Antimicrobial peptides occur naturally in our intrinsic immune system. PLG0206 is a novel, engineered, 24-amino acid peptide which has broad-spectrum antimicrobial activity, including in biofilm and against multi-drug resistant pathogens (1,2). This is the first clinical study to evaluate the safety and tolerability of PLG0206 when administered via an irrigation solution in patients with periprosthetic joint infections (PJI) following total knee arthroplasty (TKA) during debridement, antibiotics, and implant retention (DAIR). Secondary objectives were to evaluate pharmacokinetics (PK), biomarkers and initial clinical efficacy at one year post-DAIR procedure. This prospective, multicenter, open-label, interventional study assessed two dose levels of PLG0206. Fourteen patients underwent revision for PJI after TKA. At the end of debridement, they received a single intra-articular irrigation of PLG0206 into the wound cavity lasting 15 minutes at concentrations of 3 mg/mL (n=7) or 10 mg/mL (n=7). Patients received post-operative care and intravenous/oral antimicrobial therapy as per their institutional guidelines. Patients were monitored for safety and signs of relapse or persistent infection for 12 months post study drug administration and PK and blood biomarkers were assessed.Aim
Method
Septic arthritis is a painful infection of articular joints that is typically treated by irrigation & debridement along with antibiotic therapy. There is debate amongst the medical community whether antibiotic administration should be delayed until fluid cultures have been taken to improve culture yield. However, delaying antibiotics can also have negative consequences, including joint destruction and sepsis. Therefore, the purposes of this study were to determine: 1) whether delayed antibiotic treatment affects culture yield and prognosis and 2) if the culture yield of patients treated for septic arthritis differs for hip, knee, and shoulder based on timing of antibiotic administration. A retrospective analysis was conducted on 111 patients with septic arthritis of the hip, knee, or shoulder admitted from 3/2016 to 11/2018. In patients with multiple septic joints, each joint was analyzed individually (n=122). Diagnosis was determined by the treatment of irrigation & debridement and/or a positive culture. Patients without all intervention times recorded or with periprosthetic joint infection were excluded. Demographics, laboratory tests, culture results, and intervention times were obtained through chart review. Patients were grouped based on antibiotic therapy timing: >24 hours prior to arthrocentesis (Group 1), between 24 hours and 1 hour prior (Group 2), and 1 hour prior to post-arthrocentesis (Group 3). Analysis was conducted using chi-squared tests.Aim
Method
Mechanical loosening of total hip replacement (THR) is primarily diagnosed using radiographs, which are diagnostically challenging and require review by experienced radiologists and orthopaedic surgeons. Automated tools that assist less-experienced clinicians and mitigate human error can reduce the risk of missed or delayed diagnosis. Thus the purposes of this study were to: 1) develop an automated tool to detect mechanical loosening of THR by training a deep convolutional neural network (CNN) using THR x-rays, and 2) visualize the CNN training process to interpret how it functions. A retrospective study was conducted using previously collected imaging data at a single institution with IRB approval. Twenty-three patients with cementless primary THR who underwent revision surgery due to mechanical loosening (either with a loose stem and/or a loose acetabular component) had their hip x-rays evaluated immediately prior to their revision surgery (32 “loose” x-rays). A comparison group was comprised of 23 patients who underwent primary cementless THR surgery with x-rays immediately after their primary surgery (31 “not loose” x-rays). Fig. 1 shows examples of “not loose” and “loose” THR x-ray. DenseNet201-CNN was utilized by swapping the top layer with a binary classifier using 90:10 split-validation [1]. Pre-trained CNN on ImageNet [2] and not pre-trained CNN (initial zero weights) were implemented to compare the results. Saliency maps were implemented to indicate the importance of each pixel of a given x-ray on the CNN's performance [3].INTRODUCTION
METHODS
Component position and overall limb alignment following total knee arthroplasty (TKA) have been shown to influence prosthetic survivorship and clinical outcomes. Robotic-assisted (RA) total knee arthroplasty has demonstrated improved accuracy to plan in cadaver studies compared to conventionally instrumented (manual) TKA, but less clinical evidence has been reported. The objective of this study was to compare the three-dimensional accuracy to plan of RATKA with manual TKA for overall limb alignment and component position. A non-randomized, prospective multi-center clinical study was conducted to compare RATKA and manual TKA at 4 U.S. centers between July 2016 and August 2018. Computed tomography (CT) scans obtained approximately 6 weeks post-operatively were analyzed using anatomical landmarks. Absolute deviation from surgical plans were defined as the absolute value of the difference between the CT measurements and surgeons’ operative plan for overall limb, femoral and tibial component mechanical varus/valgus alignment, tibial component posterior slope, and femoral component internal/external rotation. We tested the differences of absolute deviation from plan between manual and RATKA groups using stratified Wilcoxon tests, which controlled for study center and accounted for skewed distributions of the absolute values. Alpha was 0.05 two-sided. At the time of this abstract, data collections were completed for two centers (52 manual and 58 RATKA).Introduction
Methods
Knee arthrodesis (KA) and above knee amputation (AKA) have been used for salvage of failed total knee arthroplasty (TKA) in the setting of periprosthetic joint infection (PJI). The factors that lead to a failed fusion and progression to AKA are not well understood. The purpose of our study was to determine factors associated with failure of a staged fusion for PJI and predictive of progression to AKA. We retrospectively reviewed a single-surgeon series of failed TKA for PJI treated with two-stage KA between 2000 and 2016 with minimum 2-year follow-up. Patient demographics, comorbidities, surgical history, tissue compromise, and radiographic data were recorded. Outcomes were additional surgery, delayed union, Visual Analog Pain scale (VAS) and Western Ontario and McMaster Activity score (WOMAC). No power analysis was performed for this retrospective study. Medians are reported as data were not normally distributed.Aim
Method
Traditionally, serum white blood count (WBC), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) have been utilized as markers to evaluate septic arthritis (SA). Recently, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been identified as prognostic factors for treatment failure, mortality and morbidity in various clinical settings. To date, these markers have not been utilized for evaluating outcomes after hip and knee SA. Thus, the purpose of this study was to determine the ability of admission NLR and PLR to predict treatment failure and postoperative 90-day mortality in hip and knee SA. A retrospective study was performed using our institutional research patient database to identify 235 patients with native hip and knee septic arthritis from 2000–2018. Patient demographics, comorbidities and social factors (alcohol intake, smoking and intravenous drug use) were obtained, and NLR and PLR were calculated based on complete blood count values (absolute neutrophil, lymphocyte and platelet count) on admission. Treatment failure was defined as any reoperation or readmission within 90 days after surgery. Receiver operating curves were analyzed, and optimal thresholds for NLR and PLR were determined using Youden's test. Univariate and multivariate analyses were performed to determine if these ratios were independent predictors of treatment failure and 90-day mortality after surgery. These ratios were compared to serum WBC, CRP, and ESR.Aim
Method
Peri-operative hyperglycemia has many etiologies, including medication, impaired glucose tolerance, uncontrolled diabetes mellitus (DM), or stress, the latter of which is common in post-surgical patients. Our study aims were to investigate if post-operative day 1 (POD1) blood glucose level was associated with post-operative complications after total joint arthroplasty (TJA), including periprosthetic joint infection (PJI), and to determine a threshold for glycemic control that surgeons should strive for during a patient's hospital stay. A single-institution retrospective review was conducted on 24,857 primary TJAs performed from 2001–2015. Of these, 13,198 had a minimum one-year follow-up (mean 5.9 years). Demographics, Elixhauser comorbidities, laboratory values, complications and readmissions were collected. POD1 morning blood glucose levels were utilised and correlated with PJI, as defined by the Musculoskeletal Infection Society criteria. The mean age and body mass index of the population was 63.4 years and 30.2 kg/m2, respectively; the sample was comprised of 56.6% females and 48.4% knees. Multivariate analysis was used to determine the influence of several important covariates on complication rate. Youden's J statistic was utilised to determine an optimal blood glucose threshold. An alpha level of 0.05 was used to determine statistical significance.Introduction
Methods
Tibial and femoral component overhang in total knee arthroplasty (TKA) is a source of pain, thus is it important to understand anatomic differences between races to minimize overhang by matching the tibial and femoral shaft axis to the knee articular surface. Thus, this study compared knee morphology between Caucasian and East Asian individuals to determine the optimal placement of tibial and femoral stems. A retrospective study was conducted on a matched cohort of 50 East Asians (21F, 29M) and 50 Caucasians (21F, 29M) by age and gender. CT scans were obtained in healthy volunteers using <2mm slices. The distance from the proximal tibial diaphysis axis to the tibial plateau center was measured, and the distance from the distal femoral diaphysis axis to the center of distal femoral articular surface was measured. Tibial measurements were made using Akagi's AP axis and the widest ML diameter, and femoral measurements were based on Whiteside's line and the surgical epicondylar axis.Purpose
Methods
The direct anterior approach (DAA) for total hip arthroplasty (THA) is marketed with claims of superiority over other approaches. Femoral exposure can be technically challenging and potentially lead to early failure. We examined whether surgical approach is associated with early THA failure. A retrospective review of 478 consecutive early revision THAs within five years of primary THA at three academic centers from 2011 through 2014 was performed. Exclusion criteria resulted in a final analysis sample of 341 early failure THAs. Primary surgical approach was documented for each revision, along with time to revision, and failure etiology.Background
Methods
Sequentially annealed, highly crosslinked polyethylene (HXLPE) has been used clinically in total knee arthroplasty (TKA) for over a decade[1]. However, little is known about the reasons for HXLPE revision, its surface damage mechanisms, or its Four hundred and fifty-six revised tibial inserts in two cohorts (sequentially annealed and conventional UHMWPE control) were collected in a multicenter retrieval program between 2000 and 2016. We controlled for implantation time between the two cohorts by excluding tibial inserts with a greater implantation time than the longest term sequentially annealed retrieval (9.5 years). The mean implantation time (± standard deviation) for the sequentially annealed components was 1.9 ± 1.7 years, and for the control inserts, 3.4 ± 2.7 years (Figure 1). Reasons for HXLPE revision were assessed based on medical records, radiographs, and examinations of the retrieved components. Surface damage mechanisms were assessed using the Hood method[2]. Oxidation was measured at the bearing surface, the backside surface, the anterior and posterior faces, as well as the post (when available) using FTIR (ASTM F2102). Surface damage and oxidation analyses were available for 338 of the components. We used nonparametric statistical testing to analyze for differences in oxidation and surface damage when adjusting for polyethylene formulation as a function of implantation time.Background
Methods
During revision surgery with a well-fixed stem, a titanium sleeve can be used in conjunction with a ceramic head to achieve better stress distribution across the taper surface. Previous studies have observed that the use of a ceramic head can mitigate the extent of corrosion damage at the taper. Moreover, Thirty sleeved ceramic heads (Biolox Option: CeramTec) were collected during revision surgery as part of a multi-center retrieval program. The sleeves were used in conjunction with a zirconia-toughened alumina femoral head. The femoral heads and sleeves were implanted between 0.0 and 3.25 years (0.8±0.9, Figure 1). The implants were revised predominantly for instability (n=14), infection (n=7), and loosening (n=5). Fifty percent of the retrievals were implanted during a primary surgery, while 50% had a history of a prior revision surgery. Fretting corrosion was scored using a previously described 4-point, semi-quantitative scoring system proposed by Higgs [2].Introduction
Materials and Methods
Hospital systems have recently instituted early systemic sepsis recognition systems, where vital signs and laboratory findings are monitored and automatically alert providers to potential sepsis. Although there are very few reports evaluating the use of sepsis alert systems outside of the emergency room or intensive care unit, many hospital systems have made the decision to apply the sepsis alarm protocols to all inpatients. The purpose of this study was to evaluate if an alarm system using systemic inflammatory response syndrome (SIRS) criteria is a valuable tool to predict systemic sepsis in the immediate postoperative period (POD#0–4) after total joint arthroplasty (TJA). 10,791 primary and revision TJA patients at one institution, from 2010–2014, were retrospectively reviewed for positive SIRS criteria on each hospital day from the date of surgery to postoperative day four (POD#4). SIRS criteria included temperature > 38°C or < 36°C, heart rate > 90 beats per minute, respiratory rate > 20 breaths per minute, and white blood cell (WBC) > 12,000/mm3 or < 4,000/mm3. Additionally, hospital coding data was cross-referenced to identify patients who were diagnosed with systemic sepsis within 10 days after having a TJA.Aim
Method
Different perioperative strategies have been implemented to reduce the devastating burden of infection following arthroplasty. The use of iodophor-impregnated adhesive incise drapes is one such strategy. Despite its wide adoption, there is little proof that this practice leads to a reduction of bacterial colonization. The aim of this randomized, prospective study was to evaluate the efficacy of iodophor-impregnated adhesive drapes for reducing bacterial count at the incision site. A total of 96 patients undergoing open joint preservation procedure of the hip were enrolled in this prospective, randomized clinical trial of iodophor-impregnated adhesive drapesAim
Method
Perioperative hyperglycemia has many etiologies including medication, impaired glucose tolerance, uncontrolled diabetes mellitus (DM), or stress, the latter of which is common to post-surgical patients. This acute hyperglycemia may impair the ability of the host to combat infection.1 Our study aims to investigate if post-operative day 1 (POD1) blood glucose level is associated with complications, including periprosthetic joint infection (PJI), after total joint arthroplasty (TJA) and to determine a threshold for glycemic control that surgeons should strive for during a patient's hospital stay. A single-institution retrospective review was conducted on 24,857 primary TJAs performed from 2001–2015. Demographics, Elixhauser comorbidities, laboratory values, complications and readmissions were collected. POD1 morning blood glucose levels were utilized and correlated with PJI, as defined by the Musculoskeletal Infection Society criteria. The Wald test was used to determine the influence of covariates on complication rate. An alpha level of 0.05 was used to determine statistical significance.Aim
Method
Previous studies of long-term CoCr alloy femoral components for TKA have identified 3rd body abrasive wear and inflammatory cell induced corrosion (ICIC). The extent of femoral condyle surface damage in contemporary CoCr femoral components is currently unclear. The purpose of this study was to investigate the prevalence and morphology of damage (3rd body scratches and ICIC) at the bearing surface in retrieved TKA femoral components from contemporary designs. 308 CoCr femoral TKA components were collected as part of an ongoing, multi-institutional orthopedic implant retrieval program. The collection included contemporary designs from Stryker (Triathlon n=48, NRG n=10, Scorpio n=31), Depuy Synthes (PFC n=27) and Zimmer (NexGen n=140, Persona n=1) and Biomet (Vanguard n=51). Hinged knee designs and unicondylar knee designs were excluded. Components were split into groups based on implantation time: short-term (1–3y, n=134), intermediate-term (3–5y, n=73) and long-term (6–15y, n=101). Each grouping was mainly revised for instability, infection and loosening. Third-body abrasive wear of CoCr was evaluated using a semi-quantitative scoring method similar to the Hood method (Figure 1). A score of 1 had minimal damage and a score of 4 corresponded to damage covering more than 50% of the evaluated area. ICIC damage was reported as location of affected area. A white light interferometer (Zygo New View 5000) was also used to analyze the topography of severe damage of the bearing surface. For this analysis, three representative components from each cohort were selected and analyzed in three locations on the apex of the bearing surface. We analyzed the following roughness parameters: Ra, Rsk, and Rku.Introduction
Methods
Highly crosslinked polyethylene (HXLPE) was clinically introduced approximately a decade and a half ago to reduce polyethylene wear rates and subsequent osteolysis. Clinical and radiographic studies have repeatedly shown increased wear resistance, however concerns of rim oxidation and fatigue fracture remain. Although short to intermediate term retrieval studies of these materials are available, the long-term behavior of these materials remains unclear. Between 2000 and 2015, 115 1st generation HXLPE acetabular liners implanted for 5 or more years were collected and analyzed as part of an ongoing, multi-institutional orthopaedic implant retrieval program. There were two material cohorts based on thermal processing (annealed (n=45) and remelted (n=70)). Each cohort was stratified into two more cohorts based on implantation time (5 – 10 years and >10 years). For annealed components, the intermediate-term liners (n=30) were implanted on average (±SD) for 7.3 ± 1.7 years while the long-term liners (n=15) were implanted for 11.3 ± 1.8 years. For remelted components, the intermediate-term liners (n=59) were implanted on average (±SD) for 7.2 ± 1.3 years while the long-term liners (n=11) were implanted for 11.3 ± 1.2 years. For each cohort, the predominant revision reasons were loosening, instability, and infection (Figure 1). Short-term liners (in-vivo <5ys) from previous studies were analyzed using the same protocol for use as a reference. For oxidation analysis, thin slices (∼200 μm) were taken from the superior/inferior axis and subsequently boiled in heptane for 6 hours to remove absorbed lipids that may interfere with the oxidation analysis. 3mm line profiles (in 100μm increments) were taken perpendicular to the surface at each region of interest. Oxidation indices were calculated according to ASTM 2102. Penetration was measured directly using a calibrated micrometer (accuracy=0.001mm).Introduction
Methods
Previous studies of retrieved CoCr alloy femoral heads have identified imprinting of the stem taper surface features onto the interior head bore, leading researchers to hypothesize that stem taper microgrooves may influence taper corrosion. However, little is known about the role of stem taper surface morphology on the magnitude of in vivo corrosion damage. We designed a matched cohort retrieval study to examine this issue. From a multi-institutional retrieval collection of over 3,000 THAs, 120 femoral head-stem pairs were analyzed for evidence of fretting and corrosion using a visual scoring technique based on the severity and extent of fretting and corrosion damage observed at the taper. A matched cohort design was used in which 60 CoCr head-stem pairs with a smooth stem taper were matched with 60 CoCr head-stem pairs having a micro-grooved surface, based on implantation time, flexural rigidity, apparent length of taper engagement, and head size. This study was adequately powered to detect a difference of 0.5 in corrosion scores between the two cohorts, with a power of 82% and 95% confidence. Both cohorts included CoCr and Ti-6-4 alloy femoral stems. A high precision roundness machine (Talyrond 585, Taylor Hobson, UK) was used to measure surface morphology and categorize the stem tapers into smooth vs. micro-grooved categories. Fretting and corrosion damage at the head/neck junction was characterized using a modified semi-quantitative adapted from the Goldberg method by three independent observers. This method separated corrosion damage into four visually determined categories: minimal, mild, moderate and severe damage.Introduction
Methods
It is strongly recommended that tissue and synovial fluid culture samples be obtained during reimplantation performed as part of a two-stage exchange arthroplasty. The incidence of positive cultures during reimplantation and the influence of positive cultures on subsequent outcome are unknown. This aim of this study was to determine the incidence of positive cultures during reimplantation and to investigate the association between positive cultures at reimplantation and the subsequent outcome A retrospective review was conducted on 267 patients that met the Musculoskeletal Infection Society (MSIS) criteria for PJI that completed both stages of two-stage exchange arthroplasty (Table 1). Intraoperative culture results from tissue and/or synovial fluid were obtained. Cultures were positive in 33 cases (12.4%) undergoing reimplantation surgery (Figure 1). Treatment failure was assessed based on the Delphi consensus definition. Logistic regression analysis was performed to assess the predictors of positive culture and risk factors for failure of two-stage exchange arthroplasty. Treatment failure was 45.5% for those with a positive intraoperative culture and 20.9% in those with negative cultures at the time of reimplantation. When controlling for organism virulence, comorbidities, and other confounding factors, treatment failure was higher (odds ratio [OR]: 3.3; 95% confidence interval [CI]: 1.3–4.5) and occurred at an earlier time point (hazard ratio: 2.5; 95% CI: 1.3–4.5) in patients with a positive reimplantation culture. The treatment failure rate was not different between cases with two or more positive cultures (36.4%) and one positive culture (42.8%). Positive intraoperative cultures during reimplantation, regardless of the number of positive samples were independently associated with two times the risk of subsequent infection and earlier treatment failure. Surgeons should be aware that a positive culture at the time of reimplantation independently increases the risk of subsequent failure and needs to be taken seriously. Given the significance of these findings, future studies are needed to evaluate the optimal management of positive cultures during reimplantation surgery.
Perioperative antibiotic prophylaxis remains one of the most important strategies for prevention of periprosthetic joint infection (PJI) with current guideline recommending a first or second generation cephalosporin. Penicillin (PCN) allergy is often reported by patients, which often results in avoidance of administration of cephalosporins due to fear of cross-reactivity. Alternative medications, such as vancomyin, are often used despite reduced antimicrobial coverage. The purpose of this study was to determine if PCN allergic patients who received vancomycin alone prior to elective primary total joint arthroplasty were at increased risk of developing a subsequent PJI. A retrospective review of 7,602 primary total joint arthroplasties (TJAs) performed between 2005 and 2013 in two institutions were identified using a prospective institutional database. Patient reported PCN or cephalosporin allergy was electronically queried from the anesthesia note. Patients who recieved multiple prophylactic antibiotics, or had unavailable perioperative antibiotic information, or those who received medication other than cefazolin and vancomycin were excluded. PJI was determined using a cross-match with an institutional PJI database constructed from International Classification of Diseases (ICD)-9 codes. Logistic regression analysis was then performed to evaluate the risk of subsequent PJI. The rate of PJI was 1.4% (32/2296) in patients with a reported PCN allergy that received vancomycin alone versus 1.1% (59/5306) in non-PCN allergic patients that received cefazolin alone. The multivariate analysis, with the given sample size, did not detect a statistically significant increased risk of PJI when vancomycin was administered alone (adjusted odds ratio: 1.23, 95% CI 0.6–3.1, p=0.35). While there was no significant differences in the organism profile between PJIs in both groups, the rate of PJI caused by resistant organisms was higher in patients who received vancomycin alone (11.9%, 7/59) compared to those who received cefazolin (3.1%, 1/32). While administration of perioperative prophylactic vancomycin alone during elective primary arthroplasty does not seem to result in a higher rate of subsequent PJI, patients who received vancomycin alone and developed a PJI were more likely to develop an infection with an antibiotic resistant organism. Future studies are needed to determine the most appropriate prophylactic antibiotic for patients who undergo elective arthroplasty and report PCN allergy.
Considerable efforts have been invested into identifying risk factors for periprosthetic joint infection (PJI) after total joint arthroplasty (TJA). Preoperative identification of risk factors for developing PJI is imperative for medical optimization and targeted prophylaxis. The purpose of this study was to create a preoperative risk calculator for PJI by assessing a patient's individual risks for developing PJI with resistant organisms and S.aureus. A retrospective review of 27117 patients (43253 TJAs) from 1999 to 2014, including 1035 PJIs, was performed. A total of 41 risk factors including demographics, comorbidities (using the Elixhauser and Charlson Index), and the number of previous TJAs, were evaluated. Multivariate analysis was performed; coefficients of the models were scaled to produce useful integer scoring. Predictive model strength was assessed employing area under the curve (AUC) analysis. Among the 41 assessed variables, the following were significant risk factors in descending order of significance: prior surgeries (p<0.0001), drug abuse (p=0.0003), revision surgery (p<0.0001), human immunodeficiency virus (p=0.0004), coagulopathy (p<0.0001), renal disease (p<0.0001), congestive heart-failure (p<0.0001), psychoses (p=0.0024), rheumatological disease (p<0.0001), knee involvement (p<0.0001), diabetes (p<0.0001), anemia (p<0.0001), males (p<0.0001), liver disease (p=0.0093), smoking (p=0.0268), and high BMI (p<0.0001). Furthermore, presence of heart-valve disease (p=0.0409), metastatic disease (p=0.0006), and pulmonary disease (p=0.0042) increased the resistant organism PJIs. Patients with metastatic disease were also more likely to be infected with S. aureus (p=0.0002). AUCs were 0.83 for any PJI, 0.86 for resistant PJI, and 0.84 for S.aureus PJI models. This large-scale single-institutional study has determined various risk factors for PJI. Some factors are modifiable and need to be addressed before elective arthroplasty. It is imperative that surgeons are aware of these risk factors and implement all possible preventative measures, including targeted prophylaxis, in patients with high-risk of PJI. Continued efforts are needed to find novel and effective solutions to minimize the burden PJI.
