Aims. A limited number of investigations with conflicting results have described perivascular lymphocytic infiltration (PVLI) in the setting of total knee arthroplasty (TKA). The purpose of this study was to determine if PVLI found in TKAs at the time of aseptic revision surgery was associated with worse clinical outcomes and survivorship. Methods. A retrospective review was conducted on 617 patients who underwent aseptic TKA revision who had histological analysis for PVLI at the time of surgery. Clinical and radiological data were obtained pre- and postoperatively, six weeks postoperatively, and then every year thereafter. Results. Within this cohort, 118 patients (19.1%) were found to have PVLI on histological analysis. Re-revision was performed on 83 patients (13.4%) with no significant differences in all-cause or aseptic revisions between groups. A higher incidence of PVLI was noted in female patients (p = 0.037). There was no significant difference in improvement in the range of motion (p = 0.536), or improvement of KSC (p = 0.66), KSP (p = 0.61), or KSF (p = 0.3) clinical outcome scores between PVLI and no PVLI sub-groups. There was a higher incidence of a preoperative diagnosis of pain in the PVLI group compared with patients without PVLI (p = 0.002) present. Conclusion. PVLI found on large-scale histological analysis in TKAs at aseptic revision surgery was not associated with worse clinical outcomes or rates of re-revision. Cite this article: Bone Joint J 2021;103-B(6 Supple A):145–149

Background. A limited number of investigations with conflicting results have described perivascular lymphocytic infiltration (PVLI) in the setting of total knee arthroplasty. The purpose of this study was to determine if PVLI found in total knee replacements at the time of aseptic revision surgery was associated with worse clinical outcomes and survivorship. Methods. A retrospective review was conducted on 617 patients that underwent aseptic total knee arthroplasty revision who had histologic analysis for PVLI at the time of surgery. Clinical and radiographic data was obtained pre and postoperatively, 6 weeks post operatively, and then every year thereafter. Results. Within this cohort, 118 patients (19.1%) were found to have PVLI on histologic analysis. A higher incidence of PVLI was noted in female patients (p = 0.037) and those patients with a preoperative diagnosis of unexplained pain (p=0.002). Re-revision was performed on 83 patients (13.4%) with no significant differences in all-cause or aseptic revisions between groups. There was no significant difference in range of motion improvement (p = 0.54), or improvement of KSC (p = 0.66), KSP (p = 0.61), or KSF (p = 0.3) clinical outcome scores between PVLI and no PVLI sub-groups. Conclusion. Perivascular lymphocytic infiltration found on large-scale histologic analysis in total knee replacements at aseptic revision surgery was not associated with worse clinical outcomes or difference in revision rates

We investigated the clinical response to arthroscopic synovectomy in patients with undifferentiated chronic monoarthritis (UCMA) of the wrist. Arthroscopic synovectomy was performed on 20 wrists in 20 patients with UCMA of the wrist who had not responded to non-steroidal anti-inflammatory drugs. The mean duration of symptoms at the time of surgery was 4.3 months (3 to 7) and the mean follow-up was 51.8 months (24 to 94). Inflamed synovium was completely removed from the radiocarpal, midcarpal and distal radioulnar joints using more portals than normal. After surgery, nine patients had early remission of synovitis and 11 with uncontrolled synovitis received antirheumatic medication. Overall, there was significant improvement in terms of pain relief, range of movement and Mayo score. Radiological deterioration was seen in five patients who were diagnosed as having rheumatoid arthritis during the follow-up period. Lymphoid follicles and severe lymphocyte infiltration were seen more often in synovial biopsies from patients with uncontrolled synovitis.

These results suggest that arthroscopic synovectomy provides pain relief and functional improvement, and allows rapid resolution of synovitis in about half of patients with UCMA of the wrist.

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 lymphocytic infiltration in the histologies. The aspirates were examined with a commercially available assay using a Multiplex Reader. The interleukins Il-1 beta, -2, -5, -6, -10, -12, -13, -15,-17 and IL-1 receptor antagonist (Il-1ra) were measured. Further G-CSF, GM-CSF, IFN gamma, MIP 1 beta, MIP alpha, MCP 1, and TNF alpha were assayed. Results: Samples from patients with aseptic loosenings showed increased Il-10 and MCP compared to osteoarthritis. TNF alpha, MIP alpha, and Il-1β were increased in metal/metal THA. Il-5, Il-12, Il-13 and Il-17 were only increased in patients with lymphocytic reactions, but not in ceramic/polyethylene articulations. GM-CSF, G-CSF, IFN gamma, Il-1ra Il-2, and Il-6 were only elevated in THA with lymphocytic reactions compared to metal/metal cases without. Diskussion: Aspirates from aseptic loosened THA are important diagnostic tools. The data showed a distinctly different cytokine profile joint fluids in aseptic loosenings of metal/metal THA vs. ceramic-UHMWPE articulations and fluids from osteoarthritis patients. The data may contribute to establish a cytokine profile to determine failures due to lymphocytic infiltrations before revision of metal/metal articulations

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 lymphocytic infiltration 72 hours after DMXAA treatment. A single intra-tumoural dose of DMXAA into UPS tumours resulted in durable cure in 50% of mice. All survivors rejected a re-challenge of the UPS tumours in both the contralateral hindlimb and lung, suggesting adaptive immunity. The therapeutic effects of DMXAA were mitigated in lymphocyte deficient Rag2 knockout mice. STING therapy is a promising immunotherapeutic opportunity for immune-inert sarcomas. Our data warrants further preclinical investigations in other sarcoma models and in combination with other immune-based therapies

We report 17 patients (20 hips) in whom metal-on-metal resurfacing had been performed and who presented with various symptoms and a soft-tissue mass which we termed a pseudotumour. Each patient underwent plain radiography and in some, CT, MRI and ultrasonography were also performed. In addition, histological examination of available samples was undertaken. All the patients were women and their presentation was variable. The most common symptom was discomfort in the region of the hip. Other symptoms included spontaneous dislocation, nerve palsy, a noticeable mass or a rash. The common histological features were extensive necrosis and lymphocytic infiltration. To date, 13 of the 20 hips have required revision to a conventional hip replacement. Two are awaiting revision. We estimate that approximately 1% of patients who have a metal-on-metal resurfacing develop a pseudotumour within five years. The cause is unknown and is probably multifactorial. There may be a toxic reaction to an excess of particulate metal wear debris or a hypersensitivity reaction to a normal amount of metal debris. We are concerned that with time the incidence of these pseudotumours may increase. Further investigation is required to define their cause

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 lymphocytic infiltration in 17/27 (63%) of the cases. The average ALVAL score of the cohort was 3.1 ± 1.9, out of a maximum score of 10. Average Knee Society Scores (KSS) improved post-revision, as did range of motion (all p<0.01). Neither LTT stimulation index as a continuous variable nor as a categorical variable (mild, moderate, high) was correlated with ALVAL score, pre-operative function, or change in function at last follow-up (0.015 < r < 0.30, 0.13 < p < 0.95) as measured by KSS. In addition, the ALVAL score did not correlate significantly with either pre-operative or post-operative KSS or range of motion (0.061 < r < 0.365, 0.09 < p < 0.88). Conclusions. Based on this analysis including histopathology, LTT results alone are insufficient for the diagnosis of TKA failure due to an immune reaction. A positive LTT may not indicate that an immune reaction is the cause of pain and stiffness post-TKA. The role of LTT in assessing immune failure of TKA needs further investigation. Diagnostic criteria for immune failure of a TKA need to be established

The intermetatarsophalangeal bursa was investigated by dissection, radiography and injection. In the web spaces between the second and third and the third and fourth digits the bursa lies superior to the transverse metatarsal ligament but projects distally to it, closely applied to the neurovascular bundle. Tissue from the web spaces of patients with classical Morton's metatarsalgia often shows lymphocytic infiltration, with additional fibrinoid necrosis of the bursal wall. It is suggested that inflammatory changes in this bursa could account for the pathological and histological findings in this condition. The bursa in the most lateral web space does not extend beyond the ligament and is not in contact with the neurovascular bundle, which may explain the rarity of symptoms in this space

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 lymphocytic infiltration and a severe vasculitis leading to, in some cases, extensive tissue necrosis are demonstrated and discussed. The failure of any of the existing protective mechanisms or regulatory restrictions to identify and limit the exposure of large numbers of patients to unsatisfactory implants has again been demonstrated

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 lymphocytic infiltration. Fourteen of the 20 cases (70%) have so far required revision to a conventional hip replacement and their symptoms have either settled completely or improved substantially since the revision surgery. Two of the three bilateral cases have asymptomatic pseudotumours on the opposite side. We estimate that about 1% of patients develop a pseudotumour in the first five postoperative years after a hip resurfacing. The cause of these pseudotumours is unknown and is probably multi-factorial, further work is required to define this; they may be manifestations of a metal sensitivity response. We are concerned that with time the incidence of these pseudotumours will increase

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 lymphocytic infiltration of a higher degree than in the ceramic-on-polyethylene hips in conventional histologic examination and (3) more T than B cells. Conclusions. The conventional histologic and immunohistochemical findings in tissues retrieved from failed THAs with low-carbide metal-on-metal bearings are consistent with a link between hypersensitivity and osteolysis with low-carbide bearing couple THA

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 lymphocytic infiltration. Fourteen of the 20 cases (70%) have so far required revision to a conventional hip replacement and their symptoms have either settled completely or improved substantially since the revision surgery. Two of the three bilateral cases have asymptomatic pseudotumours on the opposite side. Conclusions: We estimate that about 1% of patients develop a pseudotumour in the first five postoperative years after a hip resurfacing. The cause of these pseudotumours is unknown and is probably multi-factorial, further work is required to define this; they may be manifestations of a metal sensitivity response. We are concerned that with time the incidence of these pseudotumours will increase

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, lymphocytic infiltration, Aseptic Lymphocytic Vasculitis-Associated Lesions (ALVAL), Adverse Reaction to Metal Debris (ARMD) or pseudotumor/ pseudotumour” as well as metal-on-metal / metal-metal AND hip arthroplasty/replacement. Reports lacking soft tissue histological analysis were excluded. Results. 131 articles describing M-M tissue histology were found. In earlier studies, the terms metal sensitivity / hypersensitivity /allergy implied or stated the potential for a Type IV delayed type hypersensitivity response as a reason for revision. More recently those terms have largely been replaced by broader terms such as ALTR, ALVAL and ARMD. ALVAL and metal hypersensitivity were often used interchangeably, both as failure modes and histological findings. Several histology scoring systems have been published but were only used in a limited number of studies. Correlations of histological features with metal levels or component wear were inconclusive, typically because of a high degree of variability. Interestingly, there were very few descriptions that concluded that the observed reactions were benign / normal or anticipated i.e. regardless of the histological features, extent of debris or failure mode, the histology was interpreted as showing an adverse reaction. Discussion. There is now an expanded set of terms to describe tissues but they lack clear definitions and typically do not use quantitative histological data to describe a wide range of periprosthetic reactions to metal. Lower limits of inflammation, necrosis or re-organization that represent a “normal” reaction to surgery and/or small amounts of wear debris are not clearly defined and are rarely discussed. The widespread adoption of the term “adverse” in the present tissue lexicon implies a cause and effect relationship between metal wear and corrosion products and histological features even though this has yet to be determined. The use of quantitative histological scores rather than subjective histological descriptions is imperative to improve the understanding and reporting of the range of periprosthetic reactions. In particular, a new lexicon that allows for a level of tissue reaction that is not misinterpreted as adverse is required

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 lymphocytic infiltration. The blood cobalt and chromium levels varied considerably between the six patients that had these measurements. The median blood chromium level was 3.8 μg/L (range 0.8 to 23 μg/L) and that for cobalt was 11.5 μg/L (range 2.1 to 15 μg/L). The synovial fluid sample taken from a single joint contained much higher metal levels, 701 μg/L for chromium and 329 μg/L for cobalt. Twelve of the 20 cases have so far required revision to a conventional hip replacement. Discussion: This complication is best imaged with ultrasound, and is not detected by normal xray. We estimate that about 1% of patients develop a pseudotumour in the first five postoperative years. The cause of these pseudotumours is unknown and is probably multifactorial, further work is required to define this; they may be manifestations of a metal sensitivity response. We are concerned that with time the incidence of these pseudo-tumours will increase

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 lymphocytic infiltration occurred. At four months after transplantation, hyalinne cartilage had formed throughout the defects treated with allogenic MSCs. Labeled mesenchymal stem cells/diferentiated chondrocytes were detected in the physeal defects based on magnetic resonance imaging and immunofluorescency. The results of this study demonstrated that allogenic mesenchymal stem cells in a new composite hyaluronate/collagen type I/fibrin scaffold repaired iatrogenic defects in the distal femoral physes in rabbits without the use of immunosuppressive therapy. The use of allogenic mesenchymal stem cells for the repair of physeal defects may be an alternative to autologous MSCs transplantation. An allogenic approach would enable mesenchymal stem cells to be isolated from any donor, providing a readily available source of cells for cartilage tissue repair

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 lymphocytic infiltration into the synovia. In OA this is usually mild. However, the predominant reaction is fibrosis. There is no correlation between this fibrotic reaction and overt radiological or macroscopic findings. The thick subsynovial fat layer found in the PF compartment in the control group has not been described previously in the literature and should be the focus of further investigations

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 lymphocytic infiltration, a delayed hypersensitivity reaction to nickel (Ni), chromium (Cr) or cobalt (Co) has been suggested to play a role in its aetiology. The aim of this study was to investigate the incidence and level of hypersensitivity reaction to metals in patients with pseudotumour. Materials and Methods: 25 patients were investigated in this Ethics approved study:. Group 1: MoMHRA patients with pseudotumours, detected on the ultrasound and confirmed with MRI (n=6, 5 F:1 M, mean age 53 years);. Group 2: MoMHRA patients without pseudotumours (n=13, 7 F:6 M, mean age 55 years); and. Group 3: age-matched control subjects without metal implants (n=6, 4 F:2 M, mean age 54 years). Lymphocyte transformation tests (LTT) were used to measure lymphocyte proliferation responses to metals. Peripheral blood mononuclear cells were isolated from heparinized blood samples using standard Ficoll–Hypaque® (Pharmacia). The PBMC were cultured at a cell density of 106 cells/mL. Culture was set up in the presence of either:. medium alone;. nickel chloride (Sigma; 10-4M-10-6M);. cobalt chloride (10-4M-10-6M); and. chromium chloride (10-4M-10-6M). After 5 days of culture, cells were pulsed with [3H]-thymidine and proliferation was assessed by scintillation counting. The stimulation index (SI) was calculated by the ratio of mean counts per minute of stimulated to unstimulated cultures. A SI value of greater than 2.0 was interpreted as a positive result. Results: A clinical history of metal allergy was reported in 2/6 in Group 1, 2/13 in Group 2, and none in Group 3. In pseudotumour group, the incidence of reactivity to Ni, Co and Cr was 60%, 17% and 0%, respectively. Within Group 2, the reactivity to Ni, Co and Cr was 69%, 8% and 15%, respectively. One control subject had reactivity to Ni. Inter-group comparisons of mean SI values (Kruskal-Wallis non-parametric analysis of variance) showed no significant differences (p> 0.05). Discussion: The incidence of enhanced lymphocyte response to metals in patients with MoMHRA was more common than the control group. However, in comparison with non-pseudotumour patients, there was no significant difference in the incidence or the level of lymphocyte reactivity in patients with pseudotumour. We conclude that patients with MoMHRA have an enhanced lymphocyte response to metal ions, reflecting exposure and immune reactivity. However, patients with pseudotumours have a similar proliferative response to those without pseudotumours, which suggests that type IV hypersensitivity may not be the cause of the pseudotumours

Aims

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.

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 lymphocytic infiltration was not associated with worse clinical outcomes or differences in revision in a series of 617 aseptic revisions, 19% of which had PVLI found on histology. The Mayo group and Dr Trousdale however, noted that serum metal ion levels can be helpful in identifying implant failure in a group of revision TKAs, especially those with metallic junctions. Dr Dalury demonstrated nicely that use of maximally conforming inserts did not have a negative effect on implant loosening in a series of 76 revision TKA's at an average follow up of 7 years, while Kevin Garvin and his group showed no difference in end of stem pain between cemented and cementless stems in revision TKA. The final two studies in the session by Bolognesi and Peters respectively showed that metaphyseal cones continue to demonstrate excelled survivorship in rTKA setting despite extensive bone loss. Session eight was highlighted by a large series of revision reported by new member Dr Schwarzkopf, who showed that revision TKA done by high volume surgeons demonstrated better outcomes and lower revision rates compared to surgeon who did less than 18 rTKA's per year. Dr Maniar importantly showed that preoperatively, patients with high activity level and low pain and indicated by a high preop forgotten joint score did poorly following TKA while David Ayers nicely demonstrated that KOOS scores that assess specific postoperative outcomes can predict patient dissatisfaction after TKA. The final paper in this session by Max Courtney showed that the majority of surgical cancellations are due to medical issues, yet a minority of these undergo any intervention specifically for that condition, but they resulted in a delay of 5 months. The first two studies of Session nine focused on polyethylene thickness. Dr Backstein demonstrated no difference in KSS scores, change in ROM and aseptic revision rates based on polyethylene thickness in a series of 195 TKA's. An interesting lab study by Dr Tim Wright showed a surprising consistency in liner thickness choice among varying levels of surgeon experience that did not correlate with applied forces or gap stability estimates. Two studies looked specifically at the issue of tibial loosening and implant design. Nam and colleagues were not able to demonstrate concerning findings for increasing tibial loosening in a tibial baseplate with a shortened tibial keel at short term follow up, while Lachiewicz demonstrated a 19% revision or revision pending rate in 223 cemented fixed bearing ATTUNE TKA at a mean of 30 months. Our final session of the meeting, began with encouraging news, that despite only currently capturing about 40% of TJA's done in the US, the American Joint Replacement Registry data is representative of data in other representative US databases. An interesting study presented by Robert Barrack looked at bone remodeling in the proximal tibia after cemented and cementless TKA of two different designs. No significant difference was noted among the groups with the exception of the cemented thicker cobalt chrome tray which demonstrated significantly more bone mineral density loss. Along the same lines, a study out of Dr Bostrom's lab demonstrated treatment of a murine tibial model with iPTH prevents fibrous tissue formation and enhances bone formation in cementless implants. New Member Jamie Howard showed no difference in implant migration and kinematics of a single radius cementless design using either a measured resection or gap balancing technique and Dr Cushner show no difference in blood loss with cemented or cementless TKA with the use of TKA. The final two studies looked at staging and bilateral TKA's. Peter Sharkey showed that simultaneous TKA's were associated with higher complication compared to staged TKA and that staged TKA with less than a 90-day interval was not associated with higher risk. However, Mark Figgie showed that patients undergoing simultaneous TKA compared to staged TKA, missed 17 fewer days of work. In spite of the virtual nature of the meeting, there were some outstanding scientific interactions and the material presented will continue to generate debate and to guide the direction of knee arthroplasty as we move forwards

Aims

This study aims to assess the relationship between history of pseudotumour formation secondary to metal-on-metal (MoM) implants and periprosthetic joint infection (PJI) rate, as well as establish ESR and CRP thresholds that are suggestive of infection in these patients. We hypothesized that patients with a pseudotumour were at increased risk of infection.