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
Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant ( In vitro, interleukin-1 beta (IL-1β) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage.Aims
Methods
Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA. After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1β was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry.Aims
Methods
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
To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMD In vitro, OA chondrocytes were treated with ultrasound (US), US-targeted microbubble destruction (UTMD), simvastatin (SV), and UTMDAims
Methods
Periprosthetic joint infections (PJIs) and osteomyelitis are clinical challenges that are difficult to eradicate. Well-characterized large animal models necessary for testing and validating new treatment strategies for these conditions are lacking. The purpose of this study was to develop a rabbit model of chronic PJI in the distal femur. Fresh suspensions of Aims
Methods
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
Diffuse noxious inhibitory control (DNIC) works through the “pain-inhibits-pain” principle in which an additional painful (conditioned) stimulus can suppress the initial experienced pain through the descending and inhibiting pathways. Painful stimulation produced less pain inhibition in patients with knee osteoarthritis patients (KOA) than in controls, suggesting an impaired DNIC function and a loss of endogenous pain modulation. Electroacupuncture (EA) is widely used to treat acute pain associated with KOA, but the available evidence of its benefit on chronification of acute pain is scarce. This is a single-arm clinical study aims to evaluate the effect of EA on the chronification of pain associated with KOA and provide a profile of various cytokines underlying the pathogenesis of KOA. Participants are recruited through hospital-based recruitment and advertisements, diagnosis was based upon the criteria formulated by the American College of Rheumatology. Each participant was administered with EA (2 mA < current < 5 mA) at the ipsilateral EX-LE5, ST35, ST34 and SP10 for two weeks (once a day, 30 minutes per session, in 5 sessions per week). Visual Analog Scale (VAS), DNIC function, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Numerical Rating Scale (NRS), Emotional Scale (ES) and Present Pain Intensity (PPI) are evaluated before treatment and after 5 to 10 sessions of treatment. Cytokines including GRO, TNF-α, VEGF, IP-10, IL-1β, IL-17, IL-8, MCP-1 and IL-10 levels in plasma were measured using a Human Cytokine/Chemokine Magnetic Bead Panel on MAGPIX instrument before and after two weeks of treatment. A total of 39 patients with KOA were enrolled in our study (age: 63.46±9.89 years; height: 1.63±0.07 m; BMI: 22.83±2.89), all of them completed the trial. After 5 sessions of EA treatment, a significant decrease of VAS, WOMAC scores, NRS, ES and PPI was detected, but no significant difference in DNIC was observed. After two weeks' treatment, all clinical parameters (VAS, DNIC, WOMAC, NRS, ES, PPI) reduced significantly when compared with baseline; GRO, IL-17A, IL-1b, IL-8, MCP-1, TNF-a, VEGF levels in plasma reduced significantly while IL-10 and IP-10 concentrations were elevated. This study appeared to provide evidence that EA was effective in improving chronic pain associated with KOA through repairing the impaired DNIC function and down-regulation of OA detrimental cytokines. A randomized controlled prospective study with large sample size is required to clarify the effect of EA in reversing the chronification of pain in KOA.
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
