RESUMO
BACKGROUND: This study aimed to: 1) compare treatment outcomes between debridement, antibiotics, and implant retention (DAIR) and partial or complete revision arthroplasty (RA) for early postoperative and acute hematogenous total hip arthroplasty periprosthetic joint infection (PJI) and 2) identify factors associated with treatment outcome. METHODS: The study consisted of a retrospective cohort of patients who underwent surgery for PJI between 2004 and 2021. There were 76 patients (74.5%) who underwent DAIR and 26 patients (25.5%) who underwent RA. Treatment success was defined as treatment eradication at a minimum of a 2-year follow up. Bivariate regression analysis was used to assess the effect of different factors on treatment outcomes. Kaplan-Meier survivorship was performed to compare survivorship between cohorts. RESULTS: At a mean follow-up of 8.2 years (range, 2.2 to 16.4), significantly more DAIR failed treatment (DAIR, 50 [65.8%]; 10 [38.5%]; P = .015). The 8-year Kaplan-Meier survivorship was 35.1% [95% confidence interval (CI), 24.3 to 45.9] for patients treated with DAIR and 61.5% [95% CI, 42.9 to 80.1] for those treated with RA (log rank = 0.039). Bivariate regression analysis showed performing a RA was associated with a higher likelihood of treatment success (odds ratio 4.499, 95% CI 1.600 to 12.647, P = .004), whereas a higher body mass index was associated with treatment failure (odds ratio 0.934, 95% CI 0.878 to 0.994, P = .032). CONCLUSIONS: To reduce the rate of recalcitrant infection following early postoperative or acute hematogenous total hip arthroplasty PJI, RA may be of benefit over DAIR. This is especially relevant in the early postoperative period, when components can be readily exchanged.
Assuntos
Antibacterianos , Artroplastia de Quadril , Desbridamento , Prótese de Quadril , Infecções Relacionadas à Prótese , Reoperação , Humanos , Infecções Relacionadas à Prótese/cirurgia , Infecções Relacionadas à Prótese/etiologia , Artroplastia de Quadril/efeitos adversos , Masculino , Feminino , Reoperação/estatística & dados numéricos , Idoso , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Prótese de Quadril/efeitos adversos , Resultado do Tratamento , Idoso de 80 Anos ou mais , Retenção da Prótese , SeguimentosRESUMO
Background: The most effective surgical approach to total hip replacement (THR) remains controversial. Most studies that have compared approaches have reported only short-term outcome data. It is therefore unclear in the literature if a particular surgical approach offers long-term advantages. The aim of this study was to determine the effect of the 3 main surgical approaches to THR on patient-reported outcomes 5 years after surgery. Methods: All patients who underwent a THR for osteoarthritis or osteonecrosis between 2008 and 2012 by an anterior, posterior or lateral approach at The Ottawa Hospital in Ontario, Canada, were included in the study. All preoperative and postoperative scores for the Hip Disability and Osteoarthritis Outcome Score (HOOS) and Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC) questionnaires were recorded. Analysis of covariance was used to study the relationship between the amount of change in scores on the HOOS and WOMAC subscales (dependent variables) and the surgical approach. The confounding factors of age, sex, American Society of Anesthesiologists (ASA) class, Charnley classification and body mass index were included in the analysis. Results: There were 138 patients (37.6%) in the posterior approach group, 104 (28.3%) in the lateral approach group and 125 (34.1%) in the anterior approach group. There were no significant differences among the 3 groups in terms of Charnley classification, body mass index, sex, ASA class, surgical side and preoperative functional scores. We did not observe any significant differences in the amount of change in the scores for HOOS and WOMAC subscales among the 3 groups. There were also no differences in the final postoperative scores. Conclusion: Our findings suggest that the choice of surgical approach in primary THR surgery without revision has no influence on functional outcomes and quality of life after 5 years. Further studies are needed to assess how patient age and sex may influence the functional outcome of individual surgical approaches.
Contexte: L'approche chirurgicale la plus efficace pour l'arthroplastie totale de la hanche (ATH) n'a pas été déterminée. La plupart des études qui ont comparé les différentes approches n'ont fait état que de données à court terme. Donc, la littérature nous renseigne peu sur leurs bienfaits à long terme. Le but de cette étude est de vérifier l'effet des 3 principales approches chirurgicales pour l'ATH sur les paramètres rapportés par les patients 5 ans après la chirurgie. Méthodes: Tous les patients soumis à une ATH pour arthrose ou ostéonécrose entre 2008 et 2012 par approche antérieure, postérieure ou latérale à l'Hôpital d'Ottawa, en Ontario, au Canada, ont été inclus dans l'étude; et tous les scores préopératoires et postopératoires des questionnaires HOOS (Hip Disability and Osteoarthritis Outcome Score) et WOMAC (Western Ontario and MacMaster Universities Osteoarthritis Index) ont été enregistrés. L'analyse de covariance a servi à étudier le lien entre l'ampleur des changements aux scores des sous-échelles HOOS et WOMAC (variables dépendantes) et l'approche chirurgicale. L'analyse a aussi tenu compte de facteurs de confusion tels que l'âge, le sexe, la classe ASA (American Society of Anesthesiologists), classification de Charnley et indice de masse corporell. Résultats: Le groupe soumis à l'approche postérieure comptait 138 patients (37,6 %), à l'approche latérale 104 (28,3 %) et à l'approche antérieure 125 (34,1 %). Il n'y avait pas de différences significatives entre les 3 groupes aux plans de la classification de Charnley, de l'indice de masse corporelle, du sexe, de la classe ASA, du côté où la chirurgie a été effectuée et des paramètres fonctionnels préopératoires. Nous n'avons observé aucune différence significative quant à l'ampleur du changement aux scores des sous-échelles HOOS et WOMAC entre les 3 groupes; il en est allé de même pour les scores postopératoires finaux. Conclusion: Selon nos observations, le choix de l'approche chirurgicale pour l'ATH primaire sans révision n'exerce aucune influence sur les paramètres fonctionnels et la qualité de vie après 5 ans. Il faudra procéder à d'autres études pour évaluer l'influence potentielle de l'âge et du sexe sur les paramètres fonctionnels des différentes approches.
Assuntos
Artroplastia de Quadril/métodos , Medidas de Resultados Relatados pelo Paciente , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , Osteoartrite do Quadril/cirurgia , Osteonecrose/cirurgia , Medição da Dor , Qualidade de Vida , Estudos RetrospectivosRESUMO
BACKGROUND: The success rate of surgical treatment for periprosthetic joint infection (PJI) remains inconsistent in the literature. Variability in PJI clinical guidelines and surgeon adherence to guidelines could affect treatment success. The objectives of this study were to appraise current recommendations for PJI management and develop a unified clinical standard of care, to perform a gap analysis of PJI cases in a tertiary institution to determine the rate of guideline adherence, and to determine if adherence to unified PJI guidelines affected 2-year treatment outcomes. METHODS: We appraised the PJI guidelines from 3 academic medical societies, and consistent statements were aggregated. We retrospectively reviewed all PJI cases in a tertiary care institution. We defined PJI based on Musculoskeletal Infection Society PJI criteria. Surgeon adherence to preoperative, intraoperative, surgical and medical management guidelines was calculated, and we evaluated the association between guideline adherence and 2-year treatment outcomes. RESULTS: The institutional rate of PJI was 1.13% (38 of 3368). Treatment success was 57.8% at 2 years. Unified guideline adherence percentages varied substantially: 92% of patients had preoperative erythrocyte sedimentation rate and C-reactive protein, 97% had intraoperative tissue cultures, 42% had appropriate preoperative arthrocentesis, and 74% underwent guideline-appropriate surgery. Performing appropriate preoperative arthrocentesis significantly correlated with positive treatment outcomes at 2 years (p = 0.028). CONCLUSION: Adherence to PJI guidelines varies considerably, indicating that clinicians are either unaware of them or do not recognize their value for PJI treatment. This study shows the need for institution-based PJI treatment pathways that are consistent with published guidelines and the need to monitor adherence.
CONTEXTE: Les études ne concordent pas quant au taux de réussite du traitement chirurgical des infections de prothèses articulaires (IPA). Une certaine variabilité dans les lignes directrices sur ces infections et dans l'adhésion des chirurgiens à celles-ci pourrait nuire à la réussite du traitement. La présente étude visait à évaluer les recommandations actuelles sur la prise en charge des IPA afin d'élaborer une norme de soins uniforme, à effectuer une analyse des lacunes entourant les cas d'IPA dans un établissement de soins tertiaires pour déterminer le taux d'adhésion aux lignes directrices, et à déterminer si l'adhésion à des lignes directrices uniformes influençait les issues de traitement après 2 ans. MÉTHODES: Nous avons évalué les lignes directrices sur les IPA de 3 sociétés médicales universitaires, et agrégé des énoncés cohérents. Nous avons également examiné de façon rétrospective tous les cas d'IPA dans un établissement de soins tertiaires. Aux fins de notre étude, l'IPA était définie selon les critères de la Musculoskeletal Infection Society. Nous avons calculé l'adhésion des chirurgiens aux lignes directrices de prise en charge préopératoire, peropératoire, chirurgicale et médicale, puis nous avons évalué l'association entre ce paramètre et les issues de traitement après 2 ans. RÉSULTATS: Le taux d'IPA dans l'établissement était de 1,13 % (38 sur 3368), et le taux de réussite du traitement était de 57,8 % après 2 ans. Les pourcentages d'adhésion aux lignes directrices variaient considérablement : 92 % des patients avaient eu une analyse préopératoire de la vitesse de sédimentation érythrocytaire et de la protéine C-réactive, 97 % avaient eu des cultures tissulaires peropératoires, 42 % avaient eu une arthrocentèse préopératoire appropriée, et 74 % avaient subi une intervention chirurgicale conforme aux lignes directrices. Il y avait une corrélation significative entre l'arthrocentèse préopératoire et les issues favorables après 2 ans (p = 0,028). CONCLUSION: L'adhésion aux lignes directrices sur les IPA varie considérablement, ce qui indique que les cliniciens ne les connaissent pas ou n'en reconnaissent pas la valeur pour le traitement des IPA. La présente étude montre qu'il faut dans les établissements des protocoles de traitement conformes aux lignes directrices publiées, et qu'il est nécessaire de surveiller l'adhésion des chirurgiens à celles-ci.
Assuntos
Artrite Infecciosa/epidemiologia , Artroplastia de Substituição/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Cuidados Intraoperatórios/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Assistência Perioperatória/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Infecções Relacionadas à Prótese/epidemiologia , Cirurgiões/estatística & dados numéricos , Centros de Atenção Terciária/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The poor prognosis of patients with advanced bone and soft-tissue sarcoma has not changed in the past several decades, highlighting the necessity for new therapeutic approaches. Immunotherapies, including oncolytic viral (OV) therapy, have shown great promise in a number of clinical trials for a variety of tumor types. However, the effective application of OV in treating sarcoma still remains to be demonstrated. Although few pre-clinical studies using distinct OVs have been performed and demonstrated therapeutic benefit in sarcoma models, a side-by-side comparison of clinically relevant OV platforms has not been performed. Four clinically relevant OV platforms (Reovirus, Vaccinia virus, Herpes-simplex virus and Rhabdovirus) were screened for their ability to infect and kill human and canine sarcoma cell lines in vitro, and human sarcoma specimens ex vivo. In vivo treatment efficacy was tested in a murine model. The rhabdovirus MG1 demonstrated the highest potency in vitro. Ex vivo, MG1 productively infected more than 80% of human sarcoma tissues tested, and treatment in vivo led to a significant increase in long-lasting cures in sarcoma-bearing mice. Importantly, MG1 treatment induced the generation of memory immune response that provided protection against a subsequent tumor challenge. This study opens the door for the use of MG1-based oncolytic immunotherapy strategies as treatment for sarcoma or as a component of a combined therapy.
Assuntos
Terapia Viral Oncolítica/métodos , Rhabdoviridae/fisiologia , Sarcoma/terapia , Sarcoma/virologia , Animais , Neoplasias Ósseas/terapia , Neoplasias Ósseas/virologia , Linhagem Celular Tumoral , Cães , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Osteossarcoma/terapia , Osteossarcoma/virologia , Sarcoma de Ewing/terapia , Sarcoma de Ewing/virologia , Sarcoma Sinovial/terapia , Sarcoma Sinovial/virologiaRESUMO
BACKGROUND: Greater trochanteric fracture/nonunion can be a devastating complication with significant functional impact after total hip arthroplasty, and their fixation remains a challenge because of the significant forces being transmitted as well as the poor bone quality often associated with these fractures. The objective of this study is to investigate the rates of reoperation and trochanteric nonunion using a third-generation cable-plate system at one center. METHODS: Thirty-five patients, mean age 72.9 years (range 46-98 years) with 24 women and 11 men, underwent fixation of their fractured greater trochanter using a third-generation cable-plate system. The indications were: periprosthetic fracture (n = 17), complex primary arthroplasty (n = 5), and complex revision arthroplasty (n = 13). Primary outcomes included rates of reoperation and radiographic union. RESULTS: At a mean follow-up of 2.5 years, trochanteric union rate was 62.9% with nonunion rate of 31.4%, and fibrous union in 5.7%. In regard to quality of initial apposition, only 40% achieved a perfect bone on bone reduction. Ten patients (28.6%) had evidence of wire breakage. Five patients (14.3%) required reoperation and removal of the internal fixation because of lateral hip pain. CONCLUSION: Fixation of the trochanteric fractures remains a challenge with a relatively high reoperation rate. Poor bone quality and capacity to maintain a stable reduction continue to make this complication after total hip arthroplasty a difficult problem to solve.
Assuntos
Artroplastia de Quadril/efeitos adversos , Fixação Interna de Fraturas , Fraturas não Consolidadas/cirurgia , Fraturas do Quadril/cirurgia , Reoperação/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Placas Ósseas/efeitos adversos , Fios Ortopédicos , Feminino , Fêmur/cirurgia , Fixação Interna de Fraturas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Dor , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The purpose of this study was to determine the incidence, and the clinical and radiographic risk factors for significant subsidence of a cementless, modular tapered revision femoral stem. Femoral stem subsidence of at least 10 mm or subsidence requiring revision was considered significant subsidence. Ninety-seven patients (99 hips) were included with minimum radiographic follow-up of one year (mean 34 months; range, 12-91 months). The mean stem subsidence was 4.5 mm (range, 0-44 mm). Fourteen out of 99 (14.1%) stems had significant subsidence and 6 (6.1%) stems required revision due to subsidence. Patient weight greater than 80 kg (P=0.04) and femoral stem press-fit distance of less than 2 cm (P<0.01) were both independent risk factors for significant stem subsidence.
Assuntos
Artroplastia de Quadril/efeitos adversos , Fêmur/cirurgia , Prótese de Quadril , Reoperação/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Fatores de RiscoRESUMO
UNLABELLED: Metastatic Ewing sarcoma (EWS) is often resistant to current multimodal chemotherapeutic regimens. Oncolytic virus therapy (OV) is a novel therapeutic platform whereby viruses can selectively infect as well as replicate in and kill tumor cells, while sparing normal tissues. The purpose of this study is to investigate the efficacy of the biotherapeutic oncolytic agent, vesicular stomatitis virus (VSVΔM51), to kill EWS cells that are resistant to conventional therapy. Our hypothesis is that systemic delivery of VSVΔM51 can demonstrate tumor-specific killing of resistant EWS cells, as well as a significant decrease of tumor burden in EWS bearing mice. METHODS: A biopsy sample was obtained from a patient with metastatic EWS and was used to establish a novel EWS cell line. In vitro assays evaluated the oncolytic effect of vesicular stomatitis virus (VSVΔM51) on this cell line. EWS xenograft mice model bearing either lung or subcutaneous tumors was established to evaluate the antitumor specific oncolytic effect of VSVΔM51 after local and systemic delivery. RESULTS: The established EWS cell line shared similar molecular and genetic traits to the patient's original tumor specimen. VSVΔM51 effectively infected and killed EWS cells in vitro. In vivo, VSVΔM51 selectively infected and killed EWS and led to significant delay in tumor growth. CONCLUSION: This study has been designed to implement a translational link between the bedside and the bench, where a specific challenging clinical scenario guided this basic science research. This research demonstrated that a sarcoma, which is resistant to current conventional standard therapies, is still susceptible to an alternative therapeutic platform, such as OV. Adding OV to the armamentarium of sarcoma treatment can enhance the future therapeutic approach towards these cancer patients.
Assuntos
Modelos Biológicos , Terapia Viral Oncolítica , Sarcoma de Ewing/terapia , Adulto , Animais , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Camundongos , Camundongos NusRESUMO
Background: Debridement, antibiotics, and implant retention (DAIR) is a well-accepted surgical strategy for periprosthetic joint infection (PJI) following total knee arthroplasty (TKA). DAIR in TKA may be incorrectly thought of as a "simple" procedure not requiring formal specialized training in arthroplasty. Currently, there are no studies comparing the risk of treatment failure based on surgeon fellowship training. Methods: A retrospective review was performed of consecutive patients who underwent DAIR for TKA PJI at our institution. Two cohorts were created based on whether DAIR was performed by an arthroplasty fellowship-trained (FT) surgeon or nonarthroplasty fellowship-trained (NoFT) surgeon. Primary outcome was treatment failure following DAIR at a minimum of 1 year postoperatively. Treatment failure was based on the Tier 1 International Consensus Meeting definition of infection control. Secondary outcomes were also recorded including death during the totality of PJI treatment. Results: A total of 112 patients were identified (FT = 68, NoFT = 44). At a mean follow-up of 7.3 years [standard deviation = 3.9], 73 patients (59.8%) failed treatment. Fellowship training in arthroplasty significantly improved treatment success rates (FT, 35/68 [51.5%]; NoFT, 10/44 [22.7%]; odds ratio 2.5 [95% confidence interval 1.1 to 5.9; P = .002]). Survivorship also differed significantly between the cohorts; at timepoints of 1.5 months, 5 months, 30 months, and 180 months, survivorship of the FT cohort was 79.4%, 67.6%, 54.4%, and 50.7%, respectively, compared with a survivorship of 65.9%, 52.3%, 25%, and 22.7% in the NoFT cohort (P = .002). Conclusions: TKA PJI treated with DAIR should not be considered a simple procedure. Improved treatment success may be associated with subspecialty fellowship training in arthroplasty. Level of Evidence: IV.
RESUMO
There is controversial clinical evidence regarding the added antibacterial benefit of locally administering antiseptic solutions or antibiotics to the infected joint space. The objectives of this in vitro study were to test the efficacy of povidone-iodine (PVP-I) and vancomycin in treating premature and developed Staphylococcus aureus biofilms grown on titanium implant surfaces. PVP-I and vancomycin were used to treat immature and developed biofilms formed by two clinical strains of S. aureus (BP043-MRSA, PB011-MSSA). S. aureus strains were grown as immature (3 h-old) or developed (24 h-old) biofilm. These biofilms were grown on titanium plasma sprayed discs. The treatment regimens tested were: 0.8% PVP-I, 500 µg/ml vancomycin as well as a combination of vancomycin and PVP-I. PVP-I was tested at 3 min, as per current clinical practice, versus 1 min treatment times. In addition, the cytotoxicity of the PVP-I and vancomycin was tested using fresh skeletal muscle tissue cores harvested from the rat's abdominal muscles using alamarBlue assay. The combination of PVP-I (3 min) and vancomycin (24 h.) showed synergistic interaction and the best efficacy against immature biofilms formed by both clinical strains. This degree of eradication was statistically significant compared to the untreated control, p < .0001. However, this combination therapy had limited efficiency against developed biofilms. Also, PVP-I alone was more effective when exposure time was 3 min instead of 1 min against immature biofilm for MRSA, p = .02, and MSSA, p = .01. PVP-I and vancomycin were not effective against developed biofilm regardless of exposure time. Also, combining PVP-I and vancomycin was not cytotoxic to muscle tissue. Combining PVP-I with vancomycin is superior in reducing viable S. aureus cells in immature biofilms grown on titanium surface without causing significant cytotoxicity to muscle tissue. Exposure times and biofilm maturity play a role in dictating the efficacy of using local antiseptics and antibiotics to treat biofilms on implant surfaces.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Animais , Ratos , Vancomicina/farmacologia , Povidona-Iodo/farmacologia , Staphylococcus aureus , Meticilina , Titânio/farmacologia , Antibacterianos/farmacologia , Biofilmes , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Gram-negative periprosthetic joint infections (GN-PJIs) present unique challenges. Our aim was to establish a clinically representative GN-PJI model that recapitulates biofilm formation in vivo. We also hypothesized that biofilm formation on the implant surface would affect its ability to osseointegrate. METHODS: Three-dimensionally-printed medical-grade titanium hip implants were used to replace the femoral heads of male Sprague-Dawley rats. GN-PJI was induced using 2 bioluminescent Pseudomonas aeruginosa strains: a reference strain (PA14-lux) and a mutant biofilm-defective strain (ΔflgK-lux). Infection was monitored in real time using an in vivo imaging system (IVIS) and magnetic resonance imaging (MRI). Bacterial loads were quantified utilizing the viable colony count. Biofilm formation at the bone-implant interface was visualized using field-emission scanning electron microscopy (FE-SEM). Implant stability, as an outcome, was directly assessed by quantifying osseointegration using microcomputed tomography, and indirectly assessed by identifying gait-pattern changes. RESULTS: Bioluminescence detected by the IVIS was focused on the hip region and demonstrated localized infection, with greater ability of PA14-lux to persist in the model compared with the ΔflgK-lux strain, which is defective in biofilm formation. This was corroborated by MRI, as PA14-lux induced relatively larger implant-related abscesses. Biofilm formation at the bone-implant interface induced by PA14-lux was visualized using FE-SEM versus defective-biofilm formation by ΔflgK-lux. Quantitatively, the average viable colony count of the sonicated implants, in colony-forming units/mL, was 3.77 × 108 for PA14-lux versus 3.65 × 103 for ΔflgK-lux, with a 95% confidence interval around the difference of 1.45 × 108 to 6.08 × 108 (p = 0.0025). This difference in the ability to persist in the model was reflected significantly on implant osseointegration, with a mean intersection surface of 4.1 × 106 ± 1.99 × 106 µm2 for PA14-lux versus 6.44 × 106 ± 2.53 × 106 µm2 for ΔflgK-lux and 7.08 × 106 ± 1.55 × 106 µm2 for the noninfected control (p = 0.048). CONCLUSIONS: To our knowledge, this proposed, novel in vivo biofilm-based model is the most clinically representative for GN-PJI to date, since animals can bear weight on the implant, poor osseointegration was associated with biofilm formation, and localized PJI was assessed by various modalities. CLINICAL RELEVANCE: This model will allow for more reliable testing of novel biofilm-targeting therapeutics.
Assuntos
Artrite Infecciosa , Hemiartroplastia , Prótese de Quadril , Infecções Relacionadas à Prótese , Ratos , Masculino , Animais , Infecções Relacionadas à Prótese/microbiologia , Microtomografia por Raio-X , Ratos Sprague-Dawley , Biofilmes , Prótese de Quadril/efeitos adversos , Artrite Infecciosa/tratamento farmacológico , Antibacterianos/uso terapêuticoRESUMO
Periprosthetic joint infection (PJI) following total hip and total knee arthroplasty continues to be a leading cause of re-operation and revision arthroplasty. Not only is the treatment of PJI notoriously challenging, but success rates are variable. Regardless of the surgical strategy used, successful management of PJI requires a comprehensive surgical debridement focused at eradicating the underlying biofilm followed by appropriate antimicrobial therapy. Although systemic antimicrobial delivery continues to be a cornerstone in the treatment of PJI, many surgeons have started using local antibiotics to deliver higher concentrations of antibiotics directly into the vulnerable joint and adjacent soft tissues, which often have compromised vascularity. Available evidence on the use of topical powder, bone cement, and calcium sulphate carriers for local delivery of antibiotics during the initial treatment of PJI is limited to studies that are extremely heterogeneous. There is currently no level-1 evidence to support routinely using these products. Further, appropriately powered, prospective studies are needed to quantify the safety and efficacy of antibiotic-located calcium-sulphate carriers to justify their added costs. These products should not encourage surgeons to deviate from best practice guidelines, such as those recommended during the International Consensus Meeting on Musculoskeletal Infections.
Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Infecções Relacionadas à Prótese , Humanos , Antibacterianos/uso terapêutico , Artroplastia de Quadril/efeitos adversos , Infecções Relacionadas à Prótese/cirurgia , Artroplastia do Joelho/efeitos adversos , Cimentos Ósseos/uso terapêutico , Estudos RetrospectivosRESUMO
Background: Biofilm formation is a major clinical challenge contributing to treatment failure of periprosthetic joint infection (PJI). Lytic bacteriophages (phages) can target biofilm associated bacteria at localized sites of infection. The aim of this study is to investigate whether combination therapy of phage and vancomycin is capable of clearing Staphylococcus aureus biofilm-like aggregates formed in human synovial fluid. Methods: In this study, S. aureus BP043, a PJI clinical isolate was utilized. This strain is a methicillin-resistant S. aureus (MRSA) biofilm-former. Phage Remus, known to infect S. aureus, was selected for the treatment protocol. BP043 was grown as aggregates in human synovial fluid. The characterization of S. aureus aggregates was assessed for structure and size using scanning electron microscopy (SEM) and flow cytometry, respectively. Moreover, the formed aggregates were subsequently treated in vitro with: (a) phage Remus [â¼108 plaque-forming units (PFU)/ml], (b) vancomycin (500 µg/ml), or (c) phage Remus (â¼108 PFU/ml) followed by vancomycin (500 µg/ml), for 48 h. Bacterial survival was quantified by enumeration [colony-forming units (CFU)/ml]. The efficacy of phage and vancomycin against BP043 aggregates was assessed in vivo as individual treatments and in combination. The in vivo model utilized Galleria mellonella larvae which were infected with BP043 aggregates pre-formed in synovial fluid. Results: Scanning electron microscopy (SEM) images and flow cytometry data demonstrated the ability of human synovial fluid to promote formation of S. aureus aggregates. Treatment with Remus resulted in significant reduction in viable S. aureus residing within the synovial fluid aggregates compared to the aggregates that did not receive Remus (p < 0.0001). Remus was more efficient in eliminating viable bacteria within the aggregates compared to vancomycin (p < 0.0001). Combination treatment of Remus followed by vancomycin was more efficacious in reducing bacterial load compared to using either Remus or vancomycin alone (p = 0.0023, p < 0.0001, respectively). When tested in vivo, this combination treatment also resulted in the highest survival rate (37%) 96 h post-treatment, compared to untreated larvae (3%; p < 0.0001). Conclusion: We demonstrate that combining phage Remus and vancomycin led to synergistic interaction against MRSA biofilm-like aggregates in vitro and in vivo.
RESUMO
The increase in outbreaks of emerging and re-emerging bacterial infections over the last few decades calls for their rapid detection and treatment. Surface-enhanced Raman spectroscopy (SERS) is a technique that can be applied to develop fast screening systems for bacterial presence in biological samples. Optimizing the capping agents in nanoparticle synthesis is important because capping agents are responsible for controlling the morphological features and chemical properties of the nanoparticles that are essential for SERS. To the best of our knowledge, this paper is the first to study the application of gold nanoparticles capped with thioglucose and polyvinylpyrrolidone (PVP) in SERS detection of bacteria as an alternative to the citrate-capped gold nanoparticles that are often used in SERS detection of bacteria. Three different species of bacteria were used in this study: Cutibacterium acnes, Escherichia coli and Staphylococcus aureus (methicillin-sensitive and methicillin-resistant). This study demonstrates that the thioglucose, citrate both show good contribution in bacterial species identification and the thioglucose shows the best among the three capping agents in two types of S. aureus identification. Moreover, although PVP showed high Raman peaks in the SERS spectrum for each type of bacteria, it showed least contribution in identifying species and strains due to its low efficacy in producing responses from different nucleic acid components in the bacteria cells.
Assuntos
Ouro , Nanopartículas Metálicas , Bactérias , Citratos , Ácido Cítrico , Escherichia coli , Ouro/química , Nanopartículas Metálicas/química , Povidona , Análise Espectral Raman/métodos , Staphylococcus aureusRESUMO
Functional reconstruction of the upper extremity has traditionally involved tendon transfer or pedicled muscle transfer. The gracilis free functional muscle transfer remains as an excellent option for restoration of finger flexion. Here, we provide a case report of a 35-year-old man diagnosed with left forearm high-grade epithelioid sarcoma who underwent innervated free gracilis transfer and a secondary free flap, the profunda artery perforator flap, through a single donor-site incision to expand soft tissue coverage. Postoperatively, there were no complications reported. At 8-month follow-up, the patient had Musculoskeletal Tumor Score of 22/30, and a Quick Disabilities of the Arm, Shoulder, and Hand score of 34/100.
RESUMO
AIMS: The aims of this study were to determine the incidence and factors for developing periprosthetic joint infection (PJI) following hemiarthroplasty (HA) for hip fracture, and to evaluate treatment outcome and identify factors associated with treatment outcome. METHODS: A retrospective review was performed of consecutive patients treated for HA PJI at a tertiary referral centre with a mean 4.5 years' follow-up (1.6 weeks to 12.9 years). Surgeries performed included debridement, antibiotics, and implant retention (DAIR) and single-stage revision. The effect of different factors on developing infection and treatment outcome was determined. RESULTS: A total of 1,984 HAs were performed during the study period, and 44 sustained a PJI (2.2%). Multiple logistic regression analysis revealed that a higher CCI score (odds ratio (OR) 1.56 (95% confidence interval (CI) 1.117 to 2.187); p = 0.003), peripheral vascular disease (OR 11.34 (95% CI 1.897 to 67.810); p = 0.008), cerebrovascular disease (OR 65.32 (95% CI 22.783 to 187.278); p < 0.001), diabetes (OR 4.82 (95% CI 1.903 to 12.218); p < 0.001), moderate-to-severe renal disease (OR 5.84 (95% CI 1.116 to 30.589); p = 0.037), cancer without metastasis (OR 6.42 (95% CI 1.643 to 25.006); p = 0.007), and metastatic solid tumour (OR 15.64 (95% CI 1.499 to 163.087); p = 0.022) were associated with increasing PJI risk. Upon final follow-up, 17 patients (38.6%) failed initial treatment and required further surgery for HA PJI. One-year mortality was 22.7%. Factors associated with treatment outcome included lower preoperative Hgb level (97.9 g/l (SD 11.4) vs 107.0 g/l (SD 16.1); p = 0.009), elevated CRP level (99.1 mg/l (SD 63.4) vs 56.6 mg/l (SD 47.1); p = 0.030), and type of surgery. There was lower chance of success with DAIR (42.3%) compared to revision HA (66.7%) or revision with conversion to total hip arthroplasty (100%). Early-onset PJI (≤ six weeks) was associated with a higher likelihood of treatment failure (OR 3.5 (95% CI 1.2 to 10.6); p = 0.007) along with patients treated by a non-arthroplasty surgeon (OR 2.5 (95% CI 1.2 to 5.3); p = 0.014). CONCLUSION: HA PJI initially treated with DAIR is associated with poor chances of success and its value is limited. We strongly recommend consideration of a single-stage revision arthroplasty with cemented components.Cite this article: Bone Jt Open 2022;3(12):924-932.
RESUMO
â¢: Periprosthetic joint infection (PJI) following hip hemiarthroplasty (HA) is a devastating complication, incurring immense health-care costs associated with its treatment and placing considerable burden on patients and their families. These patients often require multiple surgical procedures, extended hospitalization, and prolonged antimicrobial therapy. â¢: Notable risk factors include older age, higher American Society of Anesthesiologists (ASA) score, inadequate antibiotic prophylaxis, non-antibiotic-loaded cementation of the femoral implant, longer duration of the surgical procedure, and postoperative drainage and hematoma. â¢: Although the most frequent infecting organisms are gram-positive cocci such as Staphylococcus aureus, there is a higher proportion of patients with gram-negative and polymicrobial infections after hip HA compared with patients who underwent total hip arthroplasty. â¢: Several surgical strategies exist. Regardless of the preferred surgical treatment, successful management of these infections requires a comprehensive surgical debridement focused on eradicating the biofilm followed by appropriate antibiotic therapy. â¢: A multidisciplinary approach led by surgeons familiar with PJI treatment and infectious disease specialists is recommended for all cases of PJI after hip HA to increase the likelihood of treatment success.
Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Hemiartroplastia , Infecções Relacionadas à Prótese , Antibacterianos/uso terapêutico , Artrite Infecciosa/etiologia , Artroplastia de Quadril/efeitos adversos , Hemiartroplastia/efeitos adversos , Humanos , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/terapiaRESUMO
Oncolytic viruses (OVs) are promising anticancer agents but like other cancer monotherapies, the genetic heterogeneity of human malignancies can lead to treatment resistance. We used a virus/cell-based assay to screen diverse chemical libraries to identify small molecules that could act in synergy with OVs to destroy tumor cells that resist viral infection. Several molecules were identified that aid in viral oncolysis, enhancing virus replication and spread as much as 1,000-fold in tumor cells. One of these molecules we named virus-sensitizers 1 (VSe1), was found to target tumor innate immune response and could enhance OV efficacy in animal tumor models and within primary human tumor explants while remaining benign to normal tissues. We believe this is the first example of a virus/cell-based "pharmacoviral" screen aimed to identify small molecules that modulate cellular response to virus infection and enhance oncolytic virotherapy.
Assuntos
Terapia Viral Oncolítica , Animais , Linhagem Celular Tumoral , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/terapiaRESUMO
Intratumoral innate immunity can play a significant role in blocking the effective therapeutic spread of a number of oncolytic viruses (OVs). Histone deacetylase inhibitors (HDIs) are known to influence epigenetic modifications of chromatin and can blunt the cellular antiviral response. We reasoned that pretreatment of tumors with HDIs could enhance the replication and spread of OVs within malignancies. Here, we show that HDIs markedly enhance the spread of vesicular stomatitis virus (VSV) in a variety of cancer cells in vitro, in primary tumor tissue explants and in multiple animal models. This increased oncolytic activity correlated with a dampening of cellular IFN responses and augmentation of virus-induced apoptosis. These results illustrate the general utility of HDIs as chemical switches to regulate cellular innate antiviral responses and to provide controlled growth of therapeutic viruses within malignancies. HDIs could have a profoundly positive impact on the clinical implementation of OV therapeutics.
Assuntos
Inibidores Enzimáticos/uso terapêutico , Inibidores de Histona Desacetilases , Neoplasias/terapia , Terapia Viral Oncolítica , Vírus Oncolíticos/efeitos dos fármacos , Animais , Benzamidas/uso terapêutico , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Imunidade Inata/efeitos dos fármacos , Interferons/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos , Neoplasias/tratamento farmacológico , Neoplasias/virologia , Vírus Oncolíticos/imunologia , Vírus Oncolíticos/fisiologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/terapia , Neoplasias da Próstata/virologia , Piridinas/uso terapêutico , Vesiculovirus/efeitos dos fármacos , Vesiculovirus/imunologia , Vesiculovirus/fisiologia , Replicação Viral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
AIMS: The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time. METHODS: Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces. RESULTS: All animals tolerated surgery well, with preservation of gait mechanics and weightbearing in control individuals. Postoperative in vivo imaging demonstrated predictable evolution of infection with logarithmic signal decay coinciding with abscess formation. Postmortem mCT qualitative volumetric analysis showed high contact area and both cement-bone and cement-implant interdigitation. FE-SEM revealed biofilm formation on the prosthetic head. CONCLUSION: This study demonstrates the utility of a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Inoculation with bioluminescent bacteria allows for non-invasive, real-time monitoring of infection. Cite this article: Bone Joint J 2021;103-B(7 Supple B):9-16.
Assuntos
Hemiartroplastia , Prótese de Quadril , Infecções Relacionadas à Prótese/diagnóstico por imagem , Infecções Relacionadas à Prótese/microbiologia , Infecções Estafilocócicas/diagnóstico por imagem , Infecções Estafilocócicas/microbiologia , Animais , Distinções e Prêmios , Biofilmes , Cimentos Ósseos , Modelos Animais de Doenças , Marcha , Masculino , Microscopia Eletrônica de Varredura , Impressão Tridimensional , Ratos , Ratos Sprague-Dawley , Microtomografia por Raio-XRESUMO
BACKGROUND: Our objective was to identify combination tests used to diagnose chronic periprosthetic joint infection (PJI) and develop a stepwise decision-making tool to facilitate diagnosis. METHODS: We conducted a systematic review of existing combinations of serum, synovial, and tissue-based tests for diagnosing chronic PJI after hip or knee replacement. This work is an extension of our systematic review of single tests, from which we chose eligible studies that also described the diagnostic performance of combination tests. RESULTS: Thirty-seven eligible articles described the performance of 56 combination tests, of which 8 combinations had at least 2 studies informing both sensitivity and specificity. We also identified 5 types of combination tests: (1) a type-I Boolean combination, which uses Boolean logic (AND, OR) and usually increases specificity at the cost of sensitivity; (2) a type-II Boolean combination, which usually increases sensitivity at the cost of specificity; (3) a triage-conditional rule, in which the value of 1 test serves to triage the use of another test; (4) an arithmetic operation on the values of 2 tests; and (5) a model-based prediction rule based on a fitted model applied to biomarker values. CONCLUSIONS: Clinicians can initiate their diagnostic process with a type-II Boolean combination of serum C-reactive protein (CRP) and interleukin-6 (IL-6). False negatives of the combination can be minimized when the threshold is chosen to reach 90% to 95% sensitivity for each test. Once a joint infection is suspected on the basis of serum testing, joint aspiration should be performed. If joint aspiration yields a wet tap, a leukocyte esterase (LER) strip is highly recommended for point-of-care testing, with a reading of ++ or greater indicating PJI; a reading below ++ should be followed by one of the laboratory-based synovial tests. If joint aspiration yields a dry tap, clinicians should rely on preoperative tissue culture and histological analysis for diagnosis. Combinations based on triage-conditional, arithmetic, and model-based prediction rules require further research. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.