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.

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.

Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection.

Because of lipopolysaccharide (LPS)-mediated effects on osteoclast differentiation and bone loss, periprosthetic joint infection (PJI) caused by Gram-negative bacteria increases the risk of aseptic loosening after reimplantation. Synovial fluid interleukin-16 (IL-16) expression was higher in patients with PJI than in patients without joint infection. Thus, we explored the effects of IL-16 on bone. We investigated whether IL-16 modulates osteoclast or osteoblast differentiation in vitro. An LPS-induced bone loss mice model was used to explore the possible advantages of IL-16 inhibition for the prevention of bone loss. IL-16 directly activated p38 and c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) signaling and increased osteoclast activation markers, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, and nuclear factor of activated T cells 1 (NFATc1). IL-16 directly caused monocytes to differentiate into TRAP-positive osteoclast-like cells through NFATc1 activation dependent on JNK/MAPK signaling. Moreover, IL-16 did not alter alkaline phosphatase activity or calcium deposition during osteoblastic differentiation. Finally, IL-16 inhibition prevented LPS-induced trabecular bone loss and osteoclast activation in vivo. IL-16 directly increased osteoclast activation through the JNK/NFATc1 pathway. IL-16 inhibition could represent a new strategy for treating infection-associated bone loss.

Lipoteichoic Acid Accelerates Bone Healing by Enhancing Osteoblast Differentiation and Inhibiting Osteoclast Activation in a Mouse Model of Femoral Defects.

Lipoteichoic acid (LTA) is a cell wall component of Gram-positive bacteria. Limited data suggest that LTA is beneficial for bone regeneration in vitro. Thus, we used a mouse model of femoral defects to explore the effects of LTA on bone healing in vivo. Micro-computed tomography analysis and double-fluorochrome labeling were utilized to examine whether LTA can accelerate dynamic bone formation in vivo. The effects of LTA on osteoblastogenesis and osteoclastogenesis were also studied in vitro. LTA treatment induced prompt bone bridge formation, rapid endochondral ossification, and accelerated healing of fractures in mice with femoral bone defects. In vitro, LTA directly enhanced indicators of osteogenic factor-induced MC3T3-E1 cell differentiation, including alkaline phosphatase activity, calcium deposition and osteopontin expression. LTA also inhibited osteoclast activation induced by receptor activator of nuclear factor-kappa B ligand. We identified six molecules that may be associated with LTA-accelerated bone healing: monocyte chemoattractant protein 1, chemokine (C-X-C motif) ligand 1, cystatin C, growth/differentiation factor 15, endostatin and neutrophil gelatinase-associated lipocalin. Finally, double-fluorochrome, dynamic-labeling data indicated that LTA significantly enhanced bone-formation rates in vivo. In conclusion, our findings suggest that LTA has promising bone-regeneration properties.

Augmentative antirotational plating provided a significantly higher union rate than exchanging reamed nailing in treatment for femoral shaft aseptic atrophic nonunion - retrospective cohort study.

BACKGROUND: Atrophic nonunion of femoral shaft fracture after intramedullary (IM) nailing is uncommon. The treatment for femoral shaft aseptic atrophic non-union remained controversial. The aim of this study was to compare the surgical results between exchanging reamed nailing (ERN) and augmentative antirotational plating (AAP) for femoral shaft aseptic atrophic nonunion. METHODS: We retrospectively reviewed the patients with femoral shaft nonunion between the year of 2014 and 2015. The patients with nonunion after plate osteosynthesis, septic nonunion, hypertrophic nonunion, additional surgery during revision surgery were excluded. All the patients were followed up at least 12 months. RESULTS: Overall, the union rate after revision surgery was 70.8%. The union rate was significantly higher in the AAP group than in the ERN group. Operating time was also significantly shorter in the AAP group. Regarding the location of nonunion, the union rate was comparable between groups for isthmic nonunions. However, for non-isthmic nonunions, the union rate was significantly higher and operating time was significantly shorter in the AAP group. CONCLUSION: AAP showed an overall higher union rate for management of femoral shaft aseptic atrophic nonunion compared with ERN. Especially for non-isthmic femoral shaft atrophic nonunions, AAP provided a significantly higher union rate and significantly shorter operating time.

Real-time detection of antibiotics cytotoxicity in rabbit periosteal cells using microfluidic devices with comparison to conventional culture assays.

BACKGROUND: Local antibiotic application has been widely used in orthopedic surgery. The dose-related toxicity of antibiotics towards periosteal tissues and resulting effects on osteogenic expression are yet to be studied. METHODS: Periosteal cells harvested from the medial tibia of New Zealand White rabbits were used. A seeding density of 5 × 103 cells/cm2 was determined to be optimal for testing in the pilot study; the cells were cultured in xCELLigence 96-well plates. Microfluidic impedance analyzers were used to monitor cellular proliferation in microfluidic culture systems with exposure to three different concentrations (10 µg/mL, 100 µg/mL, and 1000 µg/mL) of cefazolin, ciprofloxacin, and vancomycin, respectively. The correlation of cell index at day 7 with optical density values from WST-1 assays using conventional cultures was evaluated by calculating the Pearson's coefficient. RNA analysis was performed to investigate the expression of osteogenic markers in the cultured cells, including core-binding factor alpha 1 (Cbfa1), osteopontin (OPN), and osteopontin promoter (OPNp), relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as the endogenous control. RESULTS: A significant dose-related inhibition of cell index was found for all the 3 antibiotics, whereas the WST-1 assays showed a significant dose-related inhibition of cellular proliferation only at a high dose of cefazolin (1000 µg/mL) and medium-to-high dose of ciprofloxacin (100 µg/mL and 1000 µg/mL). Pearson's coefficient analysis indicated a high correlation between the cell index and optical density values of WST-1 assays only for medium and high doses of ciprofloxacin (100 µg/mL and 1000 µg/mL); a moderate correlation was seen for cefazolin, and a low dose of ciprofloxacin (10 µg/mL). RNA analysis confirmed significant dose-related inhibition of cfba1, OPN, and OPNp expression by all three antibiotics. CONCLUSION: With optimal seeding amounts, rabbit periosteal cells can be dynamically monitored in the xCELLigence microfluidic system. Dose-related inhibition of cellular proliferation and osteogenic expression was found after exposure to cefazolin and ciprofloxacin. By providing real-time detection and exhibiting comparable correlation, microfluidic impedance-based analyzer is a feasible alternative to the conventional WST-1 assays.

Sustained relief of pain from osteosynthesis surgery of rib fracture by using biodegradable lidocaine-eluting nanofibrous membranes.

Various effective methods are available for perioperative pain control in osteosynthesis surgery, but they are seldom applied intraoperatively. The aim of this study was to evaluate a biodegradable poly([d,l]-lactide-co-glycolide) (PLGA)/lidocaine nanofibrous membrane for perioperative pain control in rib fracture surgery. Scanning electron microscopy showed high porosity of the membrane, and an ex vivo high-performance liquid chromatography study revealed an excellent release profile for both burst and controlled release of lidocaine within 30days. Additionally, the PLGA/lidocaine nanofibrous membrane was applied in an experimental rabbit rib osteotomy model. Implantation of the membrane around the osteotomized rib during osteosynthesis surgery resulted in a significant increase in weight gain, food and water consumption, and daily activity compared to the study group without the membrane. In addition, all osteotomized ribs were united. Thus, application of the PLGA/lidocaine nanofibrous membrane may be effective for sustained relief of pain in oeteosynthesis surgery.

Topical tranexamic acid reduces blood loss and transfusion rates associated with primary total hip arthroplasty.

BACKGROUND: Systemic tranexamic acid can decrease blood loss and rates of transfusion in patients undergoing total hip arthroplasty (THA). However, the efficacy of topical tranexamic acid in THA has only recently been characterized in a small number of studies. QUESTIONS/PURPOSES: The purpose of this study was to compare (1) the greatest hemoglobin decrease after surgery; (2) transfusion rates; and (3) symptomatic thromboembolic events among patients undergoing THA who did and did not receive topical tranexamic acid. METHODS: We retrospectively compared 135 patients (154 THAs) who received 10 mL 5% tranexamic acid added in a topical cocktail solution during surgery between January 2009 and July 2011 with 211 patients (234 THAs) who received only the topical cocktail solution (analgesic and antibiotic agent) between January 2005 and December 2008. Contraindications for the use of tranexamic acid included a documented history of a venous thromboembolic event, an allergy to tranexamic acid, thrombophilia, or a high risk of venous thromboembolism based on the guidelines of the American Academy of Orthopaedic Surgeons; the 135 patients who received it during that period represented 99.4% of the patients undergoing THA during that time. We compared changes in Hb, transfusion rates, estimated blood loss, surgical results, and complications between the groups. The transfusion threshold was the same, when the Hb values were < 10 g/dL. Patients were screened for thromboembolic disease if symptoms or signs appeared. RESULTS: Hb decreased less in the tranexamic acid group (1.87 ± 1.10 g/dL) than in the control group (2.2 ± 1.36 g/dL; p = 0.01) on the first postoperative day. The frequency of transfusion was lower in patients receiving tranexamic acid (17% as compared with 35% in the control group; p < 0.001). There was only one nonfatal pulmonary embolism in the control group during the study period. CONCLUSIONS: Use of topical tranexamic acid in patients undergoing THA reduces postoperative bleeding and decreases blood transfusion rates. No increase in major complications was identified in patients managed with topical tranexamic acid. This retrospective study confirms the results of a smaller randomized trial on the same topic by another group. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Development of a Biodegradable PLGA Carrier to Provide Wnt Agonists and Antibiotics to Meet the Requirements for Patients with Bone Infections.

Antibiotic beads can be used to treat surgical infections. In this study, polylactide-polyglycolide (PLGA) was mixed with vancomycin, the osteogenic enhancer lithium chloride (LiCl), and hot compression to form PLGA-vancomycin-LiCl delivery beads to treat bone infection. An elution method was used to characterize in vitro release characteristics of vancomycin and Li over a 42-day period. The release profiles lasted for more than 42 days for vancomycin and 28 days for Li. The concentration of vancomycin in each sample was well above the breakpoint sensitivity. Lithium cotreatment enhanced the bactericidal effect of vancomycin. Released Li and vancomycin increased the mRNA or protein expressions of osteogenic markers of mesenchymal stem cells (MSCs). In vivo, the PLGA delivery systems were implanted into the distal femoral cavities of rabbits, and the cavity fluid content was aspirated and analyzed at each time point. The released Li and vancomycin lasted more than 6 weeks, and the vancomycin concentrations were much greater than the breakpoint sensitivity. Four rabbits in each group were sacrificed at 8 weeks for histological observation. More mature bone tissue was observed in the Li treatment group. This study provides a PLGA drug delivery system to meet the requirements of patients with bone infections.

What is the success of treatment of hip and knee candidal periprosthetic joint infection?

BACKGROUND: Fungal infection at an arthroplasty site is rare and poses a therapeutic challenge. To the best of our knowledge, no reports have been published thus far on the success rate of prosthesis reimplantation after fungal prosthetic joint infections. QUESTIONS/PURPOSES: We asked: (1) What is the success rate in terms of infection eradication using a two-stage exchange arthroplasty in patients with hip or knee fungal periprosthetic joint infections, particularly focusing on Candida infections? (2) What patient-, infection-, and treatment-related variables are associated with the success or failure of treatment? METHODS: From January 2000 to December 2010, 16 patients with hip or knee candidal periprosthetic joint infections were treated with two-stage exchange arthroplasty at our institute. Treatment success was defined as a well-functioning joint without relapse of candidal infection after prosthesis reimplantation, while treatment failure was defined as uncontrolled or relapse of candidal infection or mortality. Variables, including age, sex, comorbidities, microbiology, antimicrobial agents used, and operative methods, were analyzed. Minimum followup was 28 months (mean, 41 months; range, 28-90 months). RESULTS: At latest followup, the treatment failed to eradicate the infection in eight of the 16 patients, and there were four deaths related to fungemia. Four patients required permanent resection arthroplasty owing to uncontrolled or recurrent candidal infections. All eight patients (50% successful rate) who had their infections eradicated and successful prosthesis reimplantation had prolonged treatment with oral fluconazole before (mean, 8 months) and after (mean, 2.2 months) prosthesis reimplantation. The antifungal therapy correlated with successful treatment. Renal insufficiency, hypoalbuminemia, anemia, and chronic obstructive pulmonary disease were significantly more prevalent in the treatment-failure group than in the treatment-success group. CONCLUSIONS: Half of the patients treated with two-stage exchange arthroplasty for fungal periprosthetic joint infections had recurrence or lack of control of the infection. A prolonged antifungal therapy appeared to be essential for successful treatment of candidal periprosthetic joint infections. The presence of renal insufficiency, hypoalbuminemia, anemia, or chronic obstructive pulmonary disease might be associated with a poor outcome.

The influence of storage temperature on the antibiotic release of vancomycin-loaded polymethylmethacrylate.

Periprosthetic joint infection is devastating and increases medical expenditure and socioeconomic burden. Antibiotic-loaded cement spacer is useful in the interim period before the reimplantation surgery. Prefabricated antibiotic-loaded cement spacers can decrease operation time but have been limitedly used clinically. In the literature, there is no clear recommendation on the storage temperature for the prefabricated cement spacers. We used an in vitro model to analyze whether the storage temperature at 25°C, 4°C, or -20°C for 2 weeks or 3 months could affect the release of vancomycin from the cement. We found that the storage temperature and time had no significant effects on the pattern and amount of vancomycin release. The patterns of vancomycin release from the cement stored at different temperatures were similar with an abrupt release in the first 3 days and steadily declined in the following period. This study provides a preliminary result to justify the storage of fabricating antibiotic-loaded cement spacer sterilely packed at room temperature. Further studies to examine the effects of storage temperature on the mechanical strength and the release pattern of other antibiotics should be done to provide more evidence to support the clinical use of prefabricated ready-to-use antibiotic-loaded cement spacer.

Molecular diagnosis of periprosthetic joint infection by quantitative RT-PCR of bacterial 16S ribosomal RNA.

The diagnosis of periprosthetic joint infection is sometimes straightforward with purulent discharge from the fistula tract communicating to the joint prosthesis. However it is often difficult to differentiate septic from aseptic loosening of prosthesis because of the high culture-negative rates in conventional microbiologic culture. This study used quantitative reverse transcription polymerase chain reaction (RT-qPCR) to amplify bacterial 16S ribosomal RNA in vitro and in 11 clinical samples. The in vitro analysis demonstrated that the RT-qPCR method was highly sensitive with the detection limit of bacterial 16S rRNA being 0.148 pg/ µ l. Clinical specimens were analyzed using the same protocol. The RT-qPCR was positive for bacterial detection in 8 culture-positive cases (including aerobic, anaerobic, and mycobacteria) and 2 culture-negative cases. It was negative in one case that the final diagnosis was confirmed without infection. The molecular diagnosis of bacterial infection using RT-qPCR to detect bacterial 16S rRNA around a prosthesis correlated well with the clinical findings. Based on the promising clinical results, we were attempting to differentiate bacterial species or drug-resistant strains by using species-specific primers and to detect the persistence of bacteria during the interim period before the second stage reimplantation in a larger scale of clinical subjects.

The role of EDIL3 in maintaining cartilage extracellular matrix and inhibiting osteoarthritis development.

Aims: Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown. Methods: We used human cartilage plugs (ex vivo) and mice with spontaneous OA (in vivo) to explore whether EDIL3 has a chondroprotective effect by altering OA-related indicators. Results: EDIL3 protein prevented chondrocyte clustering and maintained chondrocyte number and SOX9 expression in the human cartilage plug. Administration of EDIL3 protein prevented OA progression in STR/ort mice by maintaining the number of chondrocytes in the hyaline cartilage and the number of matrix-producing chondrocytes (MPCs). It reduced the degradation of aggrecan, the expression of matrix metalloproteinase (MMP)-13, the Osteoarthritis Research Society International (OARSI) score, and bone remodelling. It increased the porosity of the subchondral bone plate. Administration of an EDIL3 antibody increased the number of matrix-non-producing chondrocytes (MNCs) in cartilage and exacerbated the serum concentrations of OA-related pro-inflammatory cytokines, including monocyte chemotactic protein-3 (MCP-3), RANTES, interleukin (IL)-17A, IL-22, and GROα. Administration of ß1 and ß3 integrin agonists (CD98 protein) increased the expression of SOX9 in OA mice. Hence, EDIL3 might activate ß1 and ß3 integrins for chondroprotection. EDIL3 may also protect cartilage by attenuating the expression of IL-1ß-enhanced phosphokinase proteins in chondrocytes, especially glycogen synthase kinase 3 alpha/beta (GSK-3α/ß) and phospholipase C gamma 1 (PLC-γ1). Conclusion: EDIL3 has a role in maintaining the cartilage ECM and inhibiting the development of OA, making it a potential therapeutic drug for OA.

Characterization and Advancement of an Evaluation Method for the Treatment of Spontaneous Osteoarthritis in STR/ort Mice: GRGDS Peptides as a Potential Treatment for Osteoarthritis.

STR/ort mice spontaneously exhibit the typical osteoarthritis (OA) phenotype. However, studies describing the relationship between cartilage histology, epiphyseal trabecular bone, and age are lacking. We aimed to evaluate the typical OA markers and quantify the subchondral bone trabecular parameters in STR/ort male mice at different weeks of age. We then developed an evaluation model for OA treatment. We graded the knee cartilage damage using the Osteoarthritis Research Society International (OARSI) score in STR/ort male mice with or without GRGDS treatment. We measured the levels of typical OA markers, including aggrecan fragments, matrix metallopeptidase-13 (MMP-13), collagen type X alpha 1 chain (COL10A1), and SRY-box transcription factor 9 (Sox9), and quantified epiphyseal trabecular parameters. Compared to the young age group, elderly mice showed an increased OARSI score, decreased chondrocyte columns of the growth plate, elevated expression of OA markers (aggrecan fragments, MMP13, and COL10A1), and decreased expression of Sox9 at the articular cartilage region in elderly STR/ort mice. Aging also significantly enhanced the subchondral bone remodeling and microstructure change in the tibial plateau. Moreover, GRGDS treatment mitigated these subchondral abnormalities. Our study presents suitable evaluation methods to characterize and measure the efficacy of cartilage damage treatments in STR/ort mice with spontaneous OA.

Effects of Hyperbaric Oxygen Intervention on the Degenerated Intervertebral Disc: From Molecular Mechanisms to Animal Models.

MicroRNA (miRNA) 107 expression is downregulated but Wnt3a protein and ß-catenin are upregulated in degenerated intervertebral disc (IVD). We investigated mir-107/Wnt3a-ß-catenin signaling in vitro and in vivo following hyperbaric oxygen (HBO) intervention. Our results showed 96 miRNAs were upregulated and 66 downregulated in degenerated nucleus pulposus cells (NPCs) following HBO treatment. The 3' untranslated region (UTR) of the Wnt3a mRNA contained the "seed-matched-sequence" for miR-107. MiR-107 was upregulated and a marked suppression of Wnt3a was observed simultaneously in degenerated NPCs following HBO intervention. Knockdown of miR-107 upregulated Wnt3a expression in hyperoxic cells. HBO downregulated the protein expression of Wnt3a, phosphorylated LRP6, and cyclin D1. There was decreased TOP flash activity following HBO intervention, whereas the FOP flash activity was not affected. HBO decreased the nuclear translocation of ß-catenin and decreased the secretion of MMP-3 and -9 in degenerated NPCs. Moreover, rabbit serum KS levels and the stained area for Wnt3a and ß-catenin in repaired cartilage tended to be lower in the HBO group. We observed that HBO inhibits Wnt3a/ß-catenin signaling-related pathways by upregulating miR-107 expression in degenerated NPCs. HBO may play a protective role against IVD degeneration and could be used as a future therapeutic treatment.

Antibacterial activity of joint fluid in cemented total-knee arthroplasty: an in vivo comparative study of polymethylmethacrylate with and without antibiotic loading.

The objective of this study was to evaluate the antibacterial activities of joint fluids of patients undergoing total-knee arthroplasty (TKA). Thirty patients who were scheduled for primary cemented TKA were enrolled in the study. The patients were grouped on the basis of whether the cement was without antibiotic loading (control group) or loaded with oxacillin (oxacillin group) or vancomycin (vancomycin group). Cefazolin was administered to every patient as the perioperative prophylactic antibiotic. Samples of joint fluids were collected from the knee joints at 8, 16, 24, 32, 40, and 48 h after prosthesis implantation. We assessed the bioactivities of the joint fluids against methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA). The antibiotic contents of the joint fluid samples were further evaluated by using high-performance liquid chromatography. Against MSSA, all joint fluid samples exhibited at least 24 h of bacterial inhibition activity. The oxacillin (43.2 h ± 2 h) and vancomycin (40.8 h ± 1.8 h) groups exhibited significantly longer durations of antibacterial activities than the control group (28 h ± 1.3 h; P < 0.05). However, antibacterial activity against MRSA was observed only in the vancomycin group. In conclusion, cefazolin, which was administered as a prophylactic antibiotic in TKA, exhibited good ability for knee joint penetration and was sufficient to inhibit MSSA during its administration. The use of antibiotic-loaded cement can prolong the antibacterial activity of joint fluid in TKA. Further, vancomycin-loaded cement had antibacterial activity against MRSA superior to that of cement loaded with oxacillin or without antibiotic loading.

Acute delirium and poor compliance in total hip arthroplasty patients with substance abuse disorders.

From the joint registry of 2831 primary total hip arthroplasties (2351 patients) performed between 1998 and 2003, we identified 15 patients (16 hips) who had a documented history of substance abuse disorders at the time of the index surgery. The patients included 13 men (14 hips) and 2 women (2 hips), with the mean age of 49 years (range, 29-65 years). On the basis of the criteria specified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, 13 patients had alcohol abuse disorders, 1 had amphetamine abuse disorder, and 1 had heroin abuse disorder. We found high rates of postoperative substance withdrawal delirium and psychosis (46%), late complication (25%), and lost to follow-up (27%) in these patients. Because patients with substance abuse disorders have unexpected perioperative psychotic episodes, poor compliance, and a tendency to not follow medical advice after surgery and show early discontinuation of follow-up, we suggest that surgeons should work with other medical professionals and carefully perform total hip arthroplasty in such patients.

Pain distribution and response to total hip arthroplasty: a prospective observational study in 113 patients with end-stage hip disease.

PURPOSE: The aim of this study was to investigate the pain patterns in patients with end-stage hip disease and to assess the response after total hip arthroplasty (THA). METHODS: The pain patterns of patients undergoing THA for end-stage hip diseases were prospectively evaluated by requesting them to mark a map of body areas before and after surgery. Patients were excluded if they had coexisting pathology of the knee or spine. The pain measurements were quantified using visual analog scales, and factors that may contribute to different pain patterns were also evaluated. RESULTS: Among 113 patients (113 hips) enrolled in the study, the groin, anterior thigh, buttock, anterior knee, and greater trochanter were the most common pain locations before THA. Pain over the lower back, shin, and calf areas, which were not generally considered referral pain areas from hip diseases, was present in 21.2, 7.1, and 2.7% patients, respectively. The presence of lower back pain (LBP) was statistically more common in patients with longer duration of hip symptoms. Regardless of the different pain patterns, 97.3% (110 of 113) of patients reported complete pain relief within 12 weeks after THA. CONCLUSIONS: The distribution of pain from end-stage hip diseases is versatile, and presence of pain in areas other than around the hip is not uncommon. LBP was more common in patients with longer duration of symptoms. THA satisfactorily resolves the pain in all areas soon after surgery.

Nontuberculous mycobacteria peri-prosthetic joint infection: An outcome analysis for two stage revision arthroplasty.

PURPOSE: Nontuberculous mycobacteria periprosthetic joint infection (NTMPJI) is a rare complication of hip or knee joint arthroplasty. The experience for outcomes of NTMPJI treatment is still limited. The objective of this study was to investigate the outcome of hip or knee nontuberculous mycobacteria periprosthetic joint infection following treatment with two-stage exchange arthroplasty. MATERIAL AND METHODS: From 1995 to 2020, 12 patients with NTMPJI were treated with two-stage exchange arthroplasty at our institution. We collected and analyzed variables including demographic data, comorbidity, microbiological data, treatment outcome and antibiotic formula in bone cement. RESULTS: Mycobacterium abcessus (n = 6) and Mycobacterium chelonae (n = 2) constitute the majority of the cases. Five patients had early-onset PJIs and the other seven patients were late onset. The success rate of two-stage exchange arthroplasty was 66.7% (8 of 12). Three patients experienced infection relapse, and one patient had soft tissue compromise complication. Post-operative antibiotic therapy may not improve the success rate (4 of 6 cases, 66.7%). Based on in vitro study, the most commonly used effective antibiotic in bone cement spacer for nontuberculous mycobacteria was amikacin. CONCLUSIONS: nontuberculous mycobacteria is a rare cause of PJIs and should be suspected especially in relatively immunocompromised patients. Resection arthroplasty with staged reimplantation is the preferred approach. Prolonged post-operative antibiotic therapy before reimplantation may not improve the success rate. Delayed revision surgery may not be needed and can be performed once C-reactive protein level is normal after a drug holiday.

In vitro activities of daptomycin-, vancomycin-, and teicoplanin-loaded polymethylmethacrylate against methicillin-susceptible, methicillin-resistant, and vancomycin-intermediate strains of Staphylococcus aureus.

The objective of this study was to evaluate the antibacterial effects of polymethylmethacrylate (PMMA) bone cements loaded with daptomycin, vancomycin, and teicoplanin against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-intermediate Staphylococcus aureus (VISA) strains. Standardized cement specimens made from 40 g PMMA loaded with 1 g (low-dose), 4 g (middle-dose) or 8 g (high-dose) antibiotics were tested for elution characteristics and antibacterial activities. The patterns of release of antibiotics from the cement specimens were evaluated using in vitro broth elution assay with high-performance liquid chromatography. The activities of broth elution fluid against different Staphylococcus aureus strains (MSSA, MRSA, and VISA) were then determined. The antibacterial activities of all the tested antibiotics were maintained after being mixed with PMMA. The cements loaded with higher dosages of antibiotics showed longer elution periods. Regardless of the antibiotic loading dose, the teicoplanin-loaded cements showed better elution efficacy and provided longer inhibitory periods against MSSA, MRSA, and VISA than cements loaded with the same dose of vancomycin or daptomycin. Regarding the choice of antibiotics for cement loading in the treatment of Staphylococcus aureus infection, teicoplanin was superior in terms of antibacterial effects.