Abstract:
BACKGROUND:The innate immune system can recall previous immunologic challenges and thus respond more effectively to subsequent unrelated challenges, a phenomenon called trained immunity. Training the innate immune system before surgery might be a potential option to prevent bone and joint infection. QUESTIONS/PURPOSES:(1) Does the training process cause adverse effects such as fever or organ injury? (2) Does training the innate immune system confer broad-spectrum protection against bone and joint infection in a mouse model? (3) Does trained immunity remain effective for up to 8 weeks in this mouse model? METHODS:After randomization and group information blinding, we trained the innate immune system of C57BL/6 mice (n = 20 for each group) by intravenously injecting them with either 0.1 mg of zymosan (a toll-like receptor 2 agonist), 0.1 mg of lipopolysaccharide (a toll-like receptor 4 agonist), or normal saline (control). For assessing the host response and possible organ injury after training and infection challenge, we monitored rectal temperature, collected blood to determine leukocyte counts, and performed biochemical and proinflammatory cytokine analyses. After 2 weeks, we then assessed whether trained immunity could prevent infections in an intraarticular implant model subjected to a local or systemic challenge with a broad spectrum of bacterial species (Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Streptococcus pyogenes, or Pseudomonas aeruginosa) in terms of culture-positive rate and colony counts. The proportion of culture-positive joint samples from trained and control groups were compared after 4 weeks. Finally, we increased the interval between training and bacterial challenge up to 8 weeks to assess the durability of training efficacies. RESULTS:Training with zymosan and lipopolysaccharide caused mild and transient stress in host animals in terms of elevated rectal temperature and higher blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase levels. Trained mice had fewer culture-positive joint samples after local inoculation with S. aureus (control: 100% [20 of 20]; zymosan: 55% [11 of 20], relative risk 0.55 [95% CI 0.37 to 0.82]; p = 0.001; lipopolysaccharide: 60% [12 of 20], RR 0.60 [95% CI 0.42 to 0.86]; p = 0.003) and systemic challenge with S. aureus (control: 70% [14 of 20]; zymosan: 15% [3 of 20], RR 0.21 [95% CI 0.07 to 0.63]; p = 0.001; lipopolysaccharide: 15% [3 of 20], RR 0.21 [95% CI 0.07 to 0.63]; p = 0.001) than controls. We observed similar patterns of enhanced protection against local and systemic challenge of E. coli, E. faecalis, S. pyogenes, and P. aeruginosa. Zymosan-trained mice were more effectively protected against both local (control: 20 of 20 [100%], zymosan: 14 of 20 [70%], RR 0.70 [95% CI 0.53 to 0.93]; p = 0.02) and systemic (control: 70% [14 of 20]; zymosan: 30% [6 of 20], RR 0.43 [95% CI 0.21 to 0.89]; p = 0.03) challenge with S. aureus for up to 8 weeks than controls. CONCLUSIONS:Trained immunity confers mild stress and broad-spectrum protection against bone and joint infection in a mouse model. The protection conferred by immunity training lasted up to 8 weeks in this mouse model. The results of the current research support further study of this presurgical strategy to mitigate bone and joint infection in other large animal models. CLINICAL RELEVANCE:If large animal models substantiate the efficacy and safety of presurgical immunity training-based strategies, clinical trials would be then warranted to translate this strategy into clinical practice.
journal_name
Clin Orthop Relat Resjournal_title
Clinical orthopaedics and related researchauthors
Zhu H,Lin J,Wei H,Bao B,Gao T,Zheng Xdoi
10.1097/CORR.0000000000001461subject
Has Abstractpub_date
2020-11-01 00:00:00pages
2670-2681issue
11eissn
0009-921Xissn
1528-1132journal_volume
478pub_type
杂志文章abstract::One hundred consecutive unicondylar knee arthroplasties were reviewed after eight to 12 years of follow-up evaluation. Eighteen patients (19 knees) had died, four patients (four knees) were lost to follow-up evaluation, and 13 patients (13 knees) had revision. Survivorship analysis revealed 90% survivorship of the pro...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract:BACKGROUND:Outcomes after intrasynovial tendon repair are highly variable. An intense inflammatory cascade followed by a delayed healing response can cause adhesion formation and repair-site failure that severely impair the function of repaired digits. No effective remedies exist to fully address these issues. Cell- an...
journal_title:Clinical orthopaedics and related research
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journal_title:Clinical orthopaedics and related research
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journal_title:Clinical orthopaedics and related research
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doi:10.1097/00003086-199808000-00018
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abstract:BACKGROUND:As in all fields of medicine, animal studies are widely performed in orthopaedics and have increased in number over time. However, it is not clear to what extent these studies provide a basis for future research or advancements in clinical science. Concerns about the reliability and translational ability of ...
journal_title:Clinical orthopaedics and related research
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journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1976-11-01 00:00:00
abstract::We report the case of an infected nonunion of the proximal femoral in an elderly patient. There was extensive involvement of the entire proximal femur precluding salvage. An impromptu use of a cephalomedullary nail coated with antibiotic-laden bone cement is described, followed by reimplantation with a revision-type p...
journal_title:Clinical orthopaedics and related research
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journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
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更新日期:1997-11-01 00:00:00
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journal_title:Clinical orthopaedics and related research
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journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
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更新日期:1980-05-01 00:00:00
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journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
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更新日期:1993-11-01 00:00:00
abstract::A stylized wedge-shaped defect was created in the medial plateau of autopsy specimens of the tibia to evaluate methods for fixation in total knee arthroplasty. A series of tibial components was inserted by five different methods. With each method loading of up to 1780 N axially and a varus load of 1340 N at 28 Newton-...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1984-04-01 00:00:00
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journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
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journal_title:Clinical orthopaedics and related research
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journal_title:Clinical orthopaedics and related research
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更新日期:2001-02-01 00:00:00
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journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章,评审
doi:10.1097/00003086-200209000-00004
更新日期:2002-09-01 00:00:00
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journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1097/01.blo.0000150465.29883.83
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journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1993-10-01 00:00:00
abstract::Sixty-six cases of noninfected nonunions (27 femoral and 39 tibial) were treated with an interlocking nail. In these cases, 92.6% of the femurs and 94.8% of the tibias healed after the first operation in a mean time of 15.4 and 13.0 weeks, respectively. Deep infection complicated five nailings (7.5%, two femur and thr...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1986-11-01 00:00:00
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journal_title:Clinical orthopaedics and related research
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journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
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journal_title:Clinical orthopaedics and related research
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doi:
更新日期:1982-11-01 00:00:00
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journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
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journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1978-06-01 00:00:00
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journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章,评审
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更新日期:2003-06-01 00:00:00
abstract::The bone mineral content in the shafts of the forearm in 17 women with cervical fracture of the upper end of the femur was low. The cortex of the femoral neck was also lower than normal. Thus women with hip fractures at an early age may have lower than average total skeletal tissue density. This may be due not simply ...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1977-05-01 00:00:00
abstract::Between 1977 and 1982, 19 cases of congenital dislocation of the hip (CDH) were encountered in black infants. Six of these cases were associated with other anomalies (atypical CDH); 13 were typical CDH. The incidence of complete CDH in the white population studied is 1.5/1000; in the black population studied it is 0.4...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::A series of patients with single major scoliosis curvatures attributable to spina bifida treated by anterior only spinal fusion was studied for 2 years to determine whether the infection rate could be decreased, adequate correction and pelvic balance could be provided, and posterior surgery could be avoided in these p...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1097/00003086-199907000-00016
更新日期:1999-07-01 00:00:00
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journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1007/s11999-014-4115-7
更新日期:2015-04-01 00:00:00
abstract::In 31 children with osteoid osteoma lesions about the hip ranging in age from 2 to 16 years, there was an inordinate frequency of diagnostic delay with 16 patients having symptoms for more than 12 months. The clinical features were dominated by pain, limp, restricted hip motion and thigh atrophy. Twelve patients did n...
journal_title:Clinical orthopaedics and related research
pub_type: 杂志文章
doi:10.1097/00003086-197501000-00006
更新日期:1975-01-01 00:00:00