) in osteoporotic ASCs can reprogram cell differentiation and improve calvarial bone healing after implantation. However, simultaneous gene activation and repression in ASCs is difficult. To tackle this problem, we built a CRISPR-BiD system for bi-directional gene regulation. Specifically, we built a CRISPR-AceTran system that exploited both histone acetylation and transcription activation for synergistic Sox Trio activation. We also developed a CRISPR interference (CRISPRi) system that exploited DNA methylation for repression of adipoinductive genes. We combined CRISPR-AceTran and CRISPRi to form the CRISPR-BiD system, which harnessed three mechanisms (transcription activation, histone acetylation, and DNA methylation). After delivery into osteoporotic rat ASCs, CRISPR-BiD significantly enhanced chondrogenesis and in vitro cartilage formation. Implantation of the engineered osteoporotic ASCs into critical-sized calvarial bone defects significantly improved bone healing in osteoporotic rats. These results implicated the potential of the CRISPR-BiD system for bi-directional regulation of cell fate and regenerative medicine.

Validation of the Generalized Anxiety Disorder-7 in patients with COPD: a cross-sectional study.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often have comorbid generalized anxiety disorder (GAD), which requires early screening in respiratory clinics. The Generalized Anxiety Disorder-7 (GAD-7) questionnaire is a brief and commonly used screening tool for GAD but has not been validated among patients with COPD in China. METHODS: Stable patients with COPD from a cross-sectional observational study were assessed using the GAD-7 questionnaire and then assessed by a senior psychiatrist to confirm a diagnosis of GAD according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Demographic characteristics, spirometry, and patient-reported outcomes were collected. Cronbach's α coefficient was calculated, and receiver operating curve (ROC) analysis was performed to validate the GAD-7. RESULTS: A total of 226 patients with COPD were enrolled, and 50 (22.1%) of these patients were diagnosed with GAD. The Cronbach's α coefficient for the GAD-7 was 0.869, which indicated good internal consistency. ROC curve analysis showed that the GAD-7 had an area under the curve (AUC) value of 0.829 (95% CI: 0.774-0.876) for identifying GAD. The optimal cut-off score was ≥ 4, with a sensitivity of 66.0% and a specificity of 89.2%. Higher GAD-7 scores were significantly associated with health-related quality of life and the symptom burden of COPD. The discriminatory power of GAD-7 did not differ statistically when stratified by COPD severity. CONCLUSIONS: The GAD-7 was shown to be a reliable and valid screening tool for patients with COPD in China, and its screening performance for GAD was not influenced by disease severity.

Clinical outcomes of various types of revision surgeries after unicompartmental knee arthroplasty failure.

PURPOSE: The advantages of unicompartmental knee arthroplasty (UKA) have led to the procedure being increasingly performed worldwide. However, revision surgery is required after UKA failure. According to the literature review, the choice of implant in revision surgery remains a debatable concern. This study analyzed the clinical results of different types of prostheses used in treating failed UKA. MATERIALS AND METHODS: This is a retrospective review of 33 failed medial UKAs between 2006 and 2017. Demographic data, failure reason, types of revision prostheses, and the severity of bone defects were analyzed. The patients were classified into three groups: primary prosthesis, primary prosthesis with a tibial stem, and revision prosthesis. The implant survival rate and medical cost of the procedures were compared. RESULTS: A total of 17 primary prostheses, 7 primary prostheses with tibial stems, and 9 revision prostheses were used. After a mean follow-up of 30.8 months, the survival outcomes of the three groups were 88.2%, 100%, and 88.9%, respectively (P = 0.640). The common bone defect in tibia site is Anderson Orthopedic Research Institute [AORI] grade 1 and 2a (16 versus 17). In patients with tibial bone defects AORI grade 2a, the failure rates of primary prostheses and primary prostheses with tibial stems were 25% and 0%, respectively. CONCLUSIONS: The most common cause for UKA failure was aseptic loosening. The adoption of a standardized surgical technique makes it easier to perform revision surgeries. Primary prostheses with tibial stems provided higher stability, leading to a lower failure rate due to less risk of aseptic loosening in patients with tibial AORI grade 2a. In our experience, we advise surgeons may try using primary prostheses in patients with tibial AORI grade 1 and primary prostheses with tibial stems in patients with tibial AORI grade 2a.

Risk Factors for Treatment Failure in Patients Who Have Knee Periprosthetic Joint Infection Treated With Two-Stage Exchange Arthroplasty as Well as Their Fate.

BACKGROUND: Two-stage exchange arthroplasty is considered the gold standard treatment for chronic periprosthetic joint infection (PJI). However, there is a scarcity of research investigating the major risk factors for infection recurrence and the prognosis after infection recurrence. METHODS: This study included 203 patients who underwent 2-stage exchange arthroplasty between June 22, 2010 and January 24, 2017. The need of reoperation for infection-related or PJI-related mortality was considered treatment failure. Participant age, gender, body mass index, comorbidities, culture results, length of hospital stay, cause of treatment failure, operative procedure, and fate were analyzed. RESULTS: Fifty-three patients experienced treatment failure (26.1%). Mean follow-up was 63 months (range, 26-103). Based on the multivariate analyses, risk factors for treatment failure included men and positive intraoperative culture during reimplantation. Recurrent infection was most commonly caused by Staphylococcus aureus (32.1%, 17/53), and new microorganisms caused recurrent infection in 34 of 53 (64.2%) patients. In 44 patients who had treatment failure, debridement, antibiotic therapy, irrigation, and retention of prosthesis (DAIR) performed within 6 months of reimplantation and at <3 weeks from symptom onset resulted in a significantly higher success rate than the use of other DAIR protocols (P = .031). CONCLUSION: Men and positive intraoperative culture are major risk factors for 2-stage exchange arthroplasty failure in patients who have knee PJI. Recurrent infection in these patients is usually caused by new microorganisms. DAIR within 6 months of reimplantation and at <3 weeks from symptom onset results in good outcomes in these patients.

Topical Fibrin Sealant (Tisseel@) Does Not Provide a Synergic Blood-Conservation Effect with Tranexamic Acid in Total Knee Arthroplasty-A Prospective Randomized Controlled Trial.

Background and Objectives: The efficacy of tranexamic acid (TXA) in reducing perioperative blood loss during total knee arthroplasty (TKA) is well established. However, the potential synergistic blood-conservation effect of topical fibrin sealant (Tisseel@) remains unclear. This study aims to assess the effectiveness of the combination of Tisseel and TXA during TKA. Materials and Methods: A single-blinded, prospective, randomized controlled trial was conducted with 100 patients (100 knees) undergoing primary TKA. Participants were randomly assigned to either the TXA group (n = 50), receiving intravenous (IV) TXA, or the Tisseel@ + TXA group (n = 50), receiving intra-articular Tisseel@ combined with IV TXA. The primary outcomes included blood transfusion rate, decrease in Hb level, calculated blood loss, and estimated total postoperative blood loss. Secondary outcomes involved assessing clinical differences between the groups. Results: The transfusion rate was zero in both groups. The average estimated blood loss in the Tisseel@ + TXA group was 0.463 ± 0.2422 L, which was similar to that of the TXA group at 0.455 ± 0.2522 L. The total calculated blood loss in the Tisseel@ + TXA group was 0.259 ± 0.1 L, compared with the TXA group's 0.268 ± 0.108 L. The mean hemoglobin reduction in the first 24 h postoperatively was 1.57 ± 0.83 g/dL for the Tisseel@ + TXA group and 1.46 ± 0.82 g/dL for the TXA-only group. The reduction in blood loss in the topical Tisseel@ + TXA group was not significantly different from that achieved in the TXA-only group. The clinical results of TKA up to the 6-week follow-up were comparable between the groups. Conclusions: The combination of the topical fibrin sealant Tisseel@ and perioperative IV TXA administration, following the described protocol, demonstrated no significant synergistic blood-conservation effect in patients undergoing TKR.

First Results from the Taiwan Axion Search Experiment with a Haloscope at 19.6 µeV.

This Letter reports on the first results from the Taiwan Axion Search Experiment with a Haloscope, a search for axions using a microwave cavity at frequencies between 4.707 50 and 4.798 15 GHz. Apart from the nonaxion signals, no candidates with a significance of more than 3.355 were found. The experiment excludes models with the axion-two-photon coupling |g_{aγγ}|≳8.1×10^{-14} GeV^{-1}, a factor of eleven above the benchmark Kim-Shifman-Vainshtein-Zakharov model, in the mass range 19.4687

Application of structural allogenous bone graft in two-stage exchange arthroplasty for knee periprosthetic joint infection: a case control study.

BACKGROUND: Knee prosthetic joint infection (PJI) is a common but devastating complication after knee arthroplasty. The revision surgeries for knee PJI may become more challenging when it is associated with large bone defects. The application of structural bone allograft in knee revision surgeries with large bone defects is not a new technique. However, there is a lack of literature reporting its efficacy in PJI cases. This study aimed to investigate the outcome of structural fresh frozen allogenous bone grafts in treating patients in knee PJI with large bone defects. METHODS: We performed a retrospective cohort analysis of knee PJI cases treated with two-stage exchange arthroplasty at our institution from 2010 to 2016. 12 patients with structural allogenous bone graft reconstructions were identified as the study group. 24 patients without structural allograft reconstructions matched with the study group by age, gender, and Charlson comorbidity index were enrolled as the control group. The functional outcome of the study group was evaluated with the Knee Society Score (KSS). Treatment success was assessed according to the Delphi-based consensus definition. The infection relapse rate and implant survivorship were compared between groups. RESULTS: Revision knees with structural allograft presented excellent improvement in the KSS (33.1 to 75.4). There was no significant difference between infection relapse-free survival rate and prosthesis survival rate in the two groups. The 8-year prosthesis survival rate was 90.9% in the study group and 91% in the control group (p = 0.913). The 8-year infection relapse-free survival rate was 80 and 83.3% in the study group and control group, respectively (p = 0.377). CONCLUSION: The structural fresh frozen allogenous bone graft provided an effective way for bone defect reconstruction in knee PJI with an accountable survival rate. Meanwhile, using structural allografts did not increase the relapse rate of infection.

Coactivation of Endogenous Wnt10b and Foxc2 by CRISPR Activation Enhances BMSC Osteogenesis and Promotes Calvarial Bone Regeneration.

CRISPR activation (CRISPRa) is a burgeoning technology for programmable gene activation, but its potential for tissue regeneration has yet to be fully explored. Bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into osteogenic or adipogenic pathways, which are governed by the Wnt (Wingless-related integration site) signaling cascade. To promote BMSC differentiation toward osteogenesis and improve calvarial bone healing by BMSCs, we harnessed a highly efficient hybrid baculovirus vector for gene delivery and exploited a synergistic activation mediator (SAM)-based CRISPRa system to activate Wnt10b (that triggers the canonical Wnt pathway) and forkhead c2 (Foxc2) (that elicits the noncanonical Wnt pathway) in BMSCs. We constructed a Bac-CRISPRa vector to deliver the SAM-based CRISPRa system into rat BMSCs. We showed that Bac-CRISPRa enabled CRISPRa delivery and potently activated endogenous Wnt10b and Foxc2 expression in BMSCs for >14 days. Activation of Wnt10b or Foxc2 alone was sufficient to promote osteogenesis and repress adipogenesis in vitro. Furthermore, the robust and prolonged coactivation of both Wnt10b and Foxc2 additively enhanced osteogenic differentiation while inhibiting adipogenic differentiation of BMSCs. The CRISPRa-engineered BMSCs with activated Wnt10b and Foxc2 remarkably improved the calvarial bone healing after implantation into the critical-sized calvarial defects in rats. These data implicate the potentials of CRISPRa technology for bone tissue regeneration.

Effect of hydrophilic and lipophilic statins on early onset cataract: A nationwide case-control study.

BACKGROUND: Statin is biologically plausible in cataract development, but inconclusive associations between statin and cataract are presented in human studies. Given most early onset cataract (EOC) occurs in regions with high cholesterol composition, we therefore aimed to assess the association between statin and EOC. METHODS: A population based case-control study was performed using the Taiwan National Health Insurance Research Database (NHIRD). The case involved patients aged 20-55 years with EOC. Controls were 1:1 matched by age, gender, year of index date, and propensity score estimated from comorbidities and comedications. Statin exposure, including intensity, properties and cumulative exposure one year before the index date were tracked. The odds ratios (ORs) of EOC associated with statin were estimated by conditional logistic regression. RESULTS: A total of 4213 cases and 4213 controls were included. Statins were associated with EOC (OR = 3.257, 95% CI 2.519-4.211). The ORs of cataract was positively associated with cumulative exposure. Subgroup analysis indicated that the ORs of cataract were significant both in lipophilic (OR = 3.485, 95% CI 2.606-4.659) and hydrophilic (OR = 3.241, 95% CI 1.975-5.321) statin users. CONCLUSIONS: Statins were associated with an increased risk of cataract in young populations.

Two-stage exchange Arthroplasty for knee Periprosthetic joint infection exhibit high infection recurrence rate in patients with chronic viral hepatitis.

BACKGROUND: Currently, there is little evidence about the outcome of two-stage exchange arthroplasty for the treatment of knee periprosthetic joint infection (PJI) in patients with chronic viral hepatitis. To evaluate it, we set the primary outcome as infection recurrence, and the secondary outcome as the difference between patients diagnosed with hepatitis B virus or hepatitis C virus. PATIENTS AND METHODS: Between June, 2010 and December, 2016, 172 patients with knee PJIs were treated with two-stage exchange arthroplasty at our institute. Treatment success was defined using Delphi-based consensus. These patients were further divided into groups with or without chronic hepatitis. Variables were analyzed, including age, sex, comorbidities, microbiology, and operative methods. Minimum follow-up was 12 months (mean, 35 months; range, 12-85 months). RESULTS: Of the 172 knee PJI patients, 25 were identified with chronic hepatitis. The infection recurrence rate in the hepatitis group (28%, 7 in 25) was significantly higher than that in the non-hepatitis group (9.5%, 14 in 147), p = 0.017. However, there was no significant difference in the infection recurrence rates between patients with HBV (24%, 4 in 16) and HCV (33.3%, 3 in 9). Regarding the outcomes of patients with infection recurrence, 4 of the non-hepatitis patients were treated with the debridement, antibiotic treatment, irrigation, and retention of prosthesis (DAIR) procedure, with a success rate of 75%. The other 17 patients (7 with hepatitis and 10 without) were treated with repeated two-stage exchange arthroplasty with 100% infection elimination rate until the final follow-up. CONCLUSIONS: Knee PJI patients with chronic hepatitis have higher infection recurrence rate after two-stage exchange arthroplasty (28%).

The Risk Factor and Outcome of Metachronous Periprosthetic Joint Infections: A Retrospective Analysis With a Minimum Ten-Year Follow-Up.

BACKGROUND: Patients with multiple prosthetic joints are at risk of developing periprosthetic joint infections (PJIs). We aimed to determine whether PJI development at one site may lead to infection at another prosthetic joint site and assess the risk factors leading to this subsequent infection. METHODS: We reviewed all cases (294 patients with first-time PJI [159 hips, 135 knees]) with PJI treated at our institute between January 1994 and December 2020. The average follow-up period was 11.2 years (range 10.1-23.2). Patients were included if they had at least one other prosthetic joint at the time of developing a single PJI (96 patients). Patients with synchronous PJI were excluded from the study. The incidence of metachronous PJI was assessed, and the risk factors were determined by comparing different characteristics between patients without metachronous PJI. RESULTS: Of the 96 patients, 19.79% developed metachronous PJI. The identified causative pathogen was the same in 63.16% of the patients. The time to developing a second PJI was 789.84 days (range 10-3386). The identified risk factors were PJI with systemic inflammatory response syndrome, ≥3 stages of resection arthroplasty, and PJI caused by methicillin-resistant Staphylococcus aureus. CONCLUSION: PJI may predispose patients to subsequent PJI in another prosthesis with identified risks. Most causative organisms of metachronous PJI were the same species as those of the first PJI. We believe that bacteremia may be involved in pathogenesis, but further research is required.

Ibudilast Mitigates Delayed Bone Healing Caused by Lipopolysaccharide by Altering Osteoblast and Osteoclast Activity.

Bacterial infection in orthopedic surgery is challenging because cell wall components released after bactericidal treatment can alter osteoblast and osteoclast activity and impair fracture stability. However, the precise effects and mechanisms whereby cell wall components impair bone healing are unclear. In this study, we characterized the effects of lipopolysaccharide (LPS) on bone healing and osteoclast and osteoblast activity in vitro and in vivo and evaluated the effects of ibudilast, an antagonist of toll-like receptor 4 (TLR4), on LPS-induced changes. In particular, micro-computed tomography was used to reconstruct femoral morphology and analyze callus bone content in a femoral defect mouse model. In the sham-treated group, significant bone bridge and cancellous bone formation were observed after surgery, however, LPS treatment delayed bone bridge and cancellous bone formation. LPS inhibited osteogenic factor-induced MC3T3-E1 cell differentiation, alkaline phosphatase (ALP) levels, calcium deposition, and osteopontin secretion and increased the activity of osteoclast-associated molecules, including cathepsin K and tartrate-resistant acid phosphatase in vitro. Finally, ibudilast blocked the LPS-induced inhibition of osteoblast activation and activation of osteoclast in vitro and attenuated LPS-induced delayed callus bone formation in vivo. Our results provide a basis for the development of a novel strategy for the treatment of bone infection.

Uptake and Depuration Kinetics of Pacific Ciguatoxins in Orange-Spotted Grouper (Epinephelus coioides).

Ciguatoxins (CTXs), produced by toxic benthic dinoflagellates, can bioaccumulate in marine organisms at higher trophic levels. The current study evaluated the uptake and depuration kinetics of some of the most potent CTXs, Pacific CTX-1, -2, and -3 (P-CTX-1, -2, and -3), in orange-spotted grouper (Epinephelus coioides) exposed to 1 ng P-CTXs g-1 fish daily. Over a 30 d exposure, P-CTX-1, -2, and -3 were consistently detected in various tissues of exposed fish, and the concentrations of the total P-CTXs in tissues generally ranked following the order of liver, intestine, gill, skin, brain, and muscle. Relatively higher uptake rates of P-CTX-1 in the groupers were observed compared with those of P-CTX-2 and -3. The depuration rate constants of P-CTX-1, -2, and -3 in different tissues were (0.996-16.5) × 10-2, (1.51-16.1) × 10-2, and (0.557-10.6) × 10-2 d-1, respectively. The accumulation efficiencies of P-CTX-1, -2, and -3 in whole groupers were 6.13%, 2.61%, and 1.15%, respectively. The increasing proportion of P-CTX-1 and the decreasing proportion of P-CTX-2 and -3 over the exposure phase suggest a likely biotransformation of P-CTX-2 and -3 to P-CTX-1, leading to higher levels of P-CTX-1 in fish and possibly a higher risk of CTXs in long-term exposed fish.

Influence of extension stem length and diameter on clinical and radiographic outcomes of revision total knee arthroplasty.

BACKGROUND: Extension stems provide stability to revision total knee arthroplasty (RTKA). Little is known regarding the relationship between stem characteristics and RTKA stability. We aimed to identify the relationship between canal filling ratio (CFR) and aseptic loosening following RTKA. METHODS: We retrospectively reviewed demographics, radiographic parameters, and outcomes associated with RTKA performed between 2008 and 2013 in a tertiary hospital. The inclusion criteria were: revision for aseptic loosening, hybrid fixation, minor bone defect, Zimmer® LCCK prosthesis, and follow-up > 24 months. Using the modified Knee Society radiographic scoring system, radiographic prosthesis loosening was defined as a radiolucent line (RLL) score ≥ 9 on the femoral side or ≥ 10 on the tibial side. We utilized receiver operating characteristic (ROC) curve analysis to evaluate the cutoff value for stem length and diameter in terms of prosthesis loosening or not. Furthermore, CFR-related parameters were analyzed with logistic regression to clarify their relationships with prosthesis loosening. RESULTS: Prosthesis loosening was detected in 17 of 65 patients included. On logistic regression analysis, male sex and severity of the tibial bone defect were associated with loosening. On multivariate analysis, male sex and bone defect severity were associated with loosening on the femoral side, while malalignment was associated with loosening on the tibial side. Protective factors included femoral CFR > 0.85, CFR > 0.7 for > 2 cm, and CFR > 0.7 for > 4 cm, as well as tibial CFR > 0.85. CONCLUSIONS: To minimize loosening post-RTKA, femoral CFR > 0.7 for > 2 cm and tibial CFR > 0.85 are recommended. Risk factors may include male sex, bone defect severity, and malalignment.