Poly 2-methacryloyloxyethyl Phosphorylcholine Protects Corneal Cells and Contact Lenses from Desiccation Damage.

SIGNIFICANCE: Contact lens (CL) wearing may cause discomfort and eye dryness. We describe here the efficacy of a synthetic polymer in protecting both the corneal epithelial cells and the CL from desiccation damage. Artificial tears containing this polymer might be helpful to treat or prevent ocular surface damage in CL wearers. PURPOSE: We aimed to investigate the protective effects of the synthetic polymer 2-methacryloyloxyethyl phosphorylcholine (poly-MPC) on corneal epithelial cells and CLs subjected to desiccation damage. METHODS: The interaction of poly-MPC with the cell membrane was evaluated on human primary corneal epithelial cells (HCE-F) by the sodium dodecyl sulfate damage protection assay or the displacement of the cell-binding lectin concanavalin A (ConA). Survival in vitro of HCE-F cells and ex vivo of porcine corneas exposed to desiccating conditions after pre-treatment with poly-MPC or hyaluronic acid (HA), hypromellose (HPMC), and trehalose was evaluated by a colorimetric assay. Soft CLs were soaked overnight in a solution of poly-MPC/HPMC and then let dry in ambient air. Contact lens weight, morphology, and transparency were periodically registered until complete dryness. RESULTS: Polymer 2-methacryloyloxyethyl phosphorylcholine and HPMC were retained on the HCE-F cell membrane more than trehalose or HA. Polymer 2-methacryloyloxyethyl phosphorylcholine, HA, and HPMC either alone or in association protected corneal cells from desiccation significantly better than did trehalose alone or in association with HA. Contact lens permeation by poly-MPC/HPMC preserved better their shape and transparency than did saline. CONCLUSIONS: Polymer 2-methacryloyloxyethyl phosphorylcholine coats and protects corneal epithelial cells and CLs from desiccation damage more efficiently compared with trehalose and as good as other reference compounds.

Changes in Symptoms of Midday Fogging with a Novel Scleral Contact Lens Filling Solution.

SIGNIFICANCE: Midday fogging of scleral contact lenses requires frequent lens removal and reapplication for a large portion of lens wearers. Using a lens filling solution that mimics the composition of tears is hypothesized to have an impact on the production of material trapped under a scleral lens. PURPOSE: The purposes of this open-label study were to assess the safety of a scleral lens filling solution, which closely approximates the ionic concentration and pH of human tears, and to assess signs and symptoms of midday fogging with this formulation and with subjects' habitual sodium chloride solutions. METHODS: Existing scleral lens wearers with midday fogging (N = 22) were examined and completed surveys of symptoms. Subjects filled the concavity of their current lenses with test solution and were assessed immediately and approximately 4 hours later for safety monitoring. Test solution was dispensed and used for 5 to 9 days when subjects were reexamined and repeated the surveys. Biomicroscopy and anterior optical coherence tomography images were used to assess midday fogging objectively. RESULTS: The median (interquartile range) Ocular Surface Disease Index score decreased from 27.1 (21.7) U when using habitual filling solution to 9.1 (20.1) U when using the test solution (P = .006). Current Symptoms Survey findings with the test solution compared with habitual solution resulted in statistically significant decreases in burning/stinging (P = .04), grittiness/foreign body sensation (P = .01), dryness (P = .002), blurry/fluctuating vision (P = .002), and overall pain/discomfort (P = .006). Objective assessment of corneal staining and fogging revealed decreases that were not statistically significant in this small sample size. CONCLUSIONS: This study establishes the safety and subject tolerance of a scleral lens filling solution that mimics the ionic composition of human tears. Significant improvements in subjective ratings, although likely biased in this unmasked trial, suggest that further studies of the effectiveness of this solution in reducing midday fogging are warranted.

Misoprostol administration prior to intrauterine contraceptive device insertion: a systematic review and meta-analysis of randomised controlled trials.

Objectives: Misoprostol has been used before intrauterine contraceptive device (IUCD) insertion to prime the cervical os. As the literature about this topic is controversial, we aimed to evaluate IUCD insertion failure, women's pain perception, use of cervical dilators and prevalence of side effects following the administration of misoprostol.Methods: Trials published in MEDLINE, Scopus, the Cochrane Library and ClinicalTrials.gov were searched (last search on 23 October 2019). The primary outcome was IUCD insertion failure; secondary outcomes were women's pain perception, use of cervical dilators to facilitate insertion, and prevalence of side effects.Results: Fourteen studies were eligible for inclusion. Misoprostol premedication reduced IUCD insertion failure rates and the use of cervical dilators but significantly increased the prevalence of side effects. The risk of IUCD insertion failure with misoprostol premedication was reduced among women who had undergone previous caesarean section and among women who had experienced previous IUCD insertion failure. Nulliparas did not benefit from misoprostol premedication. Buccal misoprostol administration did not seem to be effective in reducing IUCD insertion failure. Visual analogue scale pain scores were increased with both sublingual and buccal misoprostol administration if IUCD insertion was performed ≤2.5 h after misoprostol premedication.Conclusion: Our data demonstrate reduced IUCD insertion failure among women with previous caesarean section and those with previous IUCD insertion failure, suggesting that misoprostol may be a reasonable choice in these groups of women. Although misoprostol premedication reduced insertion failures, it significantly increased side effects and had a heterogeneous pattern of efficacy; thus, its routine use is not supported by the evidence.

Cepharanthine ameliorates titanium particle-induced osteolysis by inhibiting osteoclastogenesis and modulating OPG/RANKL ratio in a murine model.

Periprosthetic asepteic loosening, caused by wear debris, is one of the most severe complications, generally resulting in implant failure. Extensive osteoclast formation and activation are considered as the cause for periprosthetic osteolysis. However, few approaches have been approved to be used for preventing early-stage periprosthetic osteolysis. In this study, we investigated the preventive effects of CEP on titanium particles-induced osteolysis in a murine calvaria model. This inhibitory effect was confirmed to be realized by attenuating osteoclastogenesis in vivo. In addition, CEP markedly reduced wear particles-induced elevation of receptor activator of nuclear factor kappa B ligand (RANKL)/Osteoprotegerin (OPG) ratio in vivo. In conclusion, these data concluded that CEP demonstrated a preventive effect of CEP on titanium particles induced osteolysis, suggesting that CEP might be a novel therapeutic for periprosthesis loosening.

Use of beta-blockers and risk of aseptic loosening in total hip and knee arthroplasty: a nested case - control study.

OBJECTIVES: To analyze the effect of beta-blockers on the risk of aseptic loosening (AL) in Total Hip (THA) or Knee (TKA) Arthroplasty. METHODS: A nested case-control study was conducted. Cases were patients who underwent revision surgery for THA or TKA due to AL. Controls were patients who sustained primary THA or TKA and were matched to cases in respect to age, sex, type of prostheses and follow-up in a 4:1 ratio. The use of beta-blockers was achieved. A logistic regression analysis adjusted to potential confounders was performed to determine the risk of AL. Analysis was also adjusted to cardioselectivity of the beta-blocker and the adherence to treatment, measured as Proportion of Days Covered (PDC). RESULTS: 24 cases and 96 controls were selected. Compared to non-users, any use of beta-blockers was associated with a reduced risk of AL [adjusted OR 0.141 (Confidence Interval (CI) 95% 0.04-0.86)]. Use of selective beta-blockers showed significant lower risk of AL [adjusted OR 0.112 (CI95% 0.01-0.91)]. PDC ≥50% was associated with reduced risk of AL compared to non-users [adjusted OR 0.083 (CI95% 0.01-0.66)]. CONCLUSION: The first clinical evidence showing an association between the use of beta-blockers and lower risk of aseptic loosening in THA and TKA is provided.

Protection Effect of Curcumin for Macrophage-Involved Polyethylene Wear Particle-Induced Inflammatory Osteolysis by Increasing the Cholesterol Efflux.

BACKGROUND Periprosthetic osteolysis, induced by wear particles and inflammation, is a common reason for failure of primary arthroplasty. Curcumin, a nature phenol from plants, has been reported to reduce the inflammation in macrophages. This study aimed to investigate the potential effect of curcumin on macrophage involved, wear particle-induced osteolysis and its mechanism. MATERIAL AND METHODS RAW264.7 macrophages were used to test the effects of polyethylene (PE) particles and curcumin on macrophage cholesterol efflux and phenotypic changes. A mouse model of PE particle-induced calvarial osteolysis was established to test the effects of curcumin in vivo. After 14 days of treatment, the bone quality of the affected areas was analyzed by micro-computed tomography (micro-CT) and histology, and the bone surrounding soft tissues were analyzed at the cellular and molecular levels. RESULTS We found that PE particles can stimulate osteoclastogenesis and produce an M1-like phenotype in macrophages in vitro. Curcumin enhanced the cholesterol efflux in macrophages, and maintained the M0-like phenotype under the influence of PE particles in vitro. Additionally, the cholesterol transmembrane regulators ABCA1, ABCG1, and CAV1 were enhanced by curcumin in vivo. We also found enhanced bone density, reduced osteoclastogenesis, and fewer inflammatory responses in the curcumin treated groups in our mouse osteolysis model. CONCLUSIONS Our study findings indicated that curcumin can inhibit macrophage involved osteolysis and inflammation via promoting cholesterol efflux. Maintaining the cholesterol efflux might be a potential strategy to prevent periprosthetic osteolysis after total joint arthroplasty surgery.

The use of bisphosphonates after joint arthroplasty is associated with lower implant revision rate.

PURPOSE: This study hypothesized that the use of bisphosphonates (BPs) after total joint arthroplasty (TJA) is associated with a lower implant revision rate. This study aimed (1) to investigate the association between BP use and the revision rate of TJA and (2) to determine the relationship between the medication period and the revision rate of TJA. METHODS: National Health Insurance Service data on surgeries, medications, diagnoses, and screenings of 50 million Koreans were reviewed. People who underwent TJA in the period from 2002 to 2012 were identified and followed until 2016. During that period, 331,660 patients underwent total knee arthroplasty (TKA), and 56,043 patients underwent total hip arthroplasty (THA). Among them, 8447 knee patients (2.5%) and 2851 hip patients (5.0%) required revision surgery due to aseptic loosening. Demographic data, the duration of BP medication, and comorbidities were identified. The rate of revision surgery according to BP medication was investigated. The extended Cox proportional hazard model was used to evaluate the effect of the medication period. RESULTS: The rate of TKA revision was 1.4% for BP users and 2.9% for BP non-users (p < 0.001). The THA revision rate was 2.8% and 5.3% for BP users and non-users, respectively (p < 0.001). The hazard ratio (HR) of revision was significantly lower in patients who took BP medication for more than one year (TKA HR = 0.472, 95% CI [0.350-0.637]; THA HR = 0.490, 95% CI [0.247-0.972]) compared to that in short-term users (less than 1 year). CONCLUSIONS: The use of BPs after TJA was associated with a lower revision rate. The use of BPs for more than one year further reduced the risk of revision. Bisphosphonate use can be highly recommended to reduce the revision rate of TJA. LEVEL OF EVIDENCE: Retrospective cohort study, Level III.

Effects of vitamin E incorporation in polyethylene on oxidative degradation, wear rates, immune response, and infections in total joint arthroplasty: a review of the current literature.

Highly cross-linked ultrahigh molecular weight polyethylene (UHMWPE) was introduced to decrease wear debris and osteolysis. During cross-linking, free radicals are formed, making highly cross-linked polyethylene vulnerable to oxidative degradation. In order to reduce this process, anti-oxidant vitamin E can be incorporated in polyethylene. This review provides an overview of the effects of vitamin E incorporation on major complications in total joint arthroplasty: material failure due to oxidative degradation, wear debris and subsequent periprosthetic osteolysis, and prosthetic joint infections. Secondly, this review summarizes the first clinical results of total hip and knee arthroplasties with vitamin E incorporated highly cross-linked polyethylene. Based on in vitro studies, incorporation of vitamin E in polyethylene provides good oxidative protection and preserves low wear rates. Incorporation of vitamin E may have the beneficial effect of reduced inflammatory response to its wear particles. Some microorganisms showed reduced adherence to vitamin E-incorporated UHMWPE; however, clinical relevance is doubtful. Short-term clinical studies of total hip and knee arthroplasties with vitamin E-incorporated highly cross-linked UHMWPE reported good clinical results and wear rates similar to highly cross-linked UHMWPE without vitamin E.

Bisphosphonates for the preservation of periprosthetic bone mineral density after total joint arthroplasty: a meta-analysis of 25 randomized controlled trials.

The present meta-analysis aimed to evaluate the long-term efficacy of bisphosphonates (BPs) on preservation of periprosthetic bone mineral density (BMD) after joint arthroplasty. It confirmed the protective effect of BPs in a long-term follow-up, and found the influence factors on this effect. INTRODUCTION: Periprosthetic bone loss is believed to cause aseptic loosening and failed prosthetic fixation in joint arthroplasty. This meta-analysis which included high-quality randomized controlled trials aimed to analyze the effect of bisphosphonates on maintaining periprosthetic bone mineral density after total joint arthroplasty. METHODS: Twenty-five RCTs were included and the total number of participants was 1163 by computerized searches of bibliographic databases. The weighted mean differences with 95% confidence interval were calculated to evaluate the efficacy of BPs on total periprosthetic BMD and the BMD of different Gruen zones. Subgroup analyses identified the potentially influencing factors such as surgical site, cement fixation, and generation of BPs. A descriptive review was conducted for BP-related adverse effects. RESULTS: The BPs group presented significantly higher total periprosthetic BMD in the BPs group than that in the control group at 3, 6, 12 months, 2-4 years, and 5-10 years after arthroplasty (P < 0.05). The BPs group presented significantly higher periprosthetic BMD in femoral Gruen Zone 1 and 7 than that in the control group at 3, 6, 12 months, 2-4 years, and 5-10 years (P < 0.05). The heterogeneity was minimized by dividing THA and TKA into two subgroups. Subgroup analyses revealed that the effect of BPs on preservation of BMD was significantly greater in arthroplasty with cemented component than in that with uncemented component at 12 months and 5-10 years (P < 0.05), and the administration of the second and third generation BPs was significantly more effective than the first-generation BPs at 6 and 12 months (P < 0.05). None of the included studies described severe or fatal adverse effects related to BPs. CONCLUSIONS: BPs have significantly long-term efficacy on the preservation of periprosthetic BMD after joint arthroplasty. To obtain a better efficacy, the cemented components and the second and third generation BPs are recommended.

Modification of Cysteine 179 in IKKß by Ursolic Acid Inhibits Titanium-Wear-Particle-Induced Inflammation, Osteoclastogenesis, and Hydroxylapatite Resorption.

Aseptic loosening of artificial joints mainly accounts for the failure of arthroplasty. We previously reported that ursolic acid (UA) inhibited osteolysis caused by titanium (Ti) wear particles via suppression of NF-kB signaling. In the present study, that the suppressive effect of UA on Ti-particle-induced inflammation and osteoclastogenesis targets on IKKß cys-179 was demonstrated. A retrovirus packaged IKKßC179A plasmid with a Cys-179 mutation replaced by Ala was constructed. qRT-PCR, immunoblot, and immunofluorescence were used to evaluate the gene expressions. Secreted inflammatory cytokines were detected by ELISA. Formation and function of osteoclastogenesis were evaluated by TRAP stain and hydroxylapatite resorption assays. As a result, a mutation of IKKßC179A rescued the therapeutic effect of UA on Ti-particle-induced inflammation, including morphological transforms, upregulation of iNOS and COX-2, increased secretions of TNF-α, IL-1ß, and IL-6, and decreased secretion of IL-10. Meanwhile, inhibition of osteoclastogenesis and hydroxylapatite resorptions were restored by transfection of IKKßC179A. Phosphorylations of p65 and the IKKα/ß complex and translocation of p65 into the nucleus were suppressed by UA but rescued by a mutation of IKKßC179A. Conclusively, UA inhibits Ti-wear-particle-induced inflammation, osteoclastogenesis, and hydroxylapatite resorption via modifying cysteine 179 of IKKß.

Decreased migration with locally administered bisphosphonate in cemented cup revisions using impaction bone grafting technique.

Background and purpose - Impaction bone grafting (IBG) in revision hip surgery is an established method in restoring bone stock deficiencies. We hypothesized that local treatment of the morsellized allograft with a bisphosphonate in cemented revision would, in addition to increased bone density, also reduce the early migration of the cup as measured by radiostereometry (RSA). Patients and methods - 20 patients with aseptic cup loosening underwent revision using the IBG technique. The patients were randomized to either clodronate (10 patients) or saline (10 patients, control group) as local adjunct to the morsellized bone. The outcome was evaluated by dual-energy X-ray absorptiometry (DXA) during the first year regarding periacetabular bone density and with radiostereometric analysis (RSA) for the first 2 years regarding cup migration. Results - 2 patients were lost to follow-up: 9 patients remained in the clodronate and 9 in the control group. Less proximal migration was found in the clodronate group compared with the controls, measured both over time (mixed-models analysis, p = 0.02) as well as at the specified time points up to 2 years (0.22 mm and 0.59 mm respectively, p = 0.02). Both groups seemed to have stabilized at 1 year. We found similar bone mineral density measured by DXA, and similar RSA migration in the other directions. No cups were re-revised. Interpretation - Local treatment of the allograft bone with clodronate reduced early proximal migration of the revised cup but without any measurable difference in periacetabular bone density.

Using DR52c/Ni2+ mimotope tetramers to detect Ni2+ reactive CD4+ T cells in patients with joint replacement failure.

T cell mediated hypersensitivity to nickel (Ni2+) is one of the most common causes of allergic contact dermatitis. Ni2+ sensitization may also contribute to the failure of Ni2+ containing joint implants, and revision to non-Ni2+ containing hardware can be costly and debilitating. Previously, we identified Ni2+ mimotope peptides, which are reactive to a CD4+ T cell clone, ANi2.3 (Vα1, Vß17), isolated from a Ni2+ hypersensitive patient with contact dermatitis. This T cell is restricted to the major histocompatibility complex class II (MHCII) molecule, Human Leukocyte Antigen (HLA)-DR52c (DRA, DRB3*0301). However, it is not known if Ni2+ induced T cell responses in sensitized joint replacement failure patients are similar to subjects with Ni2+ induced contact dermatitis. Here, we generated DR52c/Ni2+ mimotope tetramers, and used them to test if the same Ni2+ T cell activation mechanism could be generalized to Ni2+ sensitized patients with associated joint implant failure. We confirmed the specificity of these tetramers by staining of ANi2.3T cell transfectomas. The DR52c/Ni2+ mimotope tetramer detected Ni2+ reactive CD4+ T cells in the peripheral blood mononuclear cells (PBMC) of patients identified as Ni2+ sensitized by patch testing and a positive Ni2+ LPT. When HLA-typed by a DR52 specific antibody, three out of four patients were DR52 positive. In one patient, Ni2+ stimulation induced the expansion of Vß17 positive CD4+ T cells from 0.8% to 13.3%. We found that the percentage of DR52 positivity and Vß17 usage in Ni2+ sensitized joint failure patients are similar to Ni sensitized skin allergy patients. Ni2+ independent mimotope tetramers may be a useful tool to identify the Ni2+ reactive CD4+ T cells.

Topical zoledronic acid decreases micromotion induced bone resorption in a sheep arthroplasty model.

BACKGROUND: Initial micromotion of a total hip replacement is associated with aseptic loosening. The use of bisphosphonates could be one way to reduce peri-implant bone resorption induced by micromotion. Bisphosphonates compounds are inhibitors of bone resorption. The aim of this study was to investigate whether local treatment with bisphosphonate would reduce bone resorption and fibrous tissue around an experimental implant subjected to micromotion. METHODS: One micromotion implant were inserted into each medial femoral condyle in ten sheep. During each gait cycle the implant axially piston 0.5 mm. During surgery one of the femoral condyles were locally treated with 0.8 mg zoledronate. The other condyle served as control. Observation period was 12 weeks. RESULTS: Histological evaluation showed a fibrous capsule around both the control and bisphosphonate implants. Histomorphometrical analysis showed that 97% of the surface on both control and bisphosphonate implants were covered by fibrous tissue. However, the bisphosphonate was able to preserve bone in a 1 mm zone around the implants. CONCLUSION: This study indicates that local treatment with bisphosphonate cannot prevent the formation of a fibrous capsule around an implant subjected to micromotion, but bisphosphonate is able to reduce resorption of peri-prosthetic bone.

Denosumab reduces early migration in total knee replacement.

Background and purpose - Aseptic loosening is a main cause of late revision in total knee replacement (TKR). Migration of implants as measured by radiostereometric analysis (RSA) can predict future loosening. This migration is associated with bone resorption. Denosumab is a human monoclonal antibody that binds to receptors on osteoclast precursors and osteoclasts. This prevents osteoclast formation, resulting in less bone resorption in cortical and trabecular bone. We investigated whether denosumab can reduce migration of TKR, as measured with RSA. Patients and methods - In this 2-center, randomized, double-blind placebo-controlled trial, 50 patients with osteoarthritis of the knee were treated with an injection of either denosumab (60 mg) or placebo 1 day after knee replacement surgery and again after 6 months. RSA was performed postoperatively and after 6, 12, and 24 months. The primary effect variable was RSA maximal total point motion (MTPM) after 12 months. We also measured other RSA variables and the knee osteoarthritis outcome score (KOOS). Results - The primary effect variable, MTPM after 12 months, showed that migration in the denosumab group was statistically significantly less than in the controls. Denosumab MTPM 12 months was reduced by one-third (denosumab: median 0.24 mm, 10% and 90% percentiles: 0.15 and 0.41; placebo: median 0.36 mm, 10% and 90% percentiles: 0.20 and 0.62). The secondary MTPM variables (6 and 24 months) also showed a statistically significant reduction in migration. There was no significant difference in MTPM for the period 12-24 months. KOOS sub-variables were similiar between denosumab and placebo after 12 and 24 months. Interpretation - Denosumab reduces early migration in total knee replacement, as in previous trials using bisphosphonates. As migration is related to the risk of late loosening, denosumab may be beneficial for long-term results.

No effect of teriparatide on migration in total knee replacement.

Background and purpose - Aseptic loosening is a main cause of late revision in total knee replacement (TKR). Teriparatide, a recombinant parathyroid hormone (PTH), stimulates osteoblasts and has been suggested to improve cancellous bone healing in humans. This might also be relevant for prosthesis fixation. We used radiostereometric analysis (RSA) to investigate whether teriparatide influences prosthesis fixation. Early migration as measured by RSA can predict future loosening. Patients and methods - In a randomized controlled trial with blind evaluation, 50 patients with osteoarthritis of the knee were allocated to a teriparatide treatment group (Forsteo, 20 µg daily for 2 months postoperatively) or to an untreated control group. RSA was performed postoperatively and at 6 months, 12 months, and 24 months. The primary effect variable was maximal total point motion (MTPM) from 12 to 24 months. Results - Median maximal total point motion from 12 to 24 months was similar in the 2 groups (teriparatide: 0.14 mm, 10% and 90% percentiles: 0.08 and 0.24; control: 0.13 mm, 10% and 90% percentiles: 0.09 and 0.21). [Authors: this is perhaps better than using "10th" and "90th", which looks ugly in print./language editor] The 95% confidence interval for the difference between group means was -0.03 to 0.04 mm, indicating that no difference occurred. Interpretation - We found no effect of teriparatide on migration in total knee replacement. Other trials using the same dosing have suggested a positive effect of teriparatide on human cancellous fracture healing. Thus, the lack of effect on migration may have been due to something other than the dose. In a similar study in this issue of Acta Orthopaedica, we found that migration could be reduced with denosumab (Ledin et al. 2017 ). The difference in response between the anabolic substance teriparatide and the antiresorptive denosumab suggests that resorption has a more important role during the postoperative course than any deficit in bone formation.

Effects of reactive oxygen species on the physical properties of polypropylene surgical mesh at various concentrations: a model for inflammatory reaction as a cause for mesh embrittlement and failure.

BACKGROUND: Oxidative degradation by reactive oxygen species (ROS) from inflammation initiates cross-linking, depolymerization, and formation of a quasi-crystalline quality in polypropylene (PP) meshes that cause embrittlement (J Urol 188:1052, 2012). Embrittlement leads to change in tensile strength and is associated with post-operative complications that include pain, adhesion, dislodgment, and fragmentation. METHODS: A laboratory environment was constructed to study the relationship between concentration of ROS and change in tensile strength. Samples of Ethicon Ultrapro© PP mesh were exposed to 1 mM, 0.1 M, or 1 M hydrogen peroxide solutions for 6 months and were subjected to load displacement tensile testing (LDTT) and compared to unexposed (0 M) meshes of the same brand. RESULTS: Load at failure and elongation to failure after LDTT were determined with 95 % confidence interval. For unexposed (0 M) samples, tensile strength was 28.0 ± 2.4 lbf and elongation to failure was 2.0 ± 0.3 in. For samples exposed to 1 mM, tensile strength was 19.2 ± 1.1 lbf and the elongation to failure was 2.0 ± 0.1 in. For samples exposed to 0.1 M, tensile strength was 19.3 ± 1.6 lbf and elongation to failure was 1.9 ± 0.1 in. For samples exposed to 1 M, tensile strength was 20.7 ± 1.2 lbf and elongation to failure was 0.47 ± 0.02 in. CONCLUSION: The results demonstrated that a 6-month exposure to a physiologic range of ROS (1 mM) decreased tensile strength of PP mesh by 31 %. 1 mM and 0.1 M samples behaved similarly demonstrating properties of a quasi-crystalline nature. 1 M samples displayed qualities of extreme embrittlement. Scanning electron microscopy (SEM) observed fiber changes. 1 M meshes had features of brittle materials. Knowledge of changes in physical properties of PP meshes is useful for considerations for the development of a more biocompatible surgical mesh.

Effects of teriparatide on cementless bipolar hemiarthroplasty in patients with osteoporotic femoral neck fractures.

BACKGROUND: For osteoporotic femoral neck fractures, suitable bone-implant stability is critical for pain relief, early return to daily activities and reduction of complications. Teriparatide (parathyroid hormone [PTH1-34]) can improve bone-implant stability in some basic studies. However it's use in osteoporotic femoral neck fractures treated by cementless hemiarthroplasties for the beneficial effects on bone-implant stability is sparse in the literature. The aim of this study was to determine if post-operative teriparatide administration can reduce femoral stem migration and improve early functional recovery and health-related quality of life (HRQoL). METHODS: Between 2010 and 2014, patients with osteoporotic femoral neck fracture who underwent cementless bipolar hemiarthroplasty were included into this retrospective cohort study. Group A included patients treated with cementless bipolar hemiarthroplasty only; Group B patients had additional teriparatide. Demographic data, complications, radiographic and functional outcomes as well as health-related quality of life (HRQoL) were compared. RESULTS: There were 52 hips in group A (no teriparatide) and 40 hips in group B (patient who received teriparatide). The subsidence of the femoral stem tended to be significantly decreased in the teriparatide group at 6 and 12 weeks post-operatively (p = 0.003 and p = 0.008, respectively). The Harris Hip Score (HHS) increased significantly from pre-operation to 6 weeks post-operatively and thereafter up to one year in both groups. However, there were no significant differences in terms of subsequent fracture, mortality, HHS, and HRQoL between two groups during the entire study period. CONCLUSIONS: Teriparatide significantly reduces the subsidence of the cementless femoral stem in elderly patients in the early post-operative period, but this benefit does not reflect better functional outcomes and HRQoL. Further prospective randomized large-scale cohort study is warranted for evidence-based recommendations.

Antibiotic cement was associated with half the risk of re-revision in 1,154 aseptic revision total knee arthroplasties.

BACKGROUND AND PURPOSE: Aseptic revisions comprise 80% of revision total knee arthroplasties (TKAs). We determined the incidence of re-revision TKA, the reasons for re-revision, and risk factors associated with these procedures. PATIENTS AND METHODS: We conducted a retrospective cohort study of 1,154 patients who underwent aseptic revision TKA between 2002 and 2013 and were followed prospectively by a total joint replacement registry in the USA. Revision was defined as any operation in which an implanted component was replaced. Patient-, surgeon-, and procedure-related risk factors were evaluated. Survival analyses were conducted. RESULTS: There were 114 re-revisions (10%) with a median time to reoperation of 3.6 years (interquartile range (IQR): 2.6-5.2). The infection rate was 2.9% (34/1,154) and accounted for 30% of re-revisions (34 of 114). In adjusted models, use of antibiotic-loaded cement was associated with a 50% lower risk of all-cause re-revision surgery (hazard ratio (HR) = 0.5, 95% CI: 0.3-0.9), age with a 20% lower risk for every 10-year increase (HR = 0.8, CI: 0.7-1.0), body mass index (BMI) with a 20% lower risk for every 5-unit increase (HR = 0.8, CI: 0.7-1.0), and a surgeon's greater cumulative experience (≥ 20 cases vs. < 20 cases) with a 3 times higher risk of re-revision (HR = 2.8, CI: 1.5-5). INTERPRETATION: Revised TKAs were at high risk of subsequent failure. The use of antibiotic-loaded cement, higher age, and higher BMI were associated with lower risk of further revision whereas a higher degree of surgeon experience was associated with higher risk.

Inhibitory effect of icariin on Ti-induced inflammatory osteoclastogenesis.

BACKGROUND: Wear particle-induced periprosthetic osteolysis that results in aseptic loosening is the most common cause of long-term failure after total joint replacement. MATERIALS AND METHODS: Icariin (ICA), a flavonoid isolated from Epimedium pubescens, inhibits osteoclast formation, but its effects on wear particle-induced inflammatory osteoclastogenesis remains unclear. We investigated the role of ICA in the regulation of osteoclast differentiation in a murine macrophage cell line (RAW264.7), which is stimulated by titanium (Ti) particles and the receptor activator of NF-κB ligand. RESULTS: ICA effectively inhibited osteoclast formation and bone resorption in the differentiation medium. ICA (10(-7) mol/L) significantly reduced the number of tartrate-resistant acid phosphatase-positive cells compared with the control, and significantly reduced the percentage of the surface covered by resorption lacunae. Quantitative real-time polymerase chain reaction analysis showed that ICA inhibited messenger RNA expression for the receptor activator of nuclear factor-κB, cathepsin K, tartrate-resistant acid phosphatase-positive, and matrix metalloproteinase-9 in RAW264.7 cells stimulated by Ti particles and receptor activator of NF-κB ligand. ICA also reduced pro-inflammatory cytokine expression of interleukin-1ß and tumor necrosis factor-α in RAW264.7 cells cultured with Ti particles. In addition, incubation with cholecystokinin-8 showed that ICA had no toxic effects on RAW264.7 cells. CONCLUSIONS: ICA possibly elicited inhibitory effects on inflammatory osteoclastogenesis induced by Ti particles, indicating that ICA may be useful for the prevention and treatment of wear particle-induced osteolysis.

Elimination of alpha-gal xenoreactive epitope: alpha-galactosidase treatment of porcine heart valves.

BACKGROUND AND AIM OF THE STUDY: Porcine heart valves are among the most widely used tissue valves in clinical heart valve implantation. However, immunologic responses have been implicated as potential causes of the limited durability of xenograft heart valves. The study aim was to determine the effectiveness of alpha-galactosidase treatment used to degrade the major xenoreactive antigens found in xenograft heart valves. METHODS: Fresh porcine heart valves and pericardium treated with alpha-galactosidase were studied to evaluate the xenoreactive galactose (alpha1,3) galactose (alpha-gal) antigen. Removal of the alpha-gal epitope from the porcine heart valve was monitored via 3,3'-diaminobenzidine staining intensity, while the removal of alpha-gal from N-glycans on porcine heart valves treated with recombinant alpha-galactosidase was determined either qualitatively or quantitatively by mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The porcine pericardium was used for monitoring the change in mechanical properties after alpha-galactosidase treatment. In addition, the biomechanical modification property of collagen fiber rearrangement on tissue was assessed using transmission electron microscopy (TEM). RESULTS: Following a 24-h incubation at pH 7.2, 4 degrees C, employing 0.1 U/ml of Bacteroides thetaiotaomicron-derived recombinant alpha-galactosidase, the enzyme effectively removed the alpha-gal epitopes expressed on porcine heart valves. The identification type of alpha-gal N-glycan on fresh aortic valve, aortic wall, pulmonary valve, and pulmonary wall was 7.1%, 10.3%, 6% and 8%, respectively. In the presence of alpha-galactosidase treatment, alpha-gal-containing N-glycans were converted into alpha-gal-negative N-glycans. Likewise, alpha-gal-containing N-glycans were not detected when MALDI-TOF MS quantitative analysis was used. Furthermore, no significant difference was observed in the mechanical properties and findings from TEM in alpha-galactosidase-treated porcine pericardial tissue when compared to fresh porcine pericardium. CONCLUSION: Alpha-galactosidase can effectively remove the alpha-gal epitope from porcine heart valves and pericardium. This may possibly alleviate harmful xenoreactive immunologic responses by alpha-gal, without adversely affecting the biomechanical properties of the alpha-galactosidase-processed tissue.