Abdel, Matthew P.

Abstract Background Periprosthetic joint infection (PJI), a devastating complication of total joint replacement, is of incompletely understood pathogenesis and may sometimes be challenging to clinically distinguish from other causes of arthroplasty failure. Methods We characterized human gene expression in 93 specimens derived from surfaces of resected arthroplasties, comparing transcriptomes of subjects with infection- versus non-infection-associated arthroplasty failure. Results Differential gene expression analysis confirmed the association of 28 previously investigated biomarkers with PJI- bactericidal/permeability increasing protein (BPI), cathelicidin antimicrobial peptide (CAMP), chemokines CCL3, CCL4, and CXCL2, colony stimulating factor 2 receptor (CSF2RB), colony stimulating factor 3 (CSF3), alpha-defensin (DEFA4), receptor CD64B, intercellular adhesion molecule 1 (ICAM1), IFNG, IL13RA2, IL17D, IL1A, IL1B, IL1RN, IL2RA, IL2RG, IL5RA, IL6, IL8, lipopolysaccharide binding protein (LBP), lipocalin (LCN2), lactate dehydrogenase C (LDHC), lactotransferrin (LTF), matrix metallopeptidase 3 (MMP3), peptidase inhibitor 3 (PI3), and vascular endothelial growth factor A (VEGFA), as well as identified three novel molecules with diagnostic potential for detection of PJI- chemokine CCL20, coagulation factor VII (F7), B cell receptor FCRL4. Comparative analysis of infections caused by staphylococcal versus non-staphylococcal and Staphylococcus aureus versus Staphylococcus epidermidis showed significant elevated expression of IL13, IL17D, and metalloprotease protein MMP3 in staphylocococcal infections, and increased expression of IL1B, IL8, and platelet factor PF4V1 in S. aureus infections. Pathway analysis of over-presented genes suggested activation of host immune response and cellular maintenance and repair functions in response to invasion of infectious agents. Conclusion Our study provides new potential targets for diagnosis of PJI and targets for differentiation of PJI-associated infectious agents. Disclosures Matthew P. Abdel, MD, Dr. Abdel receives royalties from Stryker on certain hip and knee products, and is a paid consultant for Stryker. (Consultant) Robin Patel, MD, Accelerate Diagnostics (Grant/Research Support)CD Diagnostics (Grant/Research Support)Contrafect (Grant/Research Support)Curetis (Consultant)GenMark Diagnostics (Consultant)Heraeus Medical (Consultant)Hutchison Biofilm Medical Solutions (Grant/Research Support)Merck (Grant/Research Support)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued.)Selux Dx (Consultant)Shionogi (Grant/Research Support)Specific Technologies (Consultant)

Background: Extended trochanteric osteotomies (ETOs) provide wide femoral and acetabular exposure, give direct access to the femoral medullary canal, and facilitate implant removal and new implant placement during selected revision total hip arthroplasties (THAs). Previous studies are limited by modest patient numbers and limited length of follow-up. The goals of the current study were to assess the union rate, complications, and outcomes of contemporary ETOs performed during revision THAs. Methods: From 2003 to 2013, 612 ETOs were performed during revision THAs at 1 institution using 2 techniques: Paprosky (laterally based osteotomy; n = 367) and Wagner (anteriorly based osteotomy; n = 245). The indications for the revision procedures were aseptic loosening (65%), periprosthetic joint infection (18%), periprosthetic fracture (6%), femoral implant fracture (5%), and other (6%). The mean patient age was 69 years, and 57% of the patients were male. The mean number of previous THAs was 1.6. The median duration of follow-up was 5 years (range, 2 to 13 years). Results: The mean Harris hip scores increased from 57 preoperatively to 77 at the latest follow-up (p < 0.001). Radiographic and clinical union was achieved in 98% of the patients at a mean of 6 months (range, 1 to 24 months). The mean migration of the proximal trochanteric osteotomy fragment prior to union was 3 mm (range, 0 to 29 mm). ETO fragment migration of >1 cm occurred in 7% (37) of the 501 hips that had radiographic analysis. Nine hips (2%) had nonunion of the ETO. Intraoperative fracture of the ETO diaphyseal fragment occurred in 22 hips (4%), postoperative fracture of the ETO diaphyseal fragment occurred in 3 hips (0.5%), and postoperative fracture of the greater trochanter occurred in 41 hips (7%). Survivorship at 10 years free of revision for aseptic femoral loosening, free of femoral or acetabular component removal or revision for any reason, and free of reoperation for any reason was 97%, 91%, and 82%, respectively. Conclusions: This large series of ETOs shows that the union rate is high and clinically important trochanteric migration is infrequent. The most common complications are fracture of the osteotomy fragment intraoperatively or postoperatively. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

(1) Background: Arthrofibrosis is a common cause of patient debility and dissatisfaction after total knee arthroplasty (TKA). The diversity of molecular pathways involved in arthrofibrosis disease progression suggest that effective treatments for arthrofibrosis may require a multimodal approach to counter the complex cellular mechanisms that direct disease pathogenesis. In this study, we leveraged RNA-seq data to define genes that are suppressed in arthrofibrosis patients and identified adiponectin (ADIPOQ) as a potential candidate. We hypothesized that signaling pathways activated by ADIPOQ and the cognate receptors ADIPOR1 and ADIPOR2 may prevent fibrosis-related events that contribute to arthrofibrosis. (2) Methods: Therefore, ADIPOR1 and ADIPOR2 were analyzed in a TGFβ1 inducible cell model for human myofibroblastogenesis by both loss- and gain-of-function experiments. (3) Results: Treatment with AdipoRon, which is a small molecule agonist of ADIPOR1 and ADIPOR2, decreased expression of collagens (COL1A1, COL3A1, and COL6A1) and the myofibroblast marker smooth muscle α-actin (ACTA2) at both mRNA and protein levels in basal and TGFβ1-induced cells. (4) Conclusions: Thus, ADIPOR1 and ADIPOR2 represent potential drug targets that may attenuate the pathogenesis of arthrofibrosis by suppressing TGFβ-dependent induction of myofibroblasts. These findings also suggest that AdipoRon therapy may reduce the development of arthrofibrosis by mediating anti-fibrotic effects in joint capsular tissues.

Background: The purpose of this multicenter, randomized trial was to determine the optimal dosing regimen of tranexamic acid (TXA) to minimize perioperative blood loss in revision total hip arthroplasty. Methods: Six centers prospectively randomized 175 patients to 1 of 4 regimens: (1) 1-g intravenous (IV) TXA prior to incision (the single-dose IV group), (2) 1-g IV TXA prior to incision followed by 1-g IV TXA after arthrotomy wound closure (the double-dose IV group), (3) a combination of 1-g IV TXA prior to incision and 1-g intraoperative topical TXA (the combined IV and topical group), or (4) 3 doses totaling 1,950-mg oral TXA (the multidose oral group). Randomization was based on revision subgroups to ensure equivalent group distribution. An a priori power analysis (α = 0.05; β = 0.80) determined that 40 patients per group were required to identify a >1-g/dL difference in postoperative hemoglobin reduction between groups. Per-protocol analysis involved an analysis of variance, Fisher exact tests, and two 1-sided t tests for equivalence. Demographic and surgical variables were equivalent between groups. Results: No significant differences were found between TXA regimens when evaluating reduction in hemoglobin (3.4 g/dL for the single-dose IV group, 3.6 g/dL for the double-dose IV group, 3.5 g/dL for the combined IV and topical group, and 3.4 g/dL for the multidose oral group; p = 0.95), calculated blood loss (p = 0.90), or transfusion rates (14% for the single-dose IV group, 18% for the double-dose IV group, 17% for the combined group, and 17% for the multidose oral group; p = 0.96). Equivalence testing revealed that all possible pairings were statistically equivalent, assuming a >1-g/dL difference in hemoglobin reduction as clinically relevant. There was 1 venous thromboembolism, with no differences found between groups (p = 1.00). Conclusions: All 4 TXA groups tested had equivalent blood-sparing properties in the setting of revision total hip arthroplasty, with a single venous thromboembolism reported in this high-risk population. Based on the equivalence between groups, surgeons should utilize whichever of the 4 investigated regimens is best suited for their practice and hospital setting. Given the transfusion rate in revision total hip arthroplasty despite TXA utilization, further work is required in this area. Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Background: Treatment of severe patellar bone loss during revision total knee arthroplasty (TKA) is difficult. Patellar bone-grafting is a simple procedure that can improve patient outcomes following revision TKA. Description: The patient is prepared and draped in the usual sterile fashion. The previous longitudinal knee incision is utilized for exposure. Scar tissue is excised from the medial gutter. However, tissue in the lateral gutter is largely maintained. An assessment of the surrounding quadriceps and patellar scar tissue ensues. This tissue can be utilized to create an envelope for holding the bone graft in place. If insufficient tissue is present, fascia from the iliotibial band or vastus medialis, allograft fascia, or synthetics can be used. A careful assessment of component fixation and rotation is critical to the success of patellar bone-grafting. Component revision for aseptic loosening or malrotation should be performed in the usual fashion. During component revision, it is recommended to preserve any additional bone as autograft for the patellar bone-grafting procedure. Common sites of autograft harvest include the femoral box cut and proximal tibial resection. The patella is then addressed by carefully removing the previous implant to avoid additional bone loss. This step is performed with a combination of an oscillating saw, osteotomes, and high-speed burr. The retropatellar bone is then prepared by debriding excess soft tissue, cysts, or cement. A high-speed burr is then utilized to produce a punctate bleeding surface for bone-graft incorporation. The harvested tissue is closed around the perimeter of the patella with use of interrupted nonabsorbable sutures, leaving a window to pack in the bone graft. The bone graft (allograft and autograft) is morselized and place through the window. The optimal patellar thickness is variable. After packing the bone graft through the soft-tissue window, the thickness is measured with a caliper. It is recommended to acquire a thickness of >20 mm because bone-graft resorption and remodeling occur with knee range of motion. The remaining soft-tissue window is closed with use of nonabsorbable sutures. The knee is cycled through a range of motion to ensure optimal patellofemoral tracking. If necessary, a lateral release or medial soft-tissue advancement can be performed to ensure patellofemoral tracking is adequate. Finally, the wound is irrigated and closed in layers. Alternatives: Nonsurgical: Surgical: Gull-wing osteotomy Patellar resurfacing with biconvex patella Bulk allograft reconstruction Partial or complete patellectomy Patelloplasty Interpositional arthroplasty Tantalum metal-backed reconstruction Rationale: There is a myriad of surgical options for severe patellar bone loss following TKA. Patellar bone-grafting is simple, reproducible, and relatively cost-effective 1,2 , and avoids the need for the amount of bone for reconstruction that may be required for metal-backed or biconvex patellar implants 3,4 . The procedure allows for the restoration of the quadriceps lever arm, which may not be restored with other techniques, such as gull-wing osteotomy or patellectomy 5 . Patellar bone-grafting avoids the cost and risks of disease transmission associated with allograft reconstruction 6 . Finally, the procedure provides excellent long-term survivorship and patient-reported outcomes. Expected Outcomes: Following this procedure, patients should experience a reduction in knee pain and improved patient-reported outcomes 2,6 , with a prior study showing that the percentage of patients reporting anterior knee pain decreased from 51% to 27% following patellar bone-grafting. Patients also demonstrated an improvement in knee range of motion, with a mean increase in knee flexion of 7 o and knee extension of 2 o1 . Complications related to this procedure are minimal. Bone stock restoration can be utilized for patellar resurfacing in the future 1 . Radiographically, patellar bone resorption, loss of patellar height, and patellar remodeling do occur; however, despite these radiographic changes, Knee Society scores increased from 50 to 85 at the time of the latest follow-up. Important Tips:

Background: The cementation of a new liner into a well-fixed acetabular component is common during revision total hip arthroplasty (THA) for many indications, but most commonly for lack of a modern, compatible, highly cross-linked polyethylene (HXLPE) liner. However, little is known about the intermediate-term to long-term durability of this strategy. The purpose of this study was to evaluate the implant survivorship, risk of complications, clinical outcomes, and radiographic results of cementing a new HXLPE liner into a well-fixed acetabular component. Methods: We retrospectively identified 323 revision THAs in which a nonconstrained HXLPE liner was cemented into a well-fixed acetabular component. The mean age at the time of the revision THA was 63 years, and 50% of patients were female. The most common indications for revision THA were polyethylene wear and osteolysis (48%), aseptic femoral loosening (35%), and hip instability (8%). The mean follow-up was 9 years. Results: Polyethylene liner failure occurred in 11 cases (3%). In all cases, the cemented liner dissociated from the acetabular component. At 10 years, the survivorship free from any revision was 80% (95% confidence interval [CI], 75% to 84%) and the survivorship free from any reoperation was 77% (95% CI, 72% to 82%). The most common reason for re-revision was dislocation (45% of reoperations). A dislocation occurred in 17% of cases. Hips that underwent revision for instability were significantly more likely to dislocate compared with hips that underwent revision for liner wear (hazard ratio [HR], 2.3 [95% CI, 1.2 to 4.5]; p = 0.02). Elevated rim or face-changing liners were significantly more likely to dissociate than flat liners (HR, 9.0 [95% CI, 1.2 to 70.6]; p = 0.04). Conclusions: Cementation of a nonconstrained HXLPE liner into a well-fixed acetabular component during revision THA provided durable fixation with only a small number of failures at the cement interface (3%). Instability after this procedure remains a concern, but this is multifactorial in nature. These data support the continued use of this technique, when necessary, during revision THA. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Background: Spinal anesthesia provides several benefits for patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA), but historically comes at the cost of slow and unpredictable return of lower-extremity motor function related to the use of long-acting local anesthetics. In this prospective, double-blinded, randomized clinical trial we sought to determine if an alternative local anesthetic, mepivacaine, would allow more consistent return of motor function compared with low-dose bupivacaine spinal anesthesia during primary THA and TKA. Methods: This trial was conducted at a single academic institution. Prior to trial initiation an internal pilot study determined that 154 patients were required to achieve 80% power. Patients were randomized in a 1:1 fashion with use of advanced computerized stratification based on procedure, age group, sex, and body mass index. Following the surgical procedure, motor function was assessed every 15 minutes in the nonoperative lower extremity according to the Bromage scale and discontinued once Bromage 0 was achieved (spontaneous movement at hip, knee, and ankle). Results: Return of lower-extremity function was more predictable in patients who received mepivacaine than in those who received low-dose bupivacaine. Among patients who received mepivacaine, 1% achieved motor function return beyond 5 hours compared with 11% of patients who received bupivacaine (p = 0.013). The mean time to return of lower-extremity motor function was 26 minutes quicker in patients who received mepivacaine (185 minutes; 95% confidence interval, 174 to 196 minutes) compared with low-dose bupivacaine (210 minutes; 95% confidence interval, 193 to 228 minutes) (p = 0.016). There were no significant differences in safety outcomes including pain scores, time to participation in physical therapy, incidence of orthostatic hypotension, urinary retention, or transient neurologic symptoms in patients receiving mepivacaine compared with low-dose bupivacaine. Conclusions: In patients undergoing primary THA and TKA, spinal anesthesia with mepivacaine allowed more consistent return of lower-extremity motor function compared with low-dose bupivacaine, without a concomitant increase in complications potentially associated with spinal anesthetics. This is particularly of value in an era of short-stay and outpatient surgical procedures. Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Background: Total knee arthroplasties (TKAs) with cementless fixation have been studied in multiple series with varying success. The aim of this study was to prepare a systematic review of the literature to evaluate clinical outcomes and revtpdelision rates of patients undergoing contemporary cementless TKA. Methods: A search of PubMed and MEDLINE was conducted for English-language articles published between 2005 and 2018 to identify studies examining survivorship and clinical outcomes of cementless TKAs. Studies that reported clinical and/or radiographic outcomes were included. Data collected included the number of TKAs, implant utilized, primary diagnosis, mean age and follow-up, implant survivorship, complications, revisions, and clinical outcome scores. All hybrid constructs and revision TKAs were excluded. Poisson regression analysis was used to determine the revision incidence rates per 1,000 person-years. Results: Forty-three studies with 10,447 TKAs met inclusion criteria, of which 8,187 were primary cementless TKAs. The mean follow-up was 7 years. The revision incidence per 1,000 person-years was 4.8 for all cementless designs. The complication rate for all cementless TKAs was 6%, with deep venous thrombosis being the most common complication. The mean postoperative Knee Society Score and Functional Score were 92 and 83, respectively. Conclusions: While newer-generation cementless designs have shown improved survivorship and clinical outcomes compared with earlier-generation cementless designs, the literature for cementless designs remains limited when compared with cemented designs. Further studies are needed to determine if cementless TKA can achieve the same benefits that have been realized with cementless total hip arthroplasty. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Abstract Background Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis. Methods Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively. Results Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group. Conclusions Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.