Background. A limited number of investigations with conflicting results have described perivascular
Introduction: Metal/metal total hip arthroplasties (THA) with improved qualities of the alloys and encouraging midterm clinical results are widely used. Hyperergic reactions have been observed in revision tissues in a series of failures. This study examined synovial fluids of patients with aseptic loosening of THA from metal/metal and ceramic/polyethylene endoprostheses or arthritis of the hip by analysis of various released cytokines. Materials and Methods: The aspirations of synovial fluids from 11 patients with arthritis of the hip, 6 THA revisions with ceramic polyethylene articulations, and 22 metal/metal articulations were retrieved. 15 of the 22 cases showed
Soft tissue sarcomas (STS) are rare, aggressive malignancies derived from connective tissues such as muscle and fat. Undifferentiated pleomorphic sarcoma (UPS) is one of the most common STS in adults. UPS is an aggressive, highly metastatic sarcoma, and is resistant to chemotherapy. New therapies for UPS are desperately needed. STS have an immune desert tumour immune microenvironment (TIME), characterized by a paucity of tumour infiltrating lymphocytes and subsequent resistance to immunotherapies such as immune checkpoint inhibitors. Strategies capable of creating an immune-rich, inflamed TIME may improve immunotherapy efficacies for sarcoma. Activation of the STING (stimulator of interferon genes) receptor can induce potent innate and adaptive immune responses within immunogenic solid tumours. However, this approach has never been attempted in immune-inert sarcomas. Purpose: To determine the therapeutic anti-tumour effects of STING activation in UPS tumours. We have developed an inducible, immune-competent mouse model of UPS. We evaluated intra-tumoural injection of the murine STING receptor agonist, DMXAA, into UPS-bearing immune-competent mice. DMXAA was injected into palpable UPS tumours of the hindlimb. Tumour volume and bioluminescence imaging was recorded bi-weekly. DMXAA treated UPS tumours were also evaluated for necrosis and immune infiltration at defined time points. UPS tumours developed necrosis and
Introduction. The utilization of lymphocyte transformation testing (LTT) has increased for diagnosing metal sensitivity associated with TKA, but its validity for the diagnosis of TKA failure due to an immune reaction has not been established. Methods. We performed a retrospective study of 27 well-fixed, aseptic primary TKAs with persistent pain and/or stiffness, revised by a single, experienced surgeon for suspected metal allergy to nickel based on a positive LTT. Periprosthetic tissue samples obtained at the time of revision surgery were scored using the aseptic lymphocytic vasculitis-associated lesion (ALVAL) scoring system. Results. Eight patients were categorized as mildly reactive, 8 reactive, and 11 highly reactive to nickel by LTT. The predominant findings on routine histology were fibrosis and varying degrees of
60 out of total series of 643 metal-on-metal hip replacements, carried out over the last nine years, have so far required revision, 13 for peri-prosthetic fracture and 47 for extensive, symptomatic, peri-articular soft-tissue changes. Dramatic corrosion of generally solidly fixed, cemented stems has been observed and is believed to have resulted in the release of high levels of cobalt chrome ions from the stem surface. The contribution of the metal-to-metal articulation is, as yet, unclear. Not including the fracture cases, plain films have demonstrated little or no abnormality to account for patients’ progressive symptoms. MRI scanning, on the other hand, utilising a technique designed to minimise implant artefact, has correlated very closely with findings at the time of revision surgery. The histological changes, typified by extensive
We report on a group of 20 metal-on-metal resurfaced hips (17 patients) presenting with a soft tissue mass associated with various symptoms. We describe these masses as pseudotumours. All patients underwent plain radiography and fuller investigation with CT, MRI and ultrasound. Where samples were available, histology was performed. All patients in this series were female. Presentation was variable; the most common symptom was pain or discomfort in the hip region. Other symptoms included spontaneous dislocation, nerve palsy, an enlarging mass or a rash. The common histological features were extensive necrosis and
Background. An increased incidence of periprosthetic osteolysis, resulting in loss of biologic fixation, has been recently reported in contemporary THAs with low-carbide metal-on-metal compared to metal-on-polyethylene couple bearings. A hypersensitivity reaction due to Co and Cr debris is reported as a potential cause for failure of THAs with high-carbide bearings, but there are no evidence-based data for this reaction in low-carbide metal-on-metal bearings. Questions/purposes. We investigated whether there were differences in immunologic hypersensitivity reactions in retrievals from revised THAs with COP versus MOM bearing couples. Patients and Methods. We compared newly formed capsule and periprosthetic interface membranes retrieved from revision surgery due to aseptic failure in 20 patients with low-carbide bearings and 13 patients with ceramic-on-polyethylene bearings. For control tissue we obtained samples from the hip capsule during the primary THA implantation in 13 patients with low-carbide bearings and seven with ceramic-on-polyethylene. We examined the tissues with conventional histologic and immunohistochemical methods. Results. Compared to the controls and the tissue from patients with ceramic-on-polyethylene bearings, the tissues from patients with low-carbide metal-on-metal bearings were associated with (1) extensive necrosis and fibrin exudation in the newly formed hip capsule and (2) diffuse and perivascular
Introduction: We report on a group of 20 metal-on-metal resurfaced hips (17 patients) presenting with a soft tissue mass associated with various symptoms; these masses we termed pseudotumours. All patients underwent plane radiography; CT, MRI and ultrasound investigations were also performed for some patients. Where samples were available histology was performed. Methods: All patients in this series were female. Presentation was variable; the most common symptom was pain or discomfort in the hip region. Other symptoms included spontaneous dislocation, nerve palsy, a noticeable mass or a rash. The common histological features were extensive necrosis and
The histopathology of periprosthetic tissues has been important to understanding the relationship between wear debris and arthroplasty outcome. In a landmark 1977paper, Willert and Semlitsch (1) used a semiquantitative rating to show that tissue reactions largely reflected the extent of particulate debris. Notably, small amounts of debris, including metal, could be eliminated without “overstraining the tissues” but excess debris led to deleterious changes. Currently, a plethora of terms is used to describe tissues from metal-on-metal (M-M) hips and corroded modular connections. We reviewed the evaluation and reporting of local tissue reactions over time, and asked if a dose response has been found between metal and tissue features, and how the use of more standardized terms and quantitative methodologies could reduce the current confusion in terminology. Methods. The PubMed database was searchedbetween 2000 and 2015 for papers using “metal sensitivity /allergy /hypersensitivity, Adverse Local Tissue Reaction (ALTR): osteolysis, metallosis,
Introduction: We report on a group of 20 metal-onmetal resurfaced hips (17 patients) presenting with a soft tissue mass associated with various symptoms; these masses we termed pseudotumours. Methods: All patients underwent plane radiography; CT, MRI and ultrasound investigations were also performed for some patients. Where samples were available histology was performed. Metal ion levels were measured in six patients and one patient had the metal ion levels in the joint fluid measured. Results: All patients in this series were female. Presentation was variable; the most common symptom was pain or discomfort in the hip region. Other symptoms included spontaneous dislocation, nerve palsy, a noticeable mass or a rash. In all cases a soft tissue mass was present in the region of the hip, this was either solid or cystic. The common histological features were extensive necrosis and
Mesenchymal stem cells (MSCs) from bone marrow are multipotent cells capable of forming cartilage, bone, and other connective tissues. The objective of this study was to determine whether the use of allogenic mesenchymal stem cells could functionally heal defect in the distal femoral physis in rabbits without the use of immunosuppressive therapy. An iatrogenic defect was created in the lateral femoral condyle of thirty-two New Zealand white rabbits, 7 weeks old, that weighed 2.25 ? 0.24 kg. Each defect, 3.5 mm in width and 12 mm in length, in the right distal femoral physis was treated with allogenic mesenchymal stem cells in new composite hyaluronate/ collagen type I/fibrin scaffold. The healing response was evaluated radiographically, by MRI (at three weeks and four months after implantation), and also histologically, by Pearls’ reaction and with immunofluorescency (at four months after implantation). The results were compared with the data for the control defects (without stem cell implantation) in left distal femoral physes. In average, right femurs with damaged distal physis and transplanted MSCs grew more in length (0.55? 0.21 cm) as compared with left femurs with physeal defect without stem cell transplantation (0.46? 0.23 cm). Valgus deformity of right femurs with physeal defect and transplanted MSCs was mild (0.2? 0.1°). On the contrary, left femurs with physeal defect without transplantated MSCs showed significant valgus deformity (2.7? 1.6°). For defects treated with allogenic mesenchymal stem cell implants, no adverse immune response and implant rejection were detected in this model. Histologically, no
Background: Osteoarthritis (OA) is a common phenomena in the population. About 80% of the patients more than 55 years of age have reontgenographic signs of OA, while 25% have clinical signs. Eventually OA leads to joint destruction, which may necessitate joint replacement. Aims: Our goal was to evaluate the synovial reaction in 10 patients who suffered from arthritis and thus underwent total knee replacement operation. Methods: Ten patients with arthritis of the knee joint (8 with OA and 2 with rheumatoid arthritis (RA) who underwent total knee replacement were evaluated. Age ranged between 66 and 79 years (mean 71 years). A control group consisted of 6 cadaver knees (mean age 31 years) with no previous history of knee problems. All the patients in the research group were graded functionally for their knee score by the system of Hospital for Special Surgery Functional Score. Additional plain X-ray score on a three point scale was performed. During surgery macroscopic changes on the articular surface of all three compartments were recorded on a four point scale. Synovial specimens were taken from each compartment for microscopic examination. Results: In the research group the average knee score was 54. The macroscopic changes were found predominantly in the medial compartment. No correlation was found between microscopic and histological changes in the synovia. However, a statistically significant correlation between radiological changes in the medial and lateral compartments and macroscopic changes was noted. In the OA patients the ratio of T to B cells was 60% in favor of the B cells, in contrast to RA which was 75% in favor of T cells. In the control group the common find-ing was a thickened sub-synovial fat layer in the patello-femoral (PF) compartment. Conclusions: Inflammatory reaction in the synovia is graded by the
Recently, a series of locally destructive soft tissue pseudotumour has been reported in patients following metal-on-metal hip resurfacing arthroplasty (MoMHRA), requiring revision surgery in a high percentage of patients. Based on the histological evidence of
Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium. Periprosthetic metal concentrations in the synovia and histopathological samples were analyzed from 230 patients from our institution from October 2016 to December 2019. An ordinal regression model was calculated to investigate the effect of the accumulated metals on the histopathological reaction of the synovia.Aims
Methods
The COVID-19 pandemic has led to unprecedented times worldwide. From lockdowns to masks now being part of our everyday routine, to the halting of elective surgeries, the virus has touched everyone and every part of our personal and professional lives. Perhaps, now more than ever, our ability to adapt, change and persevere is critical to our survival. This year's closed meeting of The Knee Society demonstrated exactly those characteristics. When it became evident that an in-person meeting would not be feasible, The Knee Society leadership, under the direction of President John Callaghan, MD and Program Chair Craig Della Valle, MD created a unique and engaging meeting held on September 10–12, 2020. Special recognition should be given to Olga Foley and Cynthia Garcia at The Knee Society for their flexibility and creativeness in putting together a world-class flawless virtual program. The Bone & Joint Journal is very pleased to partner with The Knee Society to once again publish the proceedings of the closed meeting of the Knee Society. The Knee Society is a United States based society of highly selected members who have shown leadership in education and research in knee surgery. It invites up to 15% international members; this includes some of the key opinion leaders in knee surgery from outside the USA. Each year, the top research papers from The Knee Society meeting will be published and made available to the wider orthopaedic community in The Bone & Joint Journal. The first such proceedings were published in BJJ in 2019. International dissemination should help to fulfil the mission and vision of the Knee Society of advancing the care of patients with knee disorders through leadership, education and research. The quality of dissemination that The Bone & Joint Journal provides should enhance the profile of this work and allow a larger body of surgeons, associated healthcare professionals and patients to benefit from the expertise of the members of The Knee Society. The meeting is one of the highlights of the annual academic calendar for knee surgeons. With nearly every member in attendance virtually throughout the 3 days, the top research papers from the membership were presented and discussed in a virtual format that allowed for lively interaction and discussion. There are 75 abstracts presented. More selective proceedings with full papers will be available after a robust peer review process in 2021, both online and in The Bone & Joint Journal. The meeting commenced with the first group of scientific papers focused on Periprosthetic Joint Infection. Dr Berry and colleagues from the Mayo Clinic further help to clarify the issue of serology and aspirate results to diagnose TKA PJI in the acute postoperative setting. 177 TKA's had an aspiration within 12 weeks and 22 were proven to have PJI. Their results demonstrated that acute PJI after TKA should be suspected within 6 weeks if CRP is ≥81 mg/L, synovial WBCs are ≥8500 cells/μL, and/or synovial neutrophils≥86%. Between 6– 12 weeks, concerning thresholds include a CRP ≥ 32 mg/L, synovial WBC ≥7450, and synovial neutrophils ≥ 84%. While historically the results of a DAIR procedure for PJI have been variable, Tom Fehring's study showed promise with the local delivery of vancomycin through the Intraosseous route improved early results. New member Simon Young contrasted the efficacy of the DAIR procedure when comparing early infections to late acute hematogenous PJI. DAIR failed in 63% of late hematogenous PJIs (implant age>1 year) compared to 36% of early (<1year) PJIs. Dr Masri demonstrated in a small group of patients that those with well-functioning articulating spacers can retain their spacers for over 12 months with no difference in infection from those that had a formal two stage exchange. The mental toll of PJI was demonstrated in a longitudinal study by Doug Dennis, where patient being treated with 2 stage exchange had 4x higher rates of depression compared to patient undergoing aseptic revision. The second session focused on both postoperative issues with regards to anticoagulation and manipulation. Steven Haas demonstrated high complication rates with utilization of anticoagulation for treatment of postoperative pulmonary embolism with modern therapeutic anticoagulation (warfarin, enoxaparin, Xa inhibitors) with the Xa inhibitors demonstrating lower complication rates. Two papers focused on the topic of manipulation. Mark Pagnano presented data on timing of manipulation under anesthesia up to even past 12 months. While gains were modest, a subset of patients did achieve substantial gains in ROM > 20degrees even after 3 months post op. Dr Westrich's study demonstrated no difference in MUA outcomes with either IV sedation or neuraxial anesthesia although the length of stay was shorter in the IV sedation group. Several studies in Session II focused on kinematics and femoral component position. Dr Li's in vivo kinematic study during weightbearing flexion and gait demonstrated that several knees rotated with a lateral pivot motion and not all knees can be described with a single motion character. Dr Mayman and his group utilized a computational knee model to demonstrate that additional distal femoral resection results in increasing levels of mid -flexion instability and cautioned against the use of additional bony resection as the first line for flexion contractures. Using computer navigation, Dr Huddleston's study nicely outlined the variability in femoral component rotation to achieve a rectangular flexion gap utilizing a gap balanced method. The third session opened the meeting on Friday morning. The focus was on unicompartmental knee arthroplasty and the increasing utilization of robotic assisted total knee arthroplasty. David Murray showed using registry data that for patient with higher comorbidities (ASA >3), UKA was safer and more cost effective than TKA while Dr Della Valle's group demonstrated overall lower average healthcare costs in UKA patients compared to TKA in the first 10 years after surgery. Dr Geller assessed UKA survivorship among 3 international registries. While survivorship varied by nation and designs, certain designs consistently had better overall performance. Dr Nunley and his group showed robotic navigation UKA significantly reduced outliers in alignment and overhang compared to manual UKA. Dr Catani's data demonstrated that full thickness cartilage loss should still be considered a requirement for UKA success even with robotic assistance. Despite a high dislocation rate of 4%, Mr Dodd demonstrated high survivorship for lateral UKA despite historical contraindications. The growing evidence for robotics TKA was demonstrated in two studies. Professor Haddad showed less soft tissue injury, reduced bone trauma and improved accuracy or rTKA compared to manual TKA while Dr Gustke single surgeon study showed his rTKA had improved forgotten joint scores and less ligament releasing required for balancing. Despite these finding, Dr Lee's study demonstrated that a robotic TKA could not guarantee excellent pain relief and other factors such a patient expectations and psychological factors play a role. Our fourth session was devoted to machine learning and smart tools and modeling. Dr Meneghini used machine learning algorithms to identify optimal alignment outcomes that correlated with patient outcomes. Several parameters such as native tibial slope, femoral sagittal position and coronal limb alignment correlated with outcomes. Along the same lines, Bozic and coauthors demonstrated that using AI algorithms incorporated with PROM's improved levels of shared decision making and patient satisfaction. Dr Lombardi demonstrated that a mobile patient engagement platform that provided smart phone-based exercise and education was comparable to traditional methods. Dr Mahfouz demonstrated the accuracy of using ultrasound to produce 3D models of the bone compared to conventional CT based strategies and Dr Mahoney showed the valued of a preop 3D model in reproducing more normal knee kinematics. The last two talks of the session focused on some of the positives of the COVID-19 pandemic, namely the embracing of telemedicine by patients and surgeons as demonstrated by Dr Slover and the increasing and far reaching educational opportunities made available to residents and fellows during the pandemic. Session five focused on risk stratification and optimization prior to TKA. Dr O'Connor demonstrated that that the implementation of an optimization program preoperatively reduced length of stay and ED visits, and Charles Nelson's study showed that risk stratification tool can lower complication rates in obese patients undergoing TKA comparable to those that are nonobese. Dr Markel's study demonstrated that those who have preoperative depression and anxiety are at higher risk of complications and readmissions after surgery and these issues should be addressed preoperatively. Interestingly, a study by Dr Callaghan demonstrated that care improvement pathways have not lowered the gap in complications for morbidly obese patients undergoing TKA, Dr Barsoum argued that the overall complication rates were low and this patient cohort had significant gains in PROMS after TKA that would not be experienced if arbitrary cutoff for limited surgery were established. The final session on Friday, Session six, had several well done and interesting studies. There continues to be mounting evidence that liposomal bupivacaine has little effect on managing post-operative pain to warrant its increased use. Bill Macaulay and colleagues showed no change in pain scores, opioid consumption and functional scores when liposomal bupivacaine was discontinued at a large academic medical center. Dr Bugbee importantly demonstrated that a supervised ambulation program reduced falls in the early postoperative period. Several paper on healthcare economics were presented. Rich Iorio showed that stratifying complexity of total joint cases between hospitals with a system can be efficient and cost savings while Dr Jiranek demonstrated in his study that complex TKAs can be identified preoperatively and are associated with prolonged operative time and cost of care and consideration should be given in future reimbursement models to a complexity modifier. Dr Springer, in their evaluation of Medicare bundled payment models, demonstrated that providers and hospitals in historical bundled models that became efficient were penalized in the new model, forcing many groups to drop out and return to a fee for service model. Ron Delanois important work showed that social determinants can have a major negative impact on outcomes following TKA. Our final day on Saturday opened with Session seven, and several interesting paper on metal ions/debris in TKA. Dr Whitesides simulator study showed the absence of scratches and material loss in a ceramic TKA compared with Co-Cr TKA and suggested an advantage to this material in patients with metal sensitivity. Conversely, in a histological study of failed TKA, perivascular
Metal allergy in knee arthroplasty patients is a controversial topic. We aimed to conduct a scoping review to clarify the management of metal allergy in primary and revision total knee arthroplasty (TKA). Studies were identified by searching electronic databases: Cochrane Central Register of Controlled Trials, Ovid MEDLINE, and Embase, from their inception to November 2020, for studies evaluating TKA patients with metal hypersensitivity/allergy. All studies reporting on diagnosing or managing metal hypersensitivity in TKA were included. Data were extracted and summarized based on study design, study population, interventions and outcomes. A practical guide is then formulated based on the available evidence.Aims
Methods
We investigated the reliability of the cobalt-chromium (CoCr) synovial joint fluid ratio (JFR) in identifying the presence of a severe aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) response and/or suboptimal taper performance (SOTP) following metal-on-metal (MoM) hip arthroplasty. We then examined the possibility that the CoCr JFR may influence the serum partitioning of Co and Cr. For part A, we included all revision surgeries carried out at our unit with the relevant data, including volumetric wear analysis, joint fluid (JF) Co and Cr concentrations, and ALVAL grade (n = 315). Receiver operating characteristic curves were constructed to assess the reliability of the CoCr JFR in identifying severe ALVAL and/or SOTP. For part B, we included only patients with unilateral prostheses who had given matched serum and whole blood samples for Co and Cr analysis (n = 155). Multiple regression was used to examine the influence of JF concentrations on the serum partitioning of Co and Cr in the blood.Objectives
Methods
We have encountered patients who developed large joint fluid collections with massive elevations in chromium (Cr) and cobalt (Co) concentrations following metal-on-metal (MoM) hip arthroplasties. In some cases, retrieval analysis determined that these ion concentrations could not be explained simply by the wear rates of the components. We hypothesized that these effects may be associated with aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL). We examined the influence of the ALVAL grade on synovial fluid Co and Cr concentrations following adjustment for patient and device variables, including volumetric wear rates. Initially restricting the analysis to include only patients with one MoM hip resurfacing device, we performed multiple regression analyses of prospectively collected data. We then repeated the same statistical approach using results from a larger cohort with different MoM designs, including total hip arthroplasties.Objectives
Patients and Methods
T-cells are considered to play an important role in the inflammatory response causing arthroplasty failure. The study objectives were to investigate the composition and distribution of CD4+ T-cell phenotypes in the peripheral blood (PB) and synovial fluid (SF) of patients undergoing revision surgery for failed metal-on-metal (MoM) and metal-on-polyethylene (MoP) hip arthroplasties, and in patients awaiting total hip arthroplasty. In this prospective case-control study, PB and SF were obtained from 22 patients (23 hips) undergoing revision of MoM (n = 14) and MoP (n = 9) hip arthroplasties, with eight controls provided from primary hip osteoarthritis cases awaiting arthroplasty. Lymphocyte subtypes in samples were analysed using flow cytometry.Objectives
Methods