The diagnosis of periprosthetic joint infection (PJI) is difficult and requires a battery of tests and clinical findings. The purpose of this review is to summarize all current evidence for common ...and new serum biomarkers utilized in the diagnosis of PJI.
We searched two literature databases, using terms that encompass all hip and knee arthroplasty procedures, as well as PJI and statistical terms reflecting diagnostic parameters. The findings are summarized as a narrative review.
Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were the two most commonly published serum biomarkers. Most evidence did not identify other serum biomarkers that are clearly superior to ESR and CRP. Other serum biomarkers have not demonstrated superior sensitivity and have failed to replace CRP and ESR as first-line screening tests. D-dimer appears to be a promising biomarker, but more research is necessary. Factors that influence serum biomarkers include temporal trends, stage of revision, and implant-related factors (metallosis).
Our review helped to identify factors that can influence serum biomarkers' level changes; the recognition of such factors can help improve their diagnostic utility. As such, we cannot rely on ESR and CRP alone for the diagnosis of PJI prior to second-stage reimplantation, or in metal-on-metal or corrosion cases. The future of serum biomarkers will likely shift towards using genomics and proteomics to identify proteins transcribed via messenger RNA in response to infection and sepsis.
2018;7:85-93.
Long-term acute care hospitals are an option for patients in intensive care units who require prolonged care after an acute illness. Predicting use of these facilities may help hospitals improve ...resource management, expenditures, and quality of care delivered in intensive care.
To develop a predictive tool for early identification of intensive care patients with increased probability of transfer to such a hospital.
Data on 1967 adults admitted to intensive care at a tertiary care hospital between January 2009 and June 2009 were retrospectively reviewed. The prediction model was developed by using multiple ordinal logistic regression. The model was internally validated via the bootstrapping technique and externally validated with a control cohort of 950 intensive care patients.
Among the study group, 146 patients (7.4%) were discharged to long-term acute care hospitals and 1582 (80.4%) to home or other care facilities; 239 (12.2%) died in the intensive care unit. The final prediction algorithm showed good accuracy (bias-corrected concordance index, 0.825; 95% CI, 0.803-0.845), excellent calibration, and external validation (concordance index, 0.789; 95% CI, 0.754-0.824). Hypoalbuminemia was the greatest potential driver of increased likelihood of discharge to a long-term acute care hospital. Other important predictors were intensive care unit category, older age, extended hospital stay before admission to intensive care, severe pressure ulcers, admission source, and dependency on mechanical ventilation.
This new predictive tool can help estimate on the first day of admission to intensive care the likelihood of a patient's discharge to a long-term acute care hospital.
Prosthetic joint infection (PJI) is a serious complication after total joint arthroplasty (TJA). Chlorhexidine is a widely used antiseptic because of its rapid and persistent action. It is well ...tolerated and available in different formulations at various concentrations. Chlorhexidine can be used for pre-operative skin cleansing, surgical site preparation, hand antisepsis of the surgical team and intra-articular irrigation of infected joints. The optimal intra-articular concentration of chlorhexidine gluconate in irrigation solution is 2%, to provide a persistent decrease in biofilm formation, though cytotoxicity might be an issue. Although chlorhexidine is relatively cheap, routine use of chlorhexidine without evidence of clear benefits can lead to unnecessary costs, adverse effects and even emergence of resistance. This review focuses on the current applications of various chlorhexidine formulations in TJA. As the treatment of PJI is challenging and expensive, effective preparations of chlorhexidine could help in the prevention and control of PJI.
The translation of well-established molecular biology methods such as genetic coding, selection, and DNA sequencing to combinatorial organic chemistry and compound identification has made extremely ...large compound collections, termed DNA-encoded libraries, accessible for drug screening. However, the reactivity of the DNA imposes limitations on the choice of chemical methods for encoded library synthesis. For example, strongly acidic reaction conditions must be avoided because they damage the DNA by depurination, i.e. the cleavage of purine bases from the oligomer. Application of micellar catalysis holds much promise for encoded chemistry. Aqueous micellar dispersions enabled compound synthesis under often appealingly mild conditions. Amphiphilic block copolymers covalently functionalized with sulfonic acid moieties in the lipophilic portion assemble in water and locate the Brønsted catalyst in micelles. These acid nanoreactors enabled the reaction of DNA-conjugated aldehydes to diverse substituted tetrahydroquinolines and aminoimidazopyridines by Povarov and Groebke–Blackburn–Bienaymé reactions, respectively, and the cleavage of tBoc protective groups from amines. The polymer micelle design was successfully translated to the Cu/Bipyridine/TEMPO system mediating the oxidation of DNA-coupled alcohols to the corresponding aldehydes. These results suggest a potentially broad applicability of polymer micelles for encoded chemistry.
Periprosthetic joint infection (PJI) is one of the most devastating complications of total joint arthroplasty. The underlying pathogenesis involves the formation of bacterial biofilm that protects ...the pathogen from the host immune response and antibiotics, making eradication difficult. The aim of this study was to develop a rabbit model of knee PJI that would allow reliable biofilm quantification and permit the study of treatments for PJI. In this work, New Zealand white rabbits (
) underwent knee joint arthrotomy, titanium tibial implant insertion, and inoculation with Xen36 (bioluminescent
) or a saline control after capsule closure. Biofilm was quantified via scanning electron microscopy (SEM) of the tibial explant 14 d after inoculation (
noninfected,
infected). Rabbits underwent debridement, antibiotics, and implant retention (DAIR) (
) or sham surgery (
noninfected,
infected) 14 d after inoculation, and they were sacrificed 14 d post-treatment. Tibial explant and periprosthetic tissues were examined for infection. Laboratory assays supported bacterial infection in infected animals. No differences in weight or C-reactive protein (CRP) were detected after DAIR compared to sham treatment. Biofilm coverage was significantly decreased with DAIR treatment when compared with sham treatment (61.4 % vs. 90.1 %,
.0011) and was absent in noninfected control explants. In summary, we have developed an experimental rabbit hemiarthroplasty knee PJI model with bacterial infection that reliably produces quantifiable biofilm and provides an opportunity to introduce treatments at 14 d. This model may be used to better understand the pathogenesis of this condition and to measure treatment strategies for PJI.
Abstract Studies conflict regarding the impact of psychiatric illnesses including depression, anxiety, dementia and schizophrenia on perioperative outcomes following total hip (THA) and knee ...arthroplasty (TKA). Psychiatric comorbidity incidence, in-hospital adverse events, discharge disposition, and mortality were assessed for THA or TKA patients between 1990 and 2007 using the US National Hospital Discharge Survey. A cohort representative of 8,379,490 patients was identified and analyzed using multivariable regression analysis. Diagnoses of depression, dementia and schizophrenia were associated with increased odds of adverse events ( P < 0.001). Schizophrenia and depression were associated with higher odds of perioperative blood transfusion ( P < 0.001). All psychiatric comorbidities were associated with higher odds of non-routine discharge ( P < 0.001). Diagnosis of dementia was associated with higher in-hospital mortality ( P < 0.001).
DNA‐encoded combinatorial synthesis provides efficient and dense coverage of chemical space around privileged molecular structures. The indole side chain of tryptophan plays a prominent role in key, ...or “hot spot”, regions of protein–protein interactions. A DNA‐encoded combinatorial peptoid library was designed based on the Ugi four‐component reaction by employing tryptophan‐mimetic indole side chains to probe the surface of target proteins. Several peptoids were synthesized on a chemically stable hexathymidine adapter oligonucleotide “hexT”, encoded by DNA sequences, and substituted by azide‐alkyne cycloaddition to yield a library of 8112 molecules. Selection experiments for the tumor‐relevant proteins MDM2 and TEAD4 yielded MDM2 binders and a novel class of TEAD‐YAP interaction inhibitors that perturbed the expression of a gene under the control of these Hippo pathway effectors.
A focused approach: A DNA‐encoded peptoid library was designed by the Ugi multicomponent reaction around indole structures that mimic the side chain of tryptophan. Applying this focused library to the challenging cancer targets MDM2 and hTEAD4 yielded compounds for inhibitor development. Compounds binding to hTEAD4 disrupted the hTEAD4–YAP interaction, and reduced expression of a gene under control of the TEAD–YAP transcription factor complex.
Understanding the ligandability of a target protein, defined as the capability of a protein to bind drug‐like compounds on any site, can give important stimuli to drug‐development projects. For ...instance, inhibition of protein–protein interactions usually depends on the identification of protein surface binders. DNA‐encoded chemical libraries (DELs) allow scanning of protein surfaces with large chemical space. Encoded library selection screens uncovered several protein–protein interaction inhibitors and compounds binding to the surface of G protein‐coupled receptors (GPCRs) and kinases. The protein surface‐binding chemotypes from DELs are predominantly chemically modified and cyclized peptides, and functional small‐molecule peptidomimetics. Peptoid libraries and structural peptidomimetics have been less studied in the DEL field, hinting at hitherto less populated chemical space and suggesting alternative library designs. Roughly a third of bioactive molecules evolved from smaller, target‐focused libraries. They showcase the potential of encoded libraries to identify more potent molecules from weak, for example, fragment‐like, starting points.
DELving into the library: Protein surface binders include chemically modified peptides and functional peptidomimetics acting as protein–protein interaction inhibitors and compounds binding to the surface of GPCRs and kinases. Several such compounds have been identified from focused libraries, thus showing the utility of DNA‐encoded chemical libraries (DELs) for improving the potency of weak, say, fragment‐like, starting points.
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