Enhancing the data capture of periprosthetic joint infections in the Danish Knee Arthroplasty Registry: validity assessment and incidence estimation.

BACKGROUND AND PURPOSE: Revisions due to periprosthetic joint infection (PJI) are underestimated in national arthroplasty registries. Our primary objective was to assess the validity in the Danish Knee Arthroplasty Register (DKR) of revisions performed due to PJI against the Healthcare-Associated Infections Database (HAIBA). The secondary aim was to describe the cumulative incidences of revision due to PJI within 1 year of primary total knee arthroplasty (TKA) according to the DKR, HAIBA, and DKR/HAIBA combined. METHODS: This longitudinal observational cohort study included 56,305 primary TKAs (2010-2018), reported in both the DKR and HAIBA. In the DKR, revision performed due to PJI was based on pre- and intraoperative assessment disclosed by the surgeon immediately after surgery. In HAIBA, PJI was identified from knee-related revision procedures coinciding with 2 biopsies with identical microbiological pathogens. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of revision due to PJI in the DKR (vs. HAIBA, within 1 year of TKA) with 95% confidence intervals (CI). Cumulative incidences were calculated using the Kaplan-Meier method. RESULTS: The DKR's sensitivity for PJI revision was 58% (CI 53-62) and varied by TKA year (41%-68%) and prosthetic type (31% for monoblock; 63% for modular). The specificity was 99.8% (CI 99.7-99.8), PPV 64% (CI 62-72), and NPV 99.6% (CI 99.6-99.7). 80% of PJI cases not captured by the DKR were caused by non-reporting rather than misclassification. 33% of PJI cases in the DKR or HAIBA were culture-negative. Considering potential misclassifications, the best-case sensitivity was 64%. The cumulative incidences of PJI were 0.8% in the DKR, 0.9% in HAIBA, and 1.1% when combining data. CONCLUSION: The sensitivity of revision due to PJI in the DKR was 58%. The cumulative incidence of PJI within 1 year after TKA was highest (1.1%) when combining the DKR and HAIBA, showing that incorporating microbiology data into arthroplasty registries can enhance PJI validity.

Current Concepts on the Clinical and Economic Impact of Periprosthetic Joint Infections.

Total joint arthroplasty (TJA) is a common procedure performed throughout the entire world in hopes of alleviating debilitating hip or knee pain. The projected number of TJAs performed in the United States alone is projected to exceed 1.9 million by 2030 and 5 million by 2040. With the significant increase in TJA performed, more periprosthetic joint infections (PJIs) are likely to be encountered. PJIs are a devastating complication of TJA. The economic and clinical burden must be understood and respected to minimize occurrence and allow optimal patient outcomes.

The BLISTER Score: A Novel, Externally Validated Tool for Predicting Cardiac Implantable Electronic Device Infections, and Its Cost-Utility Implications for Antimicrobial Envelope Use.

BACKGROUND: Antimicrobial envelopes reduce the incidence of cardiac implantable electronic device infections, but their cost restricts routine use in the United Kingdom. Risk scoring could help to identify which patients would most benefit from this technology. METHODS: A novel risk score (BLISTER [Blood results, Long procedure time, Immunosuppressed, Sixty years old (or younger), Type of procedure, Early re-intervention, Repeat procedure]) was derived from multivariate analysis of factors associated with cardiac implantable electronic device infection. Diagnostic utility was assessed against the existing PADIT score (Prior procedure, Age, Depressed renal function, Immunocompromised, Type of procedure) in both standard and high-risk external validation cohorts, and cost-utility models examined different BLISTER and PADIT score thresholds for TYRX (Medtronic; Minneapolis, MN) antimicrobial envelope allocation. RESULTS: In a derivation cohort (n=7383), cardiac implantable electronic device infection occurred in 59 individuals within 12 months of a procedure (event rate, 0.8%). In addition to the PADIT score constituents, lead extraction (hazard ratio, 3.3 [95% CI, 1.9-6.1]; P<0.0001), C-reactive protein >50 mg/L (hazard ratio, 3.0 [95% CI, 1.4-6.4]; P=0.005), reintervention within 2 years (hazard ratio, 10.1 [95% CI, 5.6-17.9]; P<0.0001), and top-quartile procedure duration (hazard ratio, 2.6 [95% CI, 1.6-4.1]; P=0.001) were independent predictors of infection. The BLISTER score demonstrated superior discriminative performance versus PADIT in the standard risk (n=2854, event rate: 0.8%, area under the curve, 0.82 versus 0.71; P=0.001) and high-risk validation cohorts (n=1961, event rate: 2.0%, area under the curve, 0.77 versus 0.69; P=0.001), and in all patients (n=12 198, event rate: 1%, area under the curve, 0.8 versus 0.75, P=0.002). In decision-analytic modeling, the optimum scenario assigned antimicrobial envelopes to patients with BLISTER scores ≥6 (10.8%), delivering a significant reduction in infections (relative risk reduction, 30%; P=0.036) within the National Institute for Health and Care Excellence cost-utility thresholds (incremental cost-effectiveness ratio, £18 446). CONCLUSIONS: The BLISTER score (https://qxmd.com/calculate/calculator_876/the-blister-score-for-cied-infection) was a valid predictor of cardiac implantable electronic device infection, and could facilitate cost-effective antimicrobial envelope allocation to high-risk patients.

How good are surgeons at disclosing periprosthetic joint infection at the time of revision, based on pre- and intra-operative assessment? A study on 16,922 primary total hip arthroplasties reported to the Norwegian Arthroplasty Register.

BACKGROUND AND PURPOSE: Revision due to infection, as reported to the Norwegian Arthroplasty Register (NAR), is a surrogate endpoint to periprosthetic joint infection (PJI). We aimed to find the accuracy of the reported causes of revision after primary total hip arthroplasty (THA) compared with PJI to see how good surgeons were at disclosing infection, based on pre- and intraoperative assessment. PATIENTS AND METHODS: We investigated the reasons for revision potentially caused by PJI following primary THA: infection, aseptic loosening, prolonged wound drainage, and pain only, reported to the NAR from surgeons in the region of Western Norway during the period 2010-2020. The electronic patient charts were investigated for information on clinical assessment, treatment, biochemistry, and microbiological findings. PJI was defined in accordance with the Musculoskeletal Infection Society (MSIS) definition. Sensitivity, specificity, and accuracy were calculated. RESULTS: 363 revisions in the NAR were eligible for analyses. Causes of revision were (reported/validated): infection (153/177), aseptic loosening (139/133), prolonged wound drainage (37/13), and pain only (34/40). The sensitivity for reported revision due to infection compared with PJI was 80%, specificity was 94%, and accuracy-the surgeons' ability to disclose PJI or non-septic revision at time of revision-was 87%. The accuracy for the specific revision causes was highest for revision due to aseptic loosening (95%) and pain only (95%), and lowest for revision due to prolonged wound drainage (86%). CONCLUSION: The accuracy of surgeon-reported revisions due to infection as representing PJI was 87% in the NAR. Our study shows the importance of systematic correction of the reported cause of revision in arthroplasty registers, after results from adequately taken bacterial samples.

Neutrophil to Lymphocyte Ratio as an Indicator of Periprosthetic Joint Infection: A Retrospective Cohort Study.

INTRODUCTION: Periprosthetic joint infection (PJI) after total joint arthroplasty (TJA) is a serious complication posing notable clinical implications for patients and substantial economic burdens. Neutrophil to lymphocyte ratio (NLR) is an emerging biomarker of inflammation, which may better predict PJI. The objective of this review was to evaluate NLR changes in patients with confirmed PJI, to compare NLR between an aseptic revision and a revision for PJI, and to establish whether an NLR of 2.45 is an appropriate cutoff for predicting infection. METHODS: A retrospective review of patients who underwent revision TJA for PJI at a single center between January 1, 2005, and December 31, 2018, was performed and compared with an aseptic cohort who underwent aseptic revision TJA. NLR was calculated from complete blood counts performed at index surgery and at the time of revision surgery. Receiver operating characteristic curves were analyzed, along with sensitivity, specificity, and positive and negative likelihood ratios. RESULTS: There were 89 patients included in each cohort. Mean NLR in patients who underwent revision for PJI was 2.85 (± 1.27) at the time of index surgery and 6.89 (± 6.64) at the time of revision surgery ( P = 0.017). Mean NLR in patients undergoing revision for PJI (6.89) was significantly higher than aseptic revisions (3.17; P < 0.001). DISCUSSION: In patients who underwent revision surgery for PJI, NLR was markedly elevated at time of revision compared with the time of index surgery. Because it is a cost-effective and readily available test, these findings suggest that NLR may be a useful triage test in the diagnosis of PJI. LEVEL OF EVIDENCE: Level III Diagnostic Study.

Prevalence, interpretation, and management of unexpected positive cultures in revision TKA: a systematic review.

PURPOSE: Unexpected positive intraoperative cultures (UPIC) found in revision total knee arthroplasty (TKA) are difficult to interpret. Management goes along with risks for both over- and undertreating a potential periprosthetic joint infection (PJI). The objective of this systematic review was to determine the prevalence of UPIC in revision TKA surgery, evaluate the diagnostic workup process and the postoperative treatment, and assess outcome regarding re-revision rates. METHODS: Evidence was gathered from Medline (PubMed) and Embase published from January 2000 until April 2021. Nine studies with data of UPIC in revision TKA and outcome after at least 2 years of follow-up were identified. RESULTS: The calculated prevalence of UPIC in aseptic knee revision surgery was 8.32%. However, the diagnostical approach differs as well as the used criteria to confirm PJI in presumed aseptic revision surgery. The work-up generally consists of a serum C-reactive protein and Erythrocyte Sedimentation Rate, joint fluid aspiration for culture and white blood cell count and formula, and radiographic imaging. Collection of intraoperative cultures is widely used, but inconsistent in sample amount and incubation time. Once a single UPIC is found, surgeons tend to treat it in different ways. Regarding re-revision rates, the weighted arithmetic mean in the included studies was 18.45% in the unsuspected PJI group compared to 2.94% in the aseptic group. There also seems to be a trend towards higher re-revision rates when a higher number of intraoperative cultures are positive. CONCLUSION: The interpretation of UPIC in revision TKA is of utmost importance since the decision whether to treat a UPIC as an unsuspected PJI has a major impact on implant survival and re-revision rate. Different criteria are used to differentiate between unsuspected PJI and contamination in true aseptic failure, and the heterogeneity amongst the included papers impedes to state a clear recommendation, integrating not only quantitative findings, but also qualitative data such as virulence of the identified microorganism. LEVEL OF EVIDENCE: Systematic review, III.

Infections associated with cardiac electronic implantable devices: economic perspectives and impact of the TYRX™ antibacterial envelope.

The occurrence of cardiac implantable electronic devices (CIED) infections and related adverse outcomes have an important financial impact on the healthcare system, with hospitalization length of stay (2-3 weeks on average) being the largest cost driver, including the cost of device system extraction and device replacement accounting for more than half of total costs. In the recent literature, the economic profile of the TYRX™ absorbable antibacterial envelope was analysed taking into account both randomized and non-randomized trial data. Economic analysis found that the envelope is associated with cost-effectiveness ratios below USA and European benchmarks in selected patients at increased risk of infection. Therefore, the TYRX™ envelope, by effectively reducing CIED infections, provides value according to the criteria of affordability currently adopted by USA and European healthcare systems.

Accuracy and Cost-Effectivenss of a Novel Method for Alpha Defensins Measurement in the Diagnosis of Periprosthetic Joint Infections.

BACKGROUND: Two methods for detecting synovial fluids alpha defensins are available: the enzyme-linked immunosorbent assay and the lateral flow test. For both, the proper role and accuracy remain uncertain. The purpose of this study was to assess the accuracy of the matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) for alpha defensin detection in synovial fluids of patients with total knee arthroplasty/total hip arthroplasty failures. The hypothesis was that the alpha defensin measurement through MALDI-TOF MS assay could be a high sensitive and specific test for periprosthetic joint infections (PJI) diagnosis as compared with Musculoskeletal Infection Society (MSIS) criteria. METHODS: The study included 138 patients. The 2018 MSIS criteria were used to diagnose PJIs. Synovial fluids were assessed for routinely synovial fluid tests and alpha defensin measurement through MALDI-TOF MS. Sensitivity, specificity, overall diagnostic accuracy, positive and negative predictive values, receiver operator curves, and area under the curve were calculated. RESULTS: As per the 2018 MSIS criteria, 59 PJIs (43%) and 79 aseptic failures (57%) were diagnosed. The MALDI-TOF MS assay showed an overall accuracy of 94.9%. The sensitivity was 93%, the specificity was 96%, the positive predictive value was 95%, and the negative predictive value was 95%. Receiver operator curves analysis demonstrates an area under the curve of 0.95 (P < .001). CONCLUSION: The MALDI-TOF MS assay showed high sensitivity and specificity for alpha defensin detection in case of total knee arthroplasty/total hip arthroplasty failures. The advantages of the technology, such as the few milliliters of sample needed, the rapidity of obtaining results, and the cost-effectiveness of the procedure could make the MALDI-TOF MS alpha defensin assay a useful and widespread test in clinical practice.

The utility and cost of atypical cultures in revision shoulder arthroplasty.

BACKGROUND: At the time of revision shoulder arthroplasty, it is common practice to take cultures to evaluate for prosthetic joint infection even when an alternative cause of failure has been identified. Although isolation of fungal or acid-fast organisms is rare, it remains common practice to send all specimens for aerobic, anaerobic, and atypical (fungal and acid-fast) cultures. We hypothesize that the rate of positive atypical cultures at the time of revision shoulder arthroplasty is very low and routine use imposes a considerable financial burden on the health care system. METHODS: A retrospective review of all revision shoulder arthroplasties performed between January 1, 2010, and December 31, 2019, at our institution was performed. Patients with a hemiarthroplasty, total shoulder arthroplasty, reverse shoulder arthroplasty, or pre-existing antibiotic spacer who underwent revision to hemiarthroplasty, total shoulder arthroplasty, reverse shoulder arthroplasty, antibiotic spacer, or resection arthroplasty were included. Electronic patient charts were reviewed to gather patient, surgical, and culture data. An analysis of the hospital billing charges associated with each culture was performed using our hospital billing database and the current procedural terminology (CPT) codes for aerobic, anaerobic, fungal, and acid-fast cultures. A secondary outcome analysis was performed to identify factors associated with positive cultures. RESULTS: A total of 237 revision shoulder arthroplasties performed on 189 patients were analyzed. Cultures were sent on 158 of 237 (66.7%) surgeries with an average of 2.2 specimens per surgery. A total of 341 aerobic, 331 anaerobic, 187 fungal, and 174 acid-fast cultures were collected. Positive cultures were found in 52 of 341 (15.2%) aerobic cultures and 36 of 331 (10.9%) anaerobic cultures. The most commonly isolated organism was Cutibacterium acnes (42.2%), followed by methicillin-resistant Staphylococcus aureus (15.6%), coagulase-negative Staphylococcus species (13.3%), and methicillin-sensitive S. aureus (12.2%). There were zero positive fungal or acid-fast cultures in our series. The total billing charges for aerobic, anaerobic, fungal, and acid-fast cultures over the study period were $77,748, $23,832, $8,789, and $106,662, respectively, with atypical cultures accounting for 53.2% of the total charges for all cultures. For a single sample sent for all 4 culture types, atypical cultures account for 69% of the total amount charged. CONCLUSION: Isolation of fungal or acid-fast organisms at the time of revision shoulder arthroplasty is rare and imposes a considerable financial burden when these atypical cultures are sent on a routine basis. The collection of fungal and acid-fast cultures should be reserved for patients in whom risk factors for these atypical organisms have been identified.

Economic evaluation of an absorbable antibiotic envelope for prevention of cardiac implantable electronic device infection.

AIMS: Recent evidence suggests that an antibiotic impregnated envelope inserted at time of cardiac implantable electronic device (CIED) implantation may reduce risk of subsequent CIED infection compared with standard of care (SoC). The objective of the current work was to perform a cost-effectiveness analysis comparing an antibiotic impregnated envelope with SoC at time of CIED insertion. METHODS AND RESULTS: Decision analytic models were used to project healthcare costs and benefits of two strategies, an antibiotic impregnated envelope plus SoC (Env+SoC) vs. SoC alone, in a cohort of patients undergoing CIED implantation over a 1-year time horizon. Evidence from published literature informed the model inputs. Probabilistic and deterministic sensitivity analyses were performed. The primary outcome was the incremental cost per infection prevented, assessed from the Canadian healthcare system perspective. Envelope plus SoC was associated with fewer CIED infection (7 CIED infections/1000 patients) at higher total costs ($29 033 000/1000 patients) compared with SoC (11 CIED infections and $27 926 000/1000 patients). The incremental cost per infection prevented over 1 year was $274 416. Use of Env+SoC was cost saving only when baseline CIED infection risk was increased to 6% (vs. base case of 1.2%). CONCLUSIONS: A strategy of Env+SoC was not economically favourable compared with SoC alone, and the opportunity cost of widescale implementation should be considered. Future work is required to develop validated risk stratification tools to identify patients at greatest risk of CIED infection. The value proposition of Env+SoC improves when applying this intervention to patients at greatest infection risk.

Revision total elbow arthroplasty: Is it safe to perform a single-stage revision for presumed aseptic loosening based on clinical assessment, normal inflammatory markers, and a negative aspiration?

BACKGROUND: Revision total elbow arthroplasty (TEA) is a challenging procedure that is becoming increasingly common. In our unit, we regard it as essential to exclude infection as the underlying cause of TEA loosening. In all patients with arthroplasty loosening, we undertake a careful history and examination, perform radiographs, monitor inflammatory markers, and undertake a joint aspiration. If any investigation suggests infection as the etiology, then a 2-stage revision is undertaken. Open biopsies are not routinely performed. The aim was to ascertain from our outcomes whether it is safe to perform a single-stage revision for presumed aseptic loosening using these criteria. METHODS: A retrospective review of a consecutive series of revision TEAs was performed in our unit over a 10-year period (2008-2018). Single-stage revisions performed for presumed aseptic loosening were identified. Case notes, radiographs, bloods, aspiration results, and microbiology of tissue samples taken at revision were reviewed. RESULTS: A total of 123 revision elbow arthroplasty cases were performed in the study period. Sixty cases were revised for preoperatively proven infection, instability, or implant failure and were excluded from this study. In 63 cases, aseptic loosening was diagnosed based on history, clinical examination, blood markers, and aspiration. There were 21 dual-component and 42 single-component revisions. In the dual-component revision group, tissue samples taken at the time of revision were positive in only 1 case (5%). In the single-component revision group, positive culture samples were present in 3 cases (7%). χ2 analysis showed no significant difference between single- and dual-component revisions (P = .76). No cases with positive culture samples from either group have required subsequent revision surgery. CONCLUSION: Given the results of this study, we conclude that is safe to perform single-stage revision arthroplasty for implant loosening based on history, examination, normal inflammatory markers, and negative aspiration results without the need for open biopsy.

Incidence, Predictors, and Outcomes of Endocarditis After Transcatheter Aortic Valve Replacement in the United States.

OBJECTIVES: This study sought to evaluate the incidence and outcomes of endocarditis after transcatheter aortic valve replacement (TAVR). BACKGROUND: Data about endocarditis after TAVR are limited. METHODS: The study investigated Medicare patients who underwent TAVR from 2012 to 2017 and identified patients admitted with endocarditis during follow-up using a validated algorithm. The main study outcome was all-cause mortality. RESULTS: Of 134,717 patients who underwent TAVR, 1868 patients developed endocarditis during follow-up (incidence 0.87%/year), with majority of infections (65.0%) occurring within 1 year. Incidence of endocarditis declined in recent years. The most common organisms were Staphylococcus (22.0%), Streptococcus (20.0%), and Enterococcus (15.5%). Important predictors for endocarditis were younger age at TAVR, male sex, prior endocarditis, end-stage renal disease, repeat TAVR procedures, liver and lung disease, and post-TAVR acute kidney injury. Thirty-day and 1-year mortality were 18.5% and 45.6%, respectively. After adjusting for comorbidities and procedural complications, endocarditis after TAVR was associated with 3-fold higher risk of mortality (44.9 vs. 16.2 deaths per 100 person-years; adjusted hazard ratio [aHR]: 2.94; 95% confidence interval [CI]: 2.77 to 3.12; p < 0.0001). End-stage renal disease (aHR: 2.12; 95% CI: 1.72 to 2.60), endocarditis complicated by cardiogenic shock (aHR: 2.50, 95% CI: 1.56 to 4.02), ischemic stroke (aHR: 1.56; 95% CI: 1.07 to 2.28), intracerebral hemorrhage (aHR: 1.67; 95% CI: 1.01 to 2.76), acute kidney injury (aHR: 1.44; 95% CI: 1.27 to 1.63), blood transfusion (aHR: 1.28; 95% CI: 1.09 to 1.50), staphylococcal (aHR: 1.71; 95% CI: 1.49 to 1.97), and fungal endocarditis (aHR: 1.72; 95% CI: 1.23 to 2.39) (p < 0.05 for all) portended higher mortality following endocarditis. CONCLUSIONS: The incidence of endocarditis after TAVR is low and declining. However, it is associated with poor prognosis with one-half the patients dying within 1 year.

Pathogen influence on epidemiology, diagnostic evaluation and management of infective endocarditis.

Infective endocarditis (IE) is uncommon and has, in the past, been most often caused by viridans group streptococci (VGS). Due to the indolent nature of these organisms, the phrase 'subacute bacterial endocarditis', so-called 'SBE', was routinely used as it characterised the clinical course of most patients that extended for weeks to months. However, in more recent years, there has been a significant shift in the microbiology of IE with the emergence of staphylococci as the most frequent pathogens, and for IE due to Staphylococcus aureus, the clinical course is acute and can be associated with sepsis. Moreover, increases in IE due to enterococci have occurred and have been characterised by treatment-related complications and worse outcomes. These changes in pathogen distribution have been attributed to a diversification in the target population at risk of IE. While prosthetic valve endocarditis and history of IE remain at highest risk of IE, the rise in prevalence of injection drug use, intracardiac device implantations and other healthcare exposures have heavily contributed to the existing pool of at-risk patients. This review focuses on common IE pathogens and their impact on the clinical profile of IE.

Preliminary assessment of nanopore-based metagenomic sequencing for the diagnosis of prosthetic joint infection.

OBJECTIVES: Pathogen identification is crucial for the diagnosis and management of periprosthetic joint infection (PJI). Although culturing methods are the foundation of pathogen detection in PJI, false-negative results often occur. Oxford nanopore sequencing (ONS) is a promising alternative for detecting pathogens and providing information on their antimicrobial resistance (AMR) profiles, without culturing. METHODS: To evaluate the capability of metagenomic ONS (mONS) in detecting pathogens from PJI samples, both metagenomic next-generation sequencing (mNGS) and mONS were performed in 15 osteoarticular samples from nine consecutive PJI patients according to the modified Musculoskeletal Infection Society (MSIS) criteria. The sequencing data generated from both platforms were then analyzed for pathogen identification and AMR detection using an in-house-developed bioinformatics pipeline. RESULTS: Our results showed that mONS could be applied to detect the causative pathogen and characterize its AMR features in fresh PJI samples. By real-time sequencing and analysis, pathogen identification and AMR detection from the initiation of sequencing were accelerated. CONCLUSION: We showed proof of concept that mONS can function as a rapid, accurate tool in PJI diagnostic microbiology. Despite efforts to reduce host DNA, the high proportion of host DNA was still a limitation of this method that prevented full genome analysis.

Detection of α-defensin in synovial fluids by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry as an innovative and cost-effective assay for improved definition of periprosthetic joint infections.

RATIONALE: Detection of α-defensins in synovial fluid is gaining more and more interest in the field of correct diagnosis of periprosthetic joint infections (PJIs). At present, they can be assessed by a quantitative enzyme-linked immunosorbent assay which is expensive and time-consuming and by a qualitative lateral flow immunoassay which is rapid but quite expensive and whose clinical sensitivity is debated. Thus, developing an alternative rapid, accurate, and low-cost assay for α-defensins is important to make α-defensins actionable as novel key clinical markers. METHODS: Synovial fluid (SF) samples were obtained from 18 patients undergoing revision of primary joint arthroplasty. Of these, eight met the 2013 Musculoskeletal Infection Society (MSIS) criteria for PJIs, the remaining were classified as aseptic failure. Microbiological analysis and Synovasure assays were carried out on all samples. Sample preparation and the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) settings were adjusted to detect human neutrophil peptide (HNP)-1, -2 and -3 and to obtain optimal results in term of sensitivity and stability. RESULTS: MALDI-TOF MS was able to detect HNPs in SF from septic patients. No signals for HNPs were detected in SF from aseptic failure. The limits of detection (LOD) were 2.5 and 1.25 µg/mL for HNP-2 and HNP-1, respectively. The turnaround time of the analysis is 20 min, and SF samples are stable at -20°C for up to 3 days. Assay sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were 100% for all parameters. On the same SF samples, the Synovasure assay showed lower sensitivity specificity, and PPV and NPV of 87.5%, 90%, 87.5% and 90%, respectively. Microbiological analysis of SF confirmed the presence of bacteria only in SF MSIS-positive patients. CONCLUSIONS: The reported MALDI-TOF MS assay was able to detect and differentiate HNPs in SF samples and showed a slightly better diagnostic accuracy than the Synovasure assay.

Current Clinical Methods for Detection of Peri-Prosthetic Joint Infection.

Background: Currently, one of the most pressing problems in the field of orthopedic surgery is peri-prosthetic joint infection [PJI]. While there are numerous ways to detect PJI, current clinical detection methods differ across institutions and have varying criteria and protocols. Some of these methods include the Modified Musculoskeletal Infection Society system, culturing, polymerase chain reaction, the determination of the presence of certain biomarkers, testing for the presence of alpha defensin peptides, and leukocyte level testing. Methods: This review summarizes the most recent publications in the field of PJI detection to highlight current strengths as well as provide future directions to find the system for the quickest, cost-effective, and most accurate way to diagnose these types of infections. Results: The results of this literature review suggest that, while each method of diagnosis has its advantages, each has various drawbacks as well. Current methods can be expensive, take days to weeks to complete, be prone to contamination, and can produce ambiguous results. Conclusions: The findings in this review emphasize the need for a more comprehensive and accurate system for diagnosing PJI. In addition, the specific comparison of advantages and drawbacks can be useful for researchers and clinicians with goals of creating new diagnostic tests for PJIs, as well as in clinical scenarios to determine the correct treatment for patients.

Laboratory-based versus qualitative assessment of α-defensin in periprosthetic hip and knee infections: a systematic review and meta-analysis.

INTRODUCTION: Two methods are currently available for the assay of α-defensin: the enzyme-linked immunosorbent assay (ELISA) and the lateral flow test. We aimed to assess the diagnostic accuracy of synovial fluid α-defensin and to compare the accuracy of the laboratory-based test and the qualitative assessment for the diagnosis of hip and knee prosthetic infection. MATERIALS AND METHODS: We searched (from inception to May 2018) MEDLINE, Scopus, EMBASE, Web of Science, and Cochrane for studies on α-defensin in the diagnosis of periprosthetic joint infection (PJI). Sensitivity, specificity, positive and negative likelihood ratio (LR), and diagnostic odds ratio were analyzed using the bivariate diagnostic random-effects model. The receiver-operating curve for each method was calculated. RESULTS: We included 13 articles in our meta-analysis, including 1170 patients who underwent total hip and knee arthroplasties revision; 368 (31%) had a joint infection according to MSIS and MSIS-modified criteria. Considering the false-positive result rate of 8% and false-negative result rate of 3%, pooled sensitivity and specificity were 0.90 (95% CI 0.83-0.94) and 0.95 (0.92-0.96), respectively. The area under the curve (AUC) was 0.94 (0.92-0.94). No statistical differences in terms of sensitivity and specificity were found between the laboratory-based and qualitative test. The pooled sensitivity and specificity of the two alpha-defensin assessment methods were: laboratory-based test 0.97 (95% CI 0.93-0.99) and 0.96 (95% CI 0.94-0.98), respectively; qualitative test 0.83 (95% CI 0.73-0.91) and 0.94 (95% CI 0.89-0.97), respectively. The diagnostic odds ratio of the α-defensin laboratory based was superior to that of the qualitative test (1126.085, 95% CI 352.172-3600.702 versus 100.9, 95% CI 30.1-338.41; p < 0.001). The AUC for immunoassay and qualitative tests was 0.97 (0.95-0.99) and 0.91 (0.88-0.99), respectively. CONCLUSION: Detection of α-defensin is an accurate test for diagnosis of hip and knee prosthetic infections. The diagnostic accuracy of the two alpha-defensin assessment methods is comparable. The lateral flow assay is a valid, rapid, and more available diagnostic tool, particularly to rule out PJI.

2018 International Consensus Meeting on Musculoskeletal Infection: Research Priorities from the General Assembly Questions.

Musculoskeletal infections (MSKI) remain the bane of orthopedic surgery, and result in grievous illness and inordinate costs that threaten healthcare systems. As prevention, diagnosis, and treatment has remained largely unchanged over the last 50 years, a 2nd International Consensus Meeting on Musculoskeletal Infection (ICM 2018, https://icmphilly.com) was completed. Questions pertaining to all areas of MSKI were extensively researched to prepare recommendations, which were discussed and voted on by the delegates using the Delphi methodology. The questions, including the General Assembly (GA) results, have been published (GA questions). However, as critical outcomes include: (i) incidence and cost data that substantiate the problems, and (ii) establishment of research priorities; an ICM 2018 research workgroup (RW) was assembled to accomplish these tasks. Here, we present the result of the RW consensus on the current and projected incidence of infection, and the costs per patient, for all orthopedic subspecialties, which range from 0.1% to 30%, and $17,000 to $150,000. The RW also identified the most important research questions. The Delphi methodology was utilized to initially derive four objective criteria to define a subset of the 164 GA questions that are high priority for future research. Thirty-eight questions (23% of all GA questions) achieved the requisite > 70% agreement vote, and are highlighted in this Consensus article within six thematic categories: acute versus chronic infection, host immunity, antibiotics, diagnosis, research caveats, and modifiable factors. Finally, the RW emphasizes that without appropriate funding to address these high priority research questions, a 3rd ICM on MSKI to address similar issues at greater cost is inevitable.

Incidence, Management, and Outcomes of Aortic Graft Infection.

BACKGROUND: Infection complicates 1% of aortic grafts, and although uncommon, the associated morbidity and mortality are significant. We sought to determine risk factors for aortic graft infection (AGI), the long-term outcomes in patients managed both nonoperatively and via explantation. METHODS: This observational study reviewed sequential aortic grafts (thoracic or abdominal) inserted via open or endovascular means between 2000 and 2017. We used Cox proportional hazards regression analyses to compare risk factors between groups who did and did not acquire an AGI and recorded method of management, morbidity, mortality, and duration to adverse event. RESULTS: There were 883 aortic repairs, 49% were endovascular. 17.2% were for ruptured aneurysms, 1.1% for symptomatic aneurysms, 1.4% for type B dissections, and 0.5% for occlusive disease. Twelve patients presented with AGI, of which ten had their index procedure performed at our institution (AGI incidence of 1.1%). There was no difference in rates of AGI between open and endovascular repairs (0.9 vs. 1.4%, P = 0.24). AGI was significantly associated with emergency aortic repair (HR 3.63, 95% CI 1.13-11.57, P = 0.03), septic process requiring in-patient management during follow-up (HR 5.44, 95% CI 1.21-24.26, P = 0.02), and suprarenal clamping during open repair (HR 5.21, 95% CI 1.00-26.99, P = 0.05). Four patients were managed with explantation and revascularization (3 extra-anatomical bypasses) and remained well at a median follow-up of 46 months. Of the 8 patients managed nonoperatively, 4 died at an average of 13.5 days after representation, and the other 4 remained well on oral antibiotics at a median follow-up of 26.5 months. No patient suffered limb loss, and there was no change in the rate of infection over the period. CONCLUSIONS: Incidence of AGI remains low but is associated with significant mortality. Patients with aortic grafts in situ require aggressive treatment of septic foci to prevent graft infection.

Next-Generation Sequencing vs Culture-Based Methods for Diagnosing Periprosthetic Joint Infection After Total Knee Arthroplasty: A Cost-Effectiveness Analysis.

BACKGROUND: Periprosthetic joint infection (PJI) after total knee arthroplasty is challenging to diagnose. Compared with culture-based techniques, next-generation sequencing (NGS) is more sensitive for identifying organisms but is also less specific and more expensive. To date, there has been no study comparing the cost-effectiveness of these two methods to diagnose PJI after total knee arthroplasty. METHODS: A Markov, state-transition model projecting lifetime costs and quality-adjusted life years (QALYs) was constructed to determine the cost-effectiveness from a societal perspective. The primary outcome was incremental cost-effectiveness ratio, with a willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses were performed to evaluate parameter assumptions. RESULTS: At our base case values, culture was not determined to be cost-effective compared to NGS, with an incremental cost-effectiveness ratio of $422,784 per QALY. One-way sensitivity analyses found NGS to be the cost-effective choice above a pretest probability of 45.5% for PJI. In addition, NGS was cost-effective if its sensitivity was greater than 70.0% and its specificity greater than 94.1%. Two-way sensitivity analyses revealed that the pretest probability and test performance parameters (sensitivity and specificity) were the largest factors for identifying whether a particular strategy was cost-effective. CONCLUSION: The results of our model suggest that the cost-effectiveness of NGS to diagnose PJI depends primarily on the pretest probability of PJI and the performance characteristics of the NGS technology. Our results are consistent with the idea that NGS should be reserved for clinical contexts with a high pretest probability of PJI. Further study is required to determine the indications and subgroups for which NGS offers clinical benefit.