Abdel, Matthew P.

AbstractArthrofibrosis, which causes joint motion restrictions, is a common complication following total knee arthroplasty (TKA). Key features associated with arthrofibrosis include myofibroblast activation, knee stiffness, and excessive scar tissue formation. We previously demonstrated that adiponectin levels are suppressed within the knee tissues of patients affected by arthrofibrosis and showed that AdipoRon, an adiponectin receptor agonist, exhibited anti‐fibrotic properties in human mesenchymal stem cells. In this study, the therapeutic potential of AdipoRon was evaluated on TGFβ1‐mediated myofibroblast differentiation of primary human knee fibroblasts and in a mouse model of knee stiffness. Picrosirius red staining revealed that AdipoRon reduced TGFβ1‐induced collagen deposition in primary knee fibroblasts derived from patients undergoing primary TKA and revision TKA for arthrofibrosis. AdipoRon also reduced mRNA and protein levels of ACTA2, a key myofibroblast marker. RNA‐seq analysis corroborated the anti‐myofibrogenic effects of AdipoRon. In our knee stiffness mouse model, 6 weeks of knee immobilization, to induce a knee contracture, in conjunction with daily vehicle (DMSO) or AdipoRon (1, 5, and 25 mg/kg) via intraperitoneal injections were well tolerated based on animal behavior and weight measurements. Biomechanical testing demonstrated that passive extension angles (PEAs) of experimental knees were similar between vehicle and AdipoRon treatment groups in mice evaluated immediately following immobilization. Interestingly, relative to vehicle‐treated mice, 5 mg/kg AdipoRon therapy improved the PEA of the experimental knees in mice that underwent 4 weeks of knee remobilization following the immobilization and therapy. Together, these studies revealed that AdipoRon may be an effective therapeutic modality for arthrofibrosis.

Abstract Background Periprosthetic joint infection (PJI) is associated with significant morbidity. Management includes surgery and prolonged antibiotic treatment. Few studies have evaluated rates of acquired antimicrobial resistance in bacteria causing PJI. The aim of this study was to describe antimicrobial resistance profiles of bacteria causing PJI and to assess whether there was any apparent association between acquired resistance and clinical outcome. Methods Patients at Mayo Clinic with first episodes of knee or hip PJI whose implants underwent sonication between January 2012 and December 2021 were studied. Sonicate fluid cultures from cement spacers or cultures yielding more than one microorganism were excluded. PJI was defined according to IDSA guidelines. Multidrug resistance was defined as non-susceptibility to at least one agent in three or more antimicrobial classes. Outcomes of PJI recurrence, need for further surgery with negative cultures or cultures yielding a new microorganism and amputation were assessed, within one year. Analysis was performed using SAS software version 9.4 (SAS Inc). Results 256 PJI episodes were evaluated, 55% from knees and 45% from hips. Median patient age was 66 years, 52% were men. Resistance profiles are shown in the table. The most frequent microorganisms isolated were S. epidermidis (n=82) and S. aureus (n=50), of which 68% and 30%, respectively, were methicillin resistant. Streptococci, Enterococci, Enterobacterales, and P. aeruginosa were found in 34,16, 8 and 3 cases; none were multidrug-resistant. No differences in PJI recurrence within one year were found in subjects with methicillin-resistant compared to methicillin-susceptible staphylococci (S. aureus, 50% versus 50%, respectively, p, 0.44; S. epidermidis, none), need for further surgery with negative cultures (S. aureus, 20% versus 80%, p, 0.72; S. epidermidis, 80% versus 20%, p, 0.47) or with cultures yielding a new microorganism (S. aureus, none; S. epidermidis, 67% versus 33%, p, 0.96), or amputation (none in any subject with staphylococcal PJI). Conclusion Acquired antimicrobial resistance in PJI was most common in S. epidermidis with methicillin resistance found in 68% and multidrug resistance in 28%. Disclosures Matthew P Abdel, MD, OsteoRemedies: Royalties|Springer: Publishing royalties|Stryker: Royalties reltated to hip and knee implants Robin Patel, MD, Abbott Laboratories: Advisor/Consultant|Adaptive Phage Therapeutics: Grant/Research Support|Adaptive Phage Therapeutics: Mayo Clinic has a royalty-bearing know-how agreement and equity in Adaptive Phage Therapeutics.|BIOFIRE: Grant/Research Support|CARB-X: Advisor/Consultant|ContraFect: Grant/Research Support|Day Zero Diagnostics: Advisor/Consultant|HealthTrackRx: Advisor/Consultant|Mammoth Biosciences: Advisor/Consultant|Netflix: Advisor/Consultant|Oxford Nanopore Technologies: Advisor/Consultant|PhAST: Advisor/Consultant|See details: Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic|See details: continued, patent on an anti-biofilm substance issued|TenNor Therapeutics Limited: Grant/Research Support|Torus Biosystems: Advisor/Consultant|Trellis Bioscience, Inc.: Advisor/Consultant

AbstractBackground and ObjectivesRecent studies have reported acceptable outcomes after arthrodesis takedown and conversion to total hip arthroplasty (THA); however, there are no reports on outcomes after oncologic resection, which are inherently complex and may portend poorer outcomes. The purpose of this study was to examine the surgical and functional outcomes of patients who underwent prior hemipelvectomy for tumor resection and were later converted to THA.MethodsAll patients who had prior iliofemoral arthrodesis after oncologic resection that were later converted to THA at a single institution were examined. Charts were reviewed for demographic information, operative information, functional outcomes, and complications/reoperations.ResultsAll three patients in this study were males who underwent internal hemipelvectomies for chondrosarcoma. Patients were converted to THA at a mean of 26 years after arthrodesis. Mean follow‐up after conversion to THA was 7.4 years. During this follow‐up period, two of the three patients required revision surgery. At last follow‐up, the mean Harris Hip Score was 81 and the mean Mayo Hip Score was 67, and all patients were ambulatory without significant pain.ConclusionsOverall, patients who undergo iliofemoral arthrodesis after oncologic hemipelvectomy and are later converted to THA can expect to have a reasonable outcome, despite a high rate of complications and revision surgery.

Abstract Solutions for bone and joint infection (BJI) are needed where conventional treatments are inadequate. Bacteriophages (phages) are naturally occurring viruses that infect bacteria and have been harnessed for refractory bone and joint infections (BJI) in many case reports. Here we examine the safety and efficacy of English-language published cases of BJI since 2010 with phage therapy. From 33 reported cases of BJI treated with phage therapy, 29 (87%) achieved microbiological or clinical success, 2 (5.9%) relapsed with the same organisms, and 2 (5.9%) with a different organism. Of these 4 relapses, all but 1 had eventual clinical resolution with additional surgery or phage treatments. Eight out of 33 cases (24%) reported mild, transient adverse events with no serious events reported. Further work is needed to understand the true efficacy of phages and the role of phages in BJI. Opportunities lay ahead for thoughtfully designed clinical trials adapted to individualized therapies.

Background: As the number of primary total hip arthroplasty procedures performed each year continues to rise, so too do the number of complications, including periprosthetic femoral fracture 1–9 . Vancouver B2 and B3 periprosthetic femoral fractures are difficult to treat because they require the surgeon to simultaneously manage a femoral fracture and gain new implant fixation. Fluted tapered stems have advanced the treatment of periprosthetic femoral fractures by providing immediate axial and rotational implant fixation distal to the fracture 10–18 . Modular fluted tapered stems provide the added practical advantage of allowing length and anteversion adjustment after implantation of the distal fixation portion of the stem. Description: In this technique, a modified extended trochanteric osteotomy incorporating the fracture is utilized to gain access to the loose femoral implant and femoral diaphyseal canal. The femoral diaphyseal canal is then sequentially reamed in 1-mm increments. A fluted tapered stem with the appropriate length, diameter, and axial and rotational stability is inserted into the canal. A proximal body is then chosen that establishes the appropriate leg length, femoral offset, and version. The final proximal body is engaged into the fluted tapered stem. Finally, the fracture is fixed around the implant with a combination of cables or wires. Alternatives: Historically, implants such as extensively porous coated stems were utilized to treat Vancouver B2 or B 3 periprosthetic femoral fractures. Unfortunately, these implants were associated with high rates of failure and revision 7,9 . Rationale: The introduction of a fluted tapered stem provided a more reliable implant that achieves immediate axial and rotational stability. In addition, utilizing a fluted tapered stem allowed for a more soft-tissue-preserving approach to these complex injuries, in turn allowing the fracture to be reduced around the implant proximally with cerclage cables and or wires. Modular fluted tapered stems provide the additional advantage of allowing the surgeon to modify leg length, offset, and femoral version, independently of the fluted tapered stem. As a result of these unique advantages, these stems were introduced several years ago for the treatment of Vancouver B 2 or B 3 periprosthetic femoral fractures. Expected Outcomes: Contemporary series have demonstrated that the use of a modular fluted tapered stem leads to improved implant survivorship and clinical outcomes with lower complication rates for Vancouver B2 and B 3 periprosthetic femoral fractures 1,10–12,14–19 . Important Tips: Template both the fluted tapered stem and proximal body preoperatively. The proximal body should be templated at the ideal hip center of rotation that appropriately restores leg lengths and offset. Template the fluted tapered stem so that it provides appropriate isthmic fit and bypasses the most distal extent of the fracture by at least 2 cortical diameters. Utilize a modified extended trochanteric osteotomy for your exposure in order to facilitate visualization of the fracture and to provide direct access to the femoral canal. Place a prophylactic cable prior to preparing the femur for the implant in order to help prevent iatrogenic fracture. Place a trial stem and obtain intraoperative anteroposterior and lateral radiographs in order to assess the position of the implants and the risk of anterior cortical perforation. When placing the final implants, be sure the fluted tapered stem has both axial and rotational stability. Reduce and fix the fracture after the final implants are placed and the hip is reduced. Acronyms and Abbreviations: AP = anteroposterior MFT = modular fluted tapered (stem) ETO = extended trochanteric osteotomy THA = total hip arthroplasty CT = computed tomography PJI = periprosthetic joint infection

Background: Removal of well-fixed femoral components during revision total hip arthroplasty (THA) can be difficult and time-consuming 1 , leading to numerous complications, such as femoral perforation, bone loss, and fracture. Extended trochanteric osteotomies (ETOs), which provide wide exposure and direct access to the femoral canal under controlled conditions, have become a popular method to circumvent these challenges. ETOs were popularized by Wagner (i.e., the anterior-based osteotomy), and later modified by Paprosky (i.e., the lateral-based osteotomy) 2 . Description: The decision to utilize the laterally based Paprosky ETO versus the anteriorly based Wagner ETO is primarily based on surgeon preference, the location and type of in situ implants, and the osseous anatomy. Typically, a laterally based ETO is most facile in conjunction with a posterior approach and an anteriorly based ETO is most commonly paired with a lateral or anterolateral approach. Attention must be paid to maintaining vascularity to the osteotomy fragment, including minimizing stripping of the vastus lateralis from the osteotomy fragment and maintaining abductor attachments to the osteotomy fragment. When utilizing a laterally based ETO, the posterior border of the vastus lateralis must be carefully elevated to provide exposure for performance of the osteotomy. When an anteriorly based osteotomy is performed, the surgeon may instead extend the abductor tenotomy proximally with use of a longitudinal split of the vastus lateralis distally, which helps to keep the anterior and posterior sleeves of soft tissue in continuity. In either approach, dissection of the vastus lateralis involves managing several large vascular perforators. We prefer performing careful blunt dissection to identify the perforators and prophylactically controlling them, with ligation of large vessels and electrocautery of smaller vessels. Vascular clips are also available in case difficult-to-control bleeding is encountered. In general, an oscillating saw (with preference for a thin blade) is utilized to complete the posterior longitudinal limb of the ETO, extending approximately 12 to 16 cm distally from the tip of the greater trochanter. Although a 12 to 16-cm zone is required to maintain maximum vascularity to the osteotomized fragment, the osteotomy length must ultimately be determined by (1) the length of the femoral component to be removed; (2) the presence of distal bone ingrowth, ongrowth, or cement; and (3) the presence of distal hardware or stemmed knee components. A smaller oscillating saw is then utilized to complete the transverse limb at the previously identified distal extent. A high-speed pencil-tip burr is utilized to complete the corners of the osteotomy in a rounded configuration, and a combination of saws and pencil-tip burrs is utilized to create partial proximal and distal anterior longitudinal limbs of the osteotomy to the extent allowed by the soft-tissue attachments. The anterior longitudinal limb may be further weakened in a controlled fashion with use of serial drill holes. The anterior longitudinal limb then undergoes controlled fracture by placement of 2 to 4 broad straight osteotomes in the posterior longitudinal limb. These osteotomes are carefully levered anteriorly in unison with a gentle, steady force. After the ETO is completed, intramedullary prostheses, hardware, and cement are removed; the acetabulum is addressed as needed; and a final femoral stem is implanted, if appropriate. After completion of the osteotomy, the osteotomized fragment must be retracted gently, with care taken to avoid a fracture and maintain vascularity. To this end, debridement of the endosteum of the osteotomized fragment, including any cement removal, should be avoided until the end of the procedure, when the osteotomy is ready to be closed. Our preferred method for closure is to place 1 prophylactic cable 1 cm distal to the osteotomy, 1 to 2 cables along the diaphyseal segment of the osteotomy, and 1 Luque wire above the less trochanter. A Luque wire is our specific choice for the location above the lesser trochanter because it sits in the effective joint space; however, the use of Luque wires distal to the lesser trochanter is also acceptable. A strut allograft or locking plate can be utilized to reinforce the osteotomy in rare cases or to bridge interprosthetic stress risers. Trochanteric implants are typically avoided because of the low rate of clinically relevant trochanteric migration with this closure technique and because of the high rate of symptomatic implants with trochanteric claws or plates. Alternatives: An alternative osteotomy of similar exposure is the transfemoral osteotomy. Additionally, a variety of non-extended trochanteric osteotomies, such as trochanteric slide osteotomies, offer more limited exposure. Rationale: Femoral surgical exposure for revision THA can be aided by performing transfemoral osteotomies, but these provide less precise control of the separate proximal femoral osteotomized segment(s), and healing and fixation can be less reliable. Less invasive osteotomies such as non-extended trochanteric osteotomies typically do not provide adequate exposure in challenging cases for which ETO is being considered. Expected Outcomes: ETOs have high union rates, and notable trochanteric migration is infrequent. The most common complications are fracture of the osteotomy fragment intraoperatively or postoperatively. Radiographic and clinical union is achieved in 98% of patients. The mean proximal trochanteric osteotomy fragment migration prior to union is 3 mm. ETO fragment migration of >1 cm occurs in just 7% of hips. Postoperative greater trochanter fractures occur in 9% of hips. The 10-year survivorship 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 is 97%, 91%, and 82%, respectively 3 . Important Tips: Attention should be paid to patient anatomy, deformity, surgical approach, and implant type when choosing to perform a laterally based Paprosky or anteriorly based Wagner ETO. Appropriate length of the posterior longitudinal limb of the ETO is approximately 12 to 16 cm distally from the tip of the greater trochanter. Attention must be paid to maintaining vascularity to the osteotomy fragment, including minimizing stripping of the vastus lateralis from the osteotomy fragment and maintaining abductor attachments to the osteotomy fragment. A high-speed pencil-tip burr should be utilized to complete the corners of the osteotomy in a rounded configuration in order to avoid stress risers. The anterior longitudinal limb is completed by controlled fracture of the remaining intervening segment in order to maintain vastus lateralis attachments and vascular supply to the osteotomy fragment. The ETO is closed with use of cerclage cables and/or double-stranded Luque wires, typically utilizing a total of 3 to 4 in order to obtain secure fixation without compromising local biology. Acronyms and Abbreviations: MFT = modular fluted tapered

Background: Dual-mobility (DM) implants reduce the risk of dislocation in patients who have undergone total hip arthroplasty (THA); however, DM implants are at risk for large-head dislocation and intraprosthetic dissociation (IPD), where the inner femoral head dissociates from the outer polyethylene head. This study aimed to report the incidence of DM dislocation and IPD, evaluate the rate of recognition of IPD before and after reduction, investigate the outcomes of these complications, and provide treatment recommendations for their management. Methods: Between 2010 and 2021, 695 primary and 758 revision THAs were performed with DM constructs at a single institution. There were 44 large-head dislocations (3.0%) and 10 IPDs (0.7%). Four additional IPDs occurred during attempted closed reduction, increasing the IPD incidence to 0.96%. We reviewed prior instability history, dislocation management, success of reduction, recognition of IPD, and subsequent rates of revision and complications. The mean follow-up was 2.5 years. Results: Nine of 10 IPDs were missed at presentation and thus not treated as such. Sixty-three percent of attempted closed reductions in the emergency department failed and led to 4 IPDs and 1 periprosthetic fracture. Reduction success was associated with the following factors: use of general anesthesia with paralysis (p = 0.02), having the reduction performed by an orthopaedist (p = 0.03), and undergoing only 1 reduction attempt (p = 0.015). Two-thirds of dislocations required revision. The rate of redislocation was 33%, and 5 hips required subsequent revision at a mean of 1.8 years after the initial dislocation. Conclusions: We present an evaluation of DM-implant dislocation and dissociation along with management recommendations based on these data. Given the low success and high complication rates of attempted closed reduction and the need for eventual revision, we recommend that all patients with dislocated DM implants be brought to the operating room for closed reduction as well as potential revision if the reduction fails. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

AimsContemporary outcomes of primary total hip arthroplasties (THAs) with highly cross-linked polyethylene (HXLPE) liners in patients with inflammatory arthritis have not been well studied. This study examined the implant survivorship, complications, radiological results, and clinical outcomes of THA in patients with inflammatory arthritis.MethodsWe identified 418 hips (350 patients) with a primary diagnosis of inflammatory arthritis who underwent primary THA with HXLPE liners from January 2000 to December 2017. Of these hips, 68% had rheumatoid arthritis (n = 286), 13% ankylosing spondylitis (n = 53), 7% juvenile rheumatoid arthritis (n = 29), 6% psoriatic arthritis (n = 24), 5% systemic lupus erythematosus (n = 23), and 1% scleroderma (n = 3). Mean age was 58 years (SD 14.8), 66.3% were female (n = 277), and mean BMI was 29 kg/m2 (SD 7). Uncemented femoral components were used in 77% of cases (n = 320). Uncemented acetabular components were used in all patients. Competing risk analysis was used accounting for death. Mean follow-up was 4.5 years (2 to 18).ResultsThe ten-year cumulative incidence of any revision was 3%, and was highest in psoriatic arthritis patients (16%). The most common indications for the 15 revisions were dislocations (n = 8) and periprosthetic joint infections (PJI; n = 4, all on disease-modifying antirheumatic drugs (DMARDs)). The ten-year cumulative incidence of reoperation was 6.1%, with the most common indications being wound infections (six cases, four on DMARDs) and postoperative periprosthetic femur fractures (two cases, both uncemented femoral components). The ten-year cumulative incidence of complications not requiring reoperation was 13.1%, with the most common being intraoperative periprosthetic femur fracture (15 cases, 14 uncemented femoral components; p = 0.13). Radiological evidence of early femoral component subsidence was observed in six cases (all uncemented). Only one femoral component ultimately developed aseptic loosening. Harris Hip Scores substantially improved (p < 0.001).ConclusionContemporary primary THAs with HXLPE in patients with inflammatory arthritis had excellent survivorship and good functional outcomes regardless of fixation method. Dislocation, PJI, and periprosthetic fracture were the most common complications in this cohort with inflammatory arthritis.Cite this article: Bone Joint J 2023;105-B(7):768–774.

AimsKnowledge on total knee arthroplasties (TKAs) in patients with a history of poliomyelitis is limited. This study compared implant survivorship and clinical outcomes among affected and unaffected limbs in patients with sequelae of poliomyelitis undergoing TKAs.MethodsA retrospective review of our total joint registry identified 94 patients with post-polio syndrome undergoing 116 primary TKAs between January 2000 and December 2019. The mean age was 70 years (33 to 86) with 56% males (n = 65) and a mean BMI of 31 kg/m2 (18 to 49). Rotating hinge TKAs were used in 14 of 63 affected limbs (22%), but not in any of the 53 unaffected limbs. Kaplan-Meier survivorship analyses were completed. The mean follow-up was eight years (2 to 19).ResultsThe ten-year survivorship free from revision was 91% (95% confidence interval (CI) 81 to 100) in affected and 84% (95% CI 68 to 100) in unaffected limbs. There were six revisions in affected limbs: three for periprosthetic femoral fractures and one each for periprosthetic joint infection (PJI), patellar clunk syndrome, and instability. Unaffected limbs were revised in four cases: two for instability and one each for PJI and tibial component loosening. The ten-year survivorship free from any reoperation was 86% (95% CI 75 to 97) and 80% (95% CI 64 to 99) in affected and unaffected limbs, respectively. There were three additional reoperations among affected and two in unaffected limbs. There were 12 nonoperative complications, including four periprosthetic fractures. Arthrofibrosis occurred in five affected (8%) and two unaffected limbs (4%). Postoperative range of motion decreased with 31% achieving less than 90° knee flexion by five years.ConclusionTKAs in post-polio patients are complex cases associated with instability, and one in four require constraint on the affected side. Periprosthetic fracture was the main mode of failure. Arthrofibrosis rates were high and twice as frequent in affected limbs.Cite this article: Bone Joint J 2023;105-B(6):635–640.

AimsNonagenarians (aged 90 to 99 years) have experienced the fastest percent decile population growth in the USA recently, with a consequent increase in the prevalence of nonagenarians living with joint arthroplasties. As such, the number of revision total hip arthroplasties (THAs) and total knee arthroplasties (TKAs) in nonagenarians is expected to increase. We aimed to determine the mortality rate, implant survivorship, and complications of nonagenarians undergoing aseptic revision THAs and revision TKAs.MethodsOur institutional total joint registry was used to identify 96 nonagenarians who underwent 97 aseptic revisions (78 hips and 19 knees) between 1997 and 2018. The most common indications were aseptic loosening and periprosthetic fracture for both revision THAs and revision TKAs. Mean age at revision was 92 years (90 to 98), mean BMI was 27 kg/m2 (16 to 47), and 67% (n = 65) were female. Mean time between primary and revision was 18 years (SD 9). Kaplan-Meier survival was used for patient mortality, and compared to age- and sex-matched control populations. Reoperation risk was assessed using cumulative incidence with death as a competing risk. Mean follow-up was five years.ResultsMortality rates were 9%, 18%, 26%, and 62% at 90 days, one year, two years, and five years, respectively, but similar to control populations. There were 43 surgical complications and five reoperations, resulting in a cumulative incidence of reoperation of 4% at five years. Medical complications were common, with a cumulative incidence of 65% at 90 days. Revisions for periprosthetic fractures were associated with higher mortality and higher 90-day risk of medical complications compared to revisions for aseptic loosening.ConclusionContemporary revision THAs and TKAs appeared to be relatively safe in selected nonagenarians managed with multidisciplinary teams. Cause of revision affected morbidity and mortality risks. While early medical and surgical complications were frequent, they seldom resulted in reoperation.Cite this article: Bone Joint J 2023;105-B(6):649–656.