Periprosthetic Tissue Research Articles

A Postmortem Analysis of Polyethylene Damage and Periprosthetic Tissue in Rotating Platform and Fixed Bearing Tibial Inserts.

Mobile bearing designs are intended to reduce wear, but mixed results were reported from retrieval analyses. Postmortem evaluation (PM) provides the opportunity to assess polyethylene damage in successful implants. We compared damage patterns, MRI presentation, and histology between mobile-bearing and fixed tibial inserts retrieved postmortem and compared these results to our prior findings from implants retrieved at revision. Eleven postmortem knees with rotating platform (RP) implants and 13 with fixed bearing (FB) implants were examined. All were MRI scanned, and tissue samples were collected from standardized regions for histology. Polyethylene inserts were subjectively scored to assess articular, backside, and PS post surfaces for damage modes and severity. Average duration of implantation was 9.3 years (1.7-19.6 years). Surface burnishing was the most common polyethylene damage mode. Average damage scores were higher for RP (53.4) compared to FB inserts (34.4) due to greater backside damage (13.4 for RP vs 1.4 for FB). A minimal difference in damage was observed on the articular surfaces (37.4 RP vs 30.0 FB). Mild innate macrophage reactions were seen in 8 (72.7%) RP and 5 (45.5%) FB specimens. Polyethylene particles were identified in 7 (63.6%) RP and 3 (27.7%) FB specimens. Postmortem inserts showed low damage levels and mild tissue reactions compared to those reported for implants removed at revision arthroplasty. Nonetheless, trends in comparing RP and FB inserts were consistent with those seen in retrieval analyses, demonstrating the usefulness of retrieval studies in capturing performance differences among TKA designs.

Mixed material wear particle isolation from periprosthetic tissue surrounding total joint replacements.

Submicron‐sized wear particles are generally accepted as a potential cause of aseptic loosening when produced in sufficient volumes. With the accelerating use of increasingly wear‐resistant biomaterials, identifying such particles and evaluating their biological response is becoming more challenging. Highly sensitive wear particle isolation methods have been developed but these methods cannot isolate the complete spectrum of particle types present in individual tissue samples. Two established techniques were modified to create one novel method to isolate both high‐ and low‐density materials from periprosthetic tissue samples. Ten total hip replacement and eight total knee replacement tissue samples were processed. All particle types were characterized using high resolution scanning electron microscopy. UHMWPE and a range of high‐density materials were isolated from all tissue samples, including: polymethylmethacrylate, zirconium dioxide, titanium alloy, cobalt chromium alloy and stainless steel. This feasibility study demonstrates the coexistence of mixed particle types in periprosthetic tissues and provides researchers with high‐resolution images of clinically relevant wear particles that could be used as a reference for future in vitro biological response studies.

A novel method to improve femoral head and stem taper stability intraoperatively in total hip arthroplasty – a proof of concept study

BackgroundMechanically assisted crevice corrosion (MACC) has been associated with the compromised durability and fixation of modular total hip implants, adverse reaction of local tissue, and other undesirable clinical outcomes in total hip arthroplasty (THA). MACC is primarily caused by the relative motion between the femoral head and stem. To minimize the relative motion the taper connection between the two components must be strong enough. The current study addressed the following questions: (1) Does increasing the mass of the femoral stem improve the taper connection strength intraoperatively? (2) Does increasing the mass of the femoral stem reduce the risk of periprosthetic tissue damage intraoperatively? HypothesisIncreasing the mass of the femoral stem improve the taper connection strength intraoperatively. Materials and methodsDuring the experiment, femoral heads were impacted onto the stem tapers with and without an additional weight attached to the stem. The femoral heads were then pulled off to investigate the strength of the taper connection. The stem displacement and acceleration at impaction were also measured to evaluate the risk of periprosthetic tissue damage. ResultsThe results showed that the pull-off force was increased by 24% (p=0.011, n=6) when an additional weight was attached to the stem. The additional weight also reduced the maximum stem acceleration and maximum stem displacement by 37% (p<0.001, n=6) and 14% (p=0.094, n=6), respectively. DiscussionThese findings suggest that the femoral head and stem taper connection strength can be significantly improved and the risk of periprosthetic tissue damage significantly reduced intraoperatively by attaching an additional weight to the stem to increase its mass. Level of evidenceIII, comparative in vitro mechanical investigation.

Standardized quantification of biofilm in a novel rabbit model of periprosthetic joint infection.

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 Staphylococcus aureus) 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.

Positivity Trends of Bacterial Cultures from Cases of Acute and Chronic Periprosthetic Joint Infections.

Background: There is no clear distinction in the literature regarding the positivity trends of bacterial cultures in acute and chronic prosthetic joint infections. Methods: We prospectively included in this study all consecutive patients, aged over 18 years, that were hospitalized from September 2016 through December 2019, that underwent a joint arthroplasty revision surgery. Results: Forty patients were included in our analysis, 11 acute/acute hematogenous and 29 chronic PJIs. We were able to identify all strains of acute/acute hematogenous PJIs within 3 days, whereas this took 8 days for chronic PJIs. Sonication fluid cultures increased the positivity rate and helped in identifying rare pathogens such as Ralstonia pickettii from chronic PJIs, but also increased the number of identified strains from acute PJIs. Culturing synovial fluid in our study did not seem to have a clear benefit compared to sonication fluid and periprosthetic tissue cultures. Conclusion: There was a different positivity trend in bacterial cultures. Empiric broad-spectrum antibiotic therapy can be re-evaluated after 3 days for acute PJIs. A prolonged incubation time, especially in the case of chronic PJIs, is mandatory; however, extending the incubation period beyond 14 days would not further improve the ability to identify microorganisms.

Diagnostic value of open incisional biopsies in suspected, difficult-to-diagnose periprosthetic hip joint infection prior to revision surgery

IntroductionPrior to revision of total hip arthroplasty (THA), low-grade chronic periprosthetic joint infection (PJI) is often difficult to diagnose. We aimed to determine the diagnostic accuracy of open incisional tissue biopsy for the prediction of PJI prior to THA revision in cases with culture-negative or dry tap joint aspirates.Materials and methodsThis retrospective single-center study includes 32 consecutive THA revision cases with high clinical suspicion of low-grade chronic PJI of the hip with culture-negative or dry tap joint aspirates and without systemic signs of infection. Open incisional biopsy (OIB) was performed prior to revision surgery. Periprosthetic tissue samples were analyzed by microbiology and histopathology for PJI. During definitive revision arthroplasty, identical diagnostics were repeated. Results from both procedures were compared and sensitivity, specificity, positive and negative predictive values of OIB for the final diagnosis were calculated.ResultsAverage age at revision was 69.3 ± 13.5 years. The sensitivity of the OIB procedure was 80% (microbiology), 69% (histology) and 82% for combined analyses (microbiology and histology). Specificity of OIB was 80% (microbiology), 94% (histology) and 60% for combined analyses.ConclusionsOpen tissue biopsy performed in cases with culture-negative or inconclusive synovial fluid aspirates prior to revision of THA has limited diagnostic accuracy for the prediction of PJI. The procedure does not reliably close the diagnostic gap in a substantial number of cases. In this difficult patient population, risk of an open procedure may outweigh benefits and alternative less invasive methods should be considered for the preoperative diagnosis of PJI.

Lymphocyte Subset Ratio Cannot Diagnose Immune Failure of a TKA

BackgroundUp to 20% of patients are dissatisfied following total knee arthroplasty (TKA), most often due to pain and/or stiffness. The differential diagnosis includes immune reaction to the prosthesis. However, there is no consensus on diagnostic criteria for immune failure, an allergic reaction, to a TKA.Histologic evaluation could provide evidence as to whether an allergic reaction caused TKA failure. A recent study showed an increase in CD4+ lymphocytes compared to CD8+ lymphocytes in patients lymphocyte transformation testing (LTT) + for Ni. This finding is consistent with Ni sensitization, but can lymphocyte subsets be used to diagnose immune failure on a case-by-case basis? MethodsPeriprosthetic tissues from 18 revision cases of well-fixed, aseptic, but painful and/or stiff primary TKAs were analyzed. Six patients LTT− for Ni were matched as a cohort for age, sex, and body mass index (BMI), to 12 patients LTT + for Ni. Periprosthetic tissue biopsies underwent immunohistochemical IHC staining for CD4+ and CD8+ lymphocyte subsets and were compared by LTT status. The immunohistochemicalIHC results were also compared with periprosthetic histology. ResultsThere was no relationship between LTT status and mean CD4+ cells/hpf or CD4+:CD8+ lymphocyte ratio. No relationship was found between LTT stimulation index (continuous or categorical) and CD4+:CD8+ ratio or aseptic lymphocyte-dominant vasculitis-associated lesion ALVAL score. ConclusionLymphocytes in periprosthetic tissue are highly variable in number, subtype ratio, and location, and have no relationship to LTT result or ALVAL score on a case-by-case basis. Based on these results, lymphocyte subsets cannot diagnose immune failure. Further work is needed to determine criteria for the diagnosis of immune failure of a TKA.

Dental and Orthopaedic Implant Loosening: Overlap in Gene Expression Regulation.

ObjectivesEndoprosthetic loosening still plays a major role in orthopaedic and dental surgery and includes various cellular immune processes within peri-implant tissues. Although the dental and orthopaedic processes vary in certain parts, the clinical question arises whether there are common immune regulators of implant loosening. Analyzing the key gene expressions common to both processes reveals the mechanisms of osteoclastogenesis within periprosthetic tissues of orthopaedic and dental origin.MethodsDonor peripheral blood mononuclear cells (PBMCs) and intraoperatively obtained periprosthetic fibroblast-like cells (PPFs) were (co-)cultured with [± macrophage-colony stimulating factor (MCSF) and Receptor Activator of NF-κB ligand (RANKL)] in transwell and monolayer culture systems and examined for osteoclastogenic regulations [MCSF, RANKL, osteoprotegerin (OPG), and tumor necrosis factor alpha (TNFα)] as well as the ability of bone resorption. Sequencing analysis compared dental and orthopaedic (co-)cultures.ResultsMonolayer co-cultures of both origins expressed high levels of OPG, resulting in inhibition of osteolysis shown by resorption assay on dentin. The high OPG-expression, low RANKL/OPG ratios and a resulting inhibition of osteolysis were displayed by dental and orthopaedic PPFs in monolayer even in the presence of MCSF and RANKL, acting as osteoprotective and immunoregulatory cells. The osteoprotective function was only observed in monolayer cultures of dental and orthopaedic periprosthetic cells and downregulated in the transwell system. In transwell co-cultures of PBMCs/PPFs profound changes of gene expression, with a significant decrease of OPG (20-fold dental versus 100 fold orthopaedic), were identified. Within transwell cultures, which offer more in vivo like conditions, RANKL/OPG ratios displayed similar high levels to the original periprosthetic tissue. For dental and orthopaedic implant loosening, overlapping findings in principal component and heatmap analysis were identified.ConclusionsThus, periprosthetic osteoclastogenesis may be a correlating immune process in orthopaedic and dental implant failure leading to comparable reactions with regard to osteoclast formation. The transwell cultures system may provide an in vivo like model for the exploration of orthopaedic and dental implant loosening.

Immune checkpoint upregulation in periprosthetic joint infection.

Periprosthetic joint infections (PJI) induce an immunosuppressive cytokine profile through an unknown mechanism. Immune checkpoints, like programmed cell death 1 (PD-1) and its ligand (PD-L1), initiate innate immunosuppressive pathways essential for self-tolerance. Several malignancies and chronic infections co-opt these pathways to derive a survival advantage. This study evaluates PD-1/PD-L1 expression in periprosthetic tissue from patients undergoing revision hip or knee arthroplasty for a PJI versus an aseptic failure. PD-1/PD-L1 in the global tissue sample and the high-power microscopic field of maximum expression was analyzed prospectively using immunohistochemistry. Fifteen patients with a PJI (45%) and 16 patients with an aseptic failure (52%) were included. PD-1 expression was uniformly low. Maximum PD-L1 expression was upregulated in patients with a PJI (25%, interquartile range [IQR]: 5%-75%) versus an aseptic failure, (8%, IQR: 1%-48%, p = 0.039). In the PJI cohort, maximum PD-L1 expression was higher among patients who developed a recurrent PJI (68%, IQR: 53%-86% vs. 15%, IQR: 5%-70%, p = 0.039). Patients with global PD-L1 over 5% trended toward a near 22-fold increase in the odds of reinfection (odds ratio [OR]: 21.9, 95% confidence interval [CI]: 0.9-523.5, p = 0.057) and patients with maximum PD-L1 over 20% trended toward a 15-fold increase in the odds of reinfection (OR: 15.0, 95% CI: 0.6-348.9, p = 0.092). These results support immune checkpoint upregulation as a mechanism of PJI-induced local immune dysfunction. Future studies should confirm PD-L1 as a risk factor for reinfection in larger cohorts.

Inflammatory tissue reactions around aseptically loose cemented hip prostheses: A retrieval study of the Spectron EF stem with Reflection All-Poly acetabular cup.

The cemented Spectron EF stem in combination with the cemented non‐crosslinked Reflection All‐Poly cup showed a high rate of mid‐term aseptic loosening. However, the failure mechanisms are not fully known. We assessed the inflammatory tissue reactions and wear particles in periprosthetic tissues, implant wear and blood metal ion levels in 28 patients with failed implants. Histological analysis showed a macrophage pre‐dominant pattern with randomly distributed lymphocytes, with various amounts of neutrophils and giant cells. The number of different cell types in the tissue samples from patients in the cup group and in the stem group was similar. Wear particles, mainly ZrO2, CoCrMo, and polyethylene particles of different sizes and shapes, were associated with macrophages/giant cells, and total particle load/mm2 was higher in cases of stem loosening. The Spectron EF stems were heavily worn, abraded, and polished. Stem abrasion correlated with metal ion concentrations in blood. The median polyethylene wear rate of the Reflection cups was 0.23 mm/year. The high proximal roughness of the Spectron EF stem resulted in excessive cement wear during loosening. The resulting inflammatory tissue responses to the degradation products both from the cup and the stem led to massive osteolysis and subsequent implant loosening.

Determination of Incidence of Soft Tissue Reactions after Total Hip Replacement using Elastography and Role of Elastography in Screening of Periprosthetic Soft Tissue: A Prospective Observational Study

Introduction: Adverse local tissue reactions after Total Hip Replacement (THR) have been widely described in literature recently as a course of aseptic loosening. Evaluation for any adverse soft tissue reactions is challenging with traditional imaging techniques like Magnetic Resonance Imaging (MRI), and are limited, due to production of metallic artifact. Ultrasound, specifically its refined form elastography, has emerged recently as a useful tool for assessing the soft tissues. Aim: To determine the incidence of soft tissue reactions in cases of THR and to evaluate role of elastography in assessment of periprosthetic soft tissue. Materials and Methods: This prospective observational study was conducted in the Department of Orthopaedics, Dr. Hardas Singh Orthopaedic Hospital, Amritsar, Punjab, India, from May 2013 to April 2014. Study comprises of consecutively followedup 66 hips which were evaluated and assessed clinically and radiologically using ultrasound elastography for periprosthetic soft tissue and degree of fibrosis. The MRI was done in patients with positive findings only. Diagnosis was then confirmed with biopsy in patients who underwent revision surgery. Incidence of clinical symptoms, implant loosening, stability of implant, various types of soft tissue reactions, pseudotumour formation and synovial hypertrophy were determined and association between clinical and radiological findings was done. Chi-square test was determined to see the statistical significance. Results: Total of 66 hips were studied in 60 patients with mean age of 56.08±16.55 years (26-95 years). The incidence of soft tissue reactions observed in the study was 83.3% (n=55), of all 66 hips 36 were symptomatic, Implant loosening was seen in 29 hips, pseudotumours were detected in 3 (4.5%) hips, cystic nodules in 2 (3.0%) hips, enlarged lymph nodes in one (1.5%) hip, fibrogranuloma in 2 (3%) hips and synovial thickening was seen in 12 hips. Association of Harris Hip Score with capsular thickness, implant stability and acetabular loosening was found to be statistically significant. Conclusion: The study shows a substantially higher incidence of soft tissue reaction and capsular hypertrophy following THR. Ultrasound elastography is a good screening tool to detect early soft tissue changes in periprosthetic tissue.

The Unusual Cause of Prosthetic Joint Infection: Outcomes of Nontuberculous Mycobacteria Treatment Following Primary Total Knee Arthroplasty.

Nontuberculous mycobacterium (NTM) is a rare cause of prosthetic joint infection (PJI) following primary total knee arthroplasty (TKA). NTM causes a variety of infections, mainly divided into pulmonary and extrapulmonary infections. In Pakistan, there was a 7.7-fold increase in NTM infections from 21 cases in 2012 to 163 cases in 2018. An earlier study evaluating the distribution of NTM species across Pakistan suggested geographical variation across different regions, every area having its own distribution spectrum. There are no data available especially in developing countries such as Pakistan regarding PJI due to NTM following primary TKA. The purpose of our study was to determine treatment outcomes of two-stage revision surgery following NTM infection. This is a retrospective study. Patients who underwent TKA between June 2008 and December 2018 were included in the study. NTM was defined as the presence of traditional criteria for diagnosing PJI plus growth of NTM cultured from a joint aspirate or deep periprosthetic tissue specimen using Löwenstein-Jensen medium and Mycobacteria Growth Indicator Tube medium. All patients were female with a mean age of 62.8 ± 7.9 years. The mean body mass index was 25.6 ± 2.8 kg/m2. Treatment outcomes were categorized into favorable and unfavorable. We found rapid-growing mycobacterium in 6 patients whereas slow-growing mycobacterium was found in 2 patients only. Generally, clarithromycin was the standard antibiotic used in all cases of NTM infections. All patients underwent revision surgery. Meticulous surgical debridement and prolonged antibiotic treatment course were the only hope of cure to combat the unusual cause of PJI following primary TKA.

Revision Stapedotomies: The Role of Periprosthetic Scar Tissue Formation in the Development of Unsatisfactory Hearing Results after Stapedotomy.

Introduction Revision stapes surgeries are difficult to perform, and their audiological results are inferior to primary surgeries. Objective Our goal was to identify the most common and most influential postoperative reasons that cause persistent air-bone gap (ABG) after the primary surgery. Our focus was concentrated on the mechanical dysfunctions in the middle ear, with special regard to postoperative adhesion formation. Methods We performed a retrospective case series study with 23 cases that underwent revision stapedotomies. Results A significant improvement was seen in ABG and air conduction levels after surgery. The periprosthetic adhesion formation was seen in 65% of the cases, and it was the primary cause behind the unsatisfactory hearing result in 30% of cases. There was no significant difference in the level of persistent ABGs after the primary surgery, in case of the intratympanic adhesion presence, compared with the presence of other surgical failures. Concerning hearing and ABG gain after revision surgery, the non-inferiority of the negative effect associated with adhesion was shown compared with the other reasons. Conclusion The revision stapedotomy is an efficient treatment option in case of persistent ABG. Periprosthetic adhesions are the most common intratympanic reasons for compromised audiological outcomes after stapedotomy. Adhesion formations have the same negative effect on ABG development as any other surgical failure, and the revision could be more challenging in these cases. These findings highlight the use of the most atraumatic surgical technique and preservation of intact intratympanic mucosa during middle ear surgery.

Bone protein analysis via label-free quantitative proteomics in patients with periprosthetic joint infection

Periprosthetic joint infection (PJI) is a catastrophic complication of arthroplasty. The treatment of PJI often requires multiple operations and long-term use of antibiotics, making PJI a substantial health and economic burden for patients. Therefore, there is an urgent need to elucidate the pathological mechanism of PJI to explore new therapeutic methods. This study aimed to explore proteomics changes in bone tissue around the prosthesis during PJI development, to explain the pathological mechanism and to provide new treatment ideas. Ten patients who underwent revision surgery at our institution were included: 5 patients with Staphylococcus aureus PJI and 5 patients with aseptic failure. The proteomics changes in bone tissues after PJI were investigated by label-free quantitative proteomics, and the pathways affected by the differential proteins were analyzed by GO annotation, GO enrichment analysis, KEGG enrichment analysis and protein-protein interaction network analysis. We identified 435 differentially expressed proteins (DEPs), with 213 upregulated and 222 downregulated proteins. Analysis revealed activation of immune-related pathways, such as complement and coagulation cascades, phagocytosis, and neutrophil activation, and inhibition of energy metabolism pathways represented by the TCA cycle. We also observed an altered balance between osteoblasts and osteoclasts during S. aureus PJI. We hope that these processes will reveal new treatment ideas. SignificancePJI is a catastrophic complication of arthroplasty. When infection occurs, bacteria may invade periprosthetic bone tissue to escape immunity and cause damage. So far, only few studies focused on the changes of proteomics associated to PJI. This is the first study to describe the proteomics changes of periprosthetic bone tissue of patients with PJI. We found that the pathological process of S. aureus PJI mainly involves activation of the immune system, decreased energy metabolism, and an altered balance of osteoblasts and osteoclasts.

Monitoring the reduction and maintenance of periprosthetic bone tissue in cementless primary hip endoprosthesis with alendronate therapy

Loss of periprosthetic bone tissue in primary hip endoprostheses is common in clinical practice. This loss can be progressive and in extreme conditions can jeopardize the longevity of the prosthesis. In order to monitor the function of Alendronate therapy for bone maintenance, the study included 50 patients with implanted total cement-free hip endoprosthesis (TPH). The first group of 25 patients received Alendronate, calcium and vitamin D3 orally postoperatively. The second group of 25 patients were examined postoperatively without therapy. Patients were followed by radiographic and dual-energy X-ray absorptiometry (DXA) at 6 and 12 months. The study showed that in patients with TPH there was a difference in the X-ray findings as well as occurrence of osteolysis in certain Gruen zones, which was confirmed by changes in the state of bone mineral density (BMD) and bone mineral content (BMC) in the interval between 6 and 12 months using the DXA method. Alendronate therapy after TPH implantation allows reduction of periprosthetic bone mass loss, maintenance of bone mineralization and implant hardening.

Driving electrochemical corrosion of implanted CoCrMo metal via oscillatory electric fields without mechanical wear

Decades of research have been dedicated to understanding the corrosion mechanisms of metal based implanted prosthetics utilized in modern surgical procedures. Focused primarily on mechanically driven wear, current fretting and crevice corrosion investigations have yet to precisely replicate the complex chemical composition of corrosion products recovered from patients’ periprosthetic tissue. This work specifically targets the creation of corrosion products at the metal on metal junction utilized in modular hip prosthetics. Moreover, this manuscript serves as an initial investigation into the potential interaction between implanted CoCrMo metal alloy and low amplitude electrical oscillation, similar in magnitude to those which may develop from ambient electromagnetic radiation. It is believed that introduction of such an electrical oscillation may be able to initiate electrochemical reactions between the metal and surrounding fluid, forming the precursor to secondary wear particles, without mechanically eroding the metal’s natural passivation layer. Here, we show that a low magnitude electrical oscillation (≤ 200 mV) in the megahertz frequency (106 Hz) range is capable of initiating corrosion on implanted CoCrMo without the addition of mechanical wear. Specifically, a 50 MHz, 200 mVpp sine wave generates corrosion products comprising of Cr, P, Ca, O, and C, which is consistent with previous literature on the analysis of failed hip prosthetics. These findings demonstrate that mechanical wear may not be required to initiate the production of chemically complex corrosion products.

Peri-prosthetic Fat Grafting Decreases Collagen Content, Density, and Fiber Alignment of Implant Capsules.

Background:Lower capsular contracture rates have been observed with peri-prosthetic fat grafting. We investigated the effect of fat grafting on capsular characteristics and peri-prosthetic collagen density, content, and fiber alignment.Methods:Forty miniature tissue expanders were placed on the backs of 20 rats. After four weeks, both inguinal fat pads were harvested, homogenized, and injected into peri-prosthetic tissue of the right tissue expander (fat graft) while the left served as control. The animals were killed at three (10 rats) and 12 weeks (10 rats), and full thickness peri-prosthetic samples were histologically processed for morphology (H&E) and collagen type and content (picrosirius red).Results:An 8.1% increase in adipose peri-prosthetic thickness was associated with a 10% decrease in collagen content at any time point (P = 0.004). Fat-grafted capsules displayed a 59% reduction in % total collagen when compared with controls (P < 0.001). There were no differences in capsular thickness. Fat-grafted samples were 54 times more likely to have a higher inflammation score and 69 times more likely to have a lower capsular density score than their nongrafted counterparts (P < 0.001 and P = 0.001, respectively). The extent of inflammation decreased over time in all samples (P = 0.002). Additionally, fat-grafted samples were 67 times more likely to have a lower fiber alignment score than the controls (P < 0.001).Conclusions:Enhancement of peri-prosthetic tissue with fat grafting decreases collagen content, density, and fiber alignment of implant capsules. These findings support clinical application of fat grafting in prosthetic breast surgery to potentially decrease capsular contracture.

Reproducibility of pathologic scoring systems for periprosthetic adverse local tissue reactions: A cross-sectional study

BackgroundSeveral previous studies have described broad histologic classifications of peri-prosthetic reactions that likely reflect the underlying mechanism of arthroplasty failure; however, a consensus has not yet been reached about the relative importance of individual observations. Question/PurposeThe purpose of this study was to evaluate the inter-examiner repeatability of commonly used histopathologic grading methods, and to determine the utility of assigning a more simple, global categorization in patients undergoing revision THA surgery of implants with a variety of bearing combinations. MethodsBetween March 2013 and February 2020, a total of 2131 patients underwent revision hip arthroplasty surgery at a one center, of which 12% (248 of 2131) of patients were enrolled. Two pathologists independently reviewed microscope slides of periprosthetic tissue from these patients, of which 425 slides (229 hips, 222 subjects) were reviewed by both pathologists. Separate slides were used for a priori training of the pathologists. Slides were evaluated with the Campbell Aseptic Lymphocyte-dominant Vasculitis-Associated Lesion (ALVAL) score, the Oxford ALVAL score as modified by Grammatopolous, the Fujishiro and Natu scores, and a proposed simplified pattern classification, similar to that of Krenn et al., that incorporates individual factors of these existing scoring methods and was previously shown to correspond to Magnetic Resonance Imaging findings. Inter-rater agreement was assessed using Gwet’s AC1 and AC2 coefficients and correspondence analysis was used to examine associations between individual factors of prior scoring methods with the proposed major pattern. ResultsAlmost perfect inter-rater repeatability (Gwet’s AC2 > 0.8) was found for 71% (15/21) of the individual factors, and substantial interrater agreement was found for the proposed major overall pattern (Gwet’s AC1: 0.80, 95%CI: 0.72–0.85). Correspondence analysis was able to explain 89–91% of data variability and was able to identify individual features not commonly associated with a major pattern, but discriminatory of the major pattern, such as “Lymph Cuff Thickness 0.25–0.5″ with ALVAL. ConclusionIn contrast to prior examinations, excellent interrater agreement was found that may be attributable to a priori training of raters with a test set of slides or difficulty of interpreting grading criteria. The proposed simplified major pattern classification may facilitate evaluation of histopathologic tissue samples.

Cutibacterium acnes clonal complexes display various growth rates in blood culture vials used for diagnosing orthopedic device-related infections

ObjectivesBlood culture bottles (BCBs) are commonly used for the diagnosis of infections associated with orthopedic devices. Although Cutibacterium acnes is an important pathogen in orthopedics, relatively little is known about its growth characteristics in BCBs. This prompted us to analyze the influence of bacterial genotype and clinical significance on time-to-detection (TTD) in BCBs. MethodsWe reviewed 59 cases of orthopedic device-related infections in which at least one intraoperative specimen yielded a pure C. acnes culture from anaerobic BCBs (BD Bactec Lytic/10 Anaerobic/F; Lytic-Ana) and/or solid media. A strain was considered infectant if the same genotype was present in two or more intraoperative samples. From these cases, we isolated a total of 72 unique C. acnes strains belonging to four multilocus sequence type clonal complexes (CCs): CC18, CC28, CC36 and CC53. Growth rate and TTD in Lytic-Ana BCB were studied under experimental conditions (inoculation of standard inoculum) and in clinical samples (inoculation of periprosthetic tissue samples). ResultsMedian TTD values were shorter for CC53 compared to other CCs under experimental conditions (69 vs. 103 h; p < 0.001) and from clinical specimens (70 vs. 200 h; p = 0.02). Infectant strains had a shorter median TTD compared to contaminant strains in a clinical situation, while the difference was not observed under experimental conditions. ConclusionsThe detection dynamics of C. acnes in Lytic-Ana BCBs were associated with genotype. Thus, TTD not only reflects the bacterial load in clinical samples, but may also reflect the intrinsic properties of the clonal complex of C. acnes.

Shotgun-metagenomics based prediction of antibiotic resistance and virulence determinants in Staphylococcus aureus from periprosthetic tissue on blood culture bottles

Shotgun-metagenomics may give valuable clinical information beyond the detection of potential pathogen(s). Identification of antimicrobial resistance (AMR), virulence genes and typing directly from clinical samples has been limited due to challenges arising from incomplete genome coverage. We assessed the performance of shotgun-metagenomics on positive blood culture bottles (n = 19) with periprosthetic tissue for typing and prediction of AMR and virulence profiles in Staphylococcus aureus. We used different approaches to determine if sequence data from reads provides more information than from assembled contigs. Only 0.18% of total reads was derived from human DNA. Shotgun-metagenomics results and conventional method results were consistent in detecting S. aureus in all samples. AMR and known periprosthetic joint infection virulence genes were predicted from S. aureus. Mean coverage depth, when predicting AMR genes was 209 ×. Resistance phenotypes could be explained by genes predicted in the sample in most of the cases. The choice of bioinformatic data analysis approach clearly influenced the results, i.e. read-based analysis was more accurate for pathogen identification, while contigs seemed better for AMR profiling. Our study demonstrates high genome coverage and potential for typing and prediction of AMR and virulence profiles in S. aureus from shotgun-metagenomics data.