Berry, Daniel J.

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.

AbstractArthrofibrosis, which is characterized by excessive scar tissue and limited motion, can complicate the daily functioning of patients after total knee arthroplasty (TKA). Molecular hallmarks of arthrofibrosis include pathologic accumulation of myofibroblasts and disproportionate collagen deposition. Epigenetic mechanisms, including posttranslation modification of histones, control gene expression and may regulate fibrotic events. This study assessed the role of the bromodomain and extra‐terminal (BET) proteins on myofibroblast differentiation. This group of epigenetic regulators recognize acetylated lysines and are targeted by a class of drugs known as BET inhibitors. RNA‐seq analysis revealed robust mRNA expression of three BET members (BRD2, BRD3, and BRD4) while the fourth member (BRDT) is not expressed in primary TKA knee outgrowth fibroblasts. RT‐qPCR and western blot analyses revealed that BET inhibition with the small molecule JQ1 impairs TGFβ1‐induced expression of ACTA2, a key myofibroblast marker, in primary outgrowth knee fibroblasts. Similarly, JQ1 administration also reduced COL3A1 mRNA levels and collagen deposition as monitored by picrosirius red staining. Interestingly, the inhibitory effects of JQ1 on ACTA2 mRNA and protein expression, as well as COL3A1 expression and collagen deposition, were paralleled by siRNA‐mediated depletion of BRD4. Together, these data reveal that BRD4‐mediated epigenetic events support TGFβ1‐mediated myofibroblast differentiation and collagen deposition as seen in arthrofibrosis. To our knowledge, these are the first studies that assess epigenetic regulators and their downstream events in the context of arthrofibrosis. Future studies may reveal clinical utility for drugs that target epigenetic pathways, specifically BET proteins, in the prevention and treatment of arthrofibrosis.

Aims As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA). Methods Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections. Results Experimental knees immobilized for four weeks demonstrated mean PEAs of 141°, 72°, and 79° after zero, two, and four weeks of remobilization (n = 6 per group), respectively. Experimental knees demonstrated reduced PEAs after two weeks (p < 0.001) and four weeks (p < 0.0001) of remobilization compared to controls. Following eight weeks of immobilization, experimental knees exhibited mean PEAs of 82°, 73°, and 72° after zero, two, and four weeks of remobilization, respectively. Histological analysis demonstrated no cartilage degeneration. Similar trends in biomechanical and histological properties were observed when intra-articular violation was introduced. Conclusion This study established a novel mouse model of robust knee contracture without evidence of OA. This was appreciated consistently after eight weeks of immobilization and was irrespective of length of remobilization. As such, this arthrofibrotic model provides opportunities to investigate molecular pathways and therapeutic strategies. Cite this article: Bone Joint Res 2023;12(1):58–71.

Abstract In rheumatoid synovitis, lymphocytes can be arranged in follicular structures resembling secondary lymphoid follicles. To understand the organizing principles of this ectopic lymphoid tissue, the cellular components contributing to synovial follicles were examined. In 9 of 24 synovial tissue biopsies, lymphoid aggregates were found consisting of CD4+ T cells and CD20+ B cells. In four of the nine patients, the follicular centers were occupied by CD23+ CD21+ cellular networks representing follicular dendritic cells involved in germinal center reactions. In five patients, CD23+ cells were absent from the centers of the aggregates, suggesting that fully developed germinal centers are generated in only a subset of patients. To identify factors involved in the regulation of the synovial microarchitecture, cell populations contributing to the follicles were quantified by digital image analysis of immunostained tissue and by flow cytometry of tissue-derived lymphocytes. Proportions of CD4+, CD20+, and CD68+ cell subsets were surprisingly invariant, irrespective of the presence or absence of CD23+ follicular dendritic cells. Instead, tissue biopsies with CD23+ germinal center-like regions could be distinguished from those with CD23− T cell-B cell aggregates by a fourfold increase in the frequency of tissue-infiltrating CD8+ T cells, a fraction of which expressed CD40 ligand (CD40L). The data suggest a previously unsuspected role of CD8+ lymphocytes in modulating germinal center formation and raise the possibility that CD8+ CD40L+ T cells are involved in aggravating pathologic immune responses in rheumatoid synovitis.

ImportanceIndividuals with total joint arthroplasty (TJA) have long-term exposure to metal-containing implants; however, whether long-term exposure to artificial implants is associated with cognitive function is unknown.ObjectiveTo compare long-term cognitive trajectories in individuals with and without TJA.Design, Setting, and ParticipantsThis population-based cohort study assessed serial cognitive evaluations of 5550 participants (≥50 years of age) from the Mayo Clinic Study of Aging between November 1, 2004, and December 31, 2020.ExposuresTotal joint arthroplasty of the hip or the knee.Main Outcomes and MeasuresLinear mixed-effects models were used to compare the annualized rate of change in global and domain-specific cognitive scores in participants with and without TJA, adjusting for age, sex, educational level, apolipoprotein E ε4 carrier status, and cognitive test practice effects.ResultsA total of 5550 participants (mean [SD] age at baseline, 73.04 [10.02] years; 2830 [51.0%] male) were evaluated. A total of 952 participants had undergone at least 1 TJA of the hip (THA, n = 430) or the knee (TKA, n = 626) before or after entry into the cohort. Participants with TJA were older, more likely to be female, and had a higher body mass index than participants without TJA. No difference was observed in the rate of cognitive decline in participants with and without TJA until 80 years of age. A slightly faster cognitive decline at 80 years or older and more than 8 years from surgery was observed (b = −0.03; 95% CI, −0.04 to −0.02). In stratified analyses by surgery type, the faster decline was observed primarily among older participants with TKA (b = −0.04; 95% CI, −0.06 to −0.02).Conclusions and RelevanceIn this cohort study, long-term cognitive trajectories in individuals with and without TJA were largely similar except for a slightly faster decline among the oldest patients with TKA; however, the magnitude of difference was small and of unknown clinical significance.

Background: Medicare Advantage (MA) plans are popular among Medicare-eligible patients, but little is known about MA in lower-extremity total joint arthroplasty (TJA). The purpose of this study was to describe trends in MA utilization and analyze differences in patient characteristics and postoperative outcomes between patients undergoing primary TJA using traditional Medicare (TM) or MA plans. Methods: Patients ≥65 years of age who underwent primary total knee or total hip arthroplasty were identified using the Premier Healthcare Database. Patients were categorized into TM and MA cohorts. Data from 2004 to 2020 were used to describe trends in insurance coverage. Data from 2015 to 2020 were used to identify differences in patient characteristics and postoperative complications using ICD-10 codes. Multivariate analyses were performed using 2015 to 2020 data to account for potential confounders. Results: From 2004 to 2020, the proportion of patients with MA increased from 7.9% to 34.4%, while those with TM decreased from 83.7% to 54.0%. Of the 697,317 patients who underwent primary elective TJA from 2015 to 2020, 471,439 (67.6%) had TM coverage and 225,878 (32.4%) had MA coverage. The cohorts were similar in terms of age and sex. However, a higher proportion of Black patients (8.29% compared with 4.62%; p < 0.001) and a lower proportion of White patients (84.0% compared with 89.2%; p < 0.001) were enrolled in MA compared with TM. After controlling for confounders, patients with MA had higher odds of surgical site infection (adjusted odds ratio [aOR]: 1.15; 95% confidence interval [CI]: 1.04 to 1.47; p = 0.031), periprosthetic joint infection (aOR: 1.10; 95% CI: 1.03 to 1.18; p = 0.006), stroke (aOR: 1.15; 95% CI: 1.02 to 1.31; p = 0.026), and acute kidney injury (aOR: 1.08; 95% CI: 1.04 to 1.11; p < 0.001), but lower odds of urinary tract infection (aOR: 0.94; 95% CI: 0.90 to 0.98; p = 0.003). Conclusions: From 2004 to 2020, the number of patients utilizing MA increased markedly such that 1 in 3 were covered by MA in 2020. From 2015 to 2020, patients who were non-White were more likely to have MA than TM, and the MA group had a higher rate of several postoperative complications compared with the TM group. As TM claims data inform health-care policy and clinical decisions, this change portends future challenges, including limitations in arthroplasty registry research, an increase in the administrative burden of surgeons, and a potential worsening of social disparities in health care.

Aims Spinal anaesthesia has seen increased use in contemporary primary total knee arthroplasties (TKAs). However, controversy exists about the benefits of spinal in comparison to general anaesthesia in primary TKAs. This study aimed to investigate the pain control, length of stay (LOS), and complications associated with spinal versus general anaesthesia in primary TKAs from a single, high-volume academic centre. Methods We retrospectively identified 17,690 primary TKAs (13,297 patients) from 2001 to 2016 using our institutional total joint registry, where 52% had general anaesthesia and 48% had spinal anaesthesia. Baseline characteristics were similar between cohorts with a mean age of 68 years (SD 10), 58% female (n = 7,669), and mean BMI of 32 kg/m2 (SD 7). Pain was evaluated using oral morphine equivalents (OMEs) and numerical pain rating scale (NPRS) data. Complications including 30- and 90-day readmissions were studied. Data were analyzed using an inverse probability of treatment weighted model based on propensity score that included many patient and surgical factors. Mean follow-up was seven years (2 to 18). Results Patients treated with spinal anaesthesia required fewer postoperative OMEs (p < 0.001) and had lower NPRS scores (p < 0.001). Spinal anaesthesia also had fewer cases of altered mental status (AMS; odds ratio (OR) 1.3; p = 0.044), as well as 30-day (OR 1.4; p < 0.001) and 90-day readmissions (OR 1.5; p < 0.001). General anaesthesia was associated with increased risk of any revision (OR 1.2; p = 0.021) and any reoperation (1.3; p < 0.001). Conclusion In the largest single institutional report to date, we found that spinal anaesthesia was associated with significantly lower OME use, lower risk of AMS, and lower overall 30- and 90-day readmissions following primary TKAs. Additionally, spinal anaesthesia was associated with reduced risk of any revision and any reoperation after accounting for numerous patient and operative factors. When possible and safe, spinal anaesthesia should be considered in primary TKAs. Cite this article: Bone Joint J 2022;104-B(11):1209–1214.

Aims We have previously reported the mid-term outcomes of revision total knee arthroplasty (TKA) for flexion instability. At a mean of four years, there were no re-revisions for instability. The aim of this study was to report the implant survivorship and clinical and radiological outcomes of the same cohort of of patients at a mean follow-up of ten years. Methods The original publication included 60 revision TKAs in 60 patients which were undertaken between 2000 and 2010. The mean age of the patients at the time of revision TKA was 65 years, and 33 (55%) were female. Since that time, 21 patients died, leaving 39 patients (65%) available for analysis. The cumulative incidence of any re-revision with death as a competing risk was calculated. Knee Society Scores (KSSs) were also recorded, and updated radiographs were reviewed. Results The cumulative incidence of any re-revision was 13% at a mean of ten years. At the most recent-follow-up, eight TKAs had been re-revised: three for recurrent flexion instability (two fully revised to varus-valgus constrained implants (VVCs), and one posterior-stabilized (PS) implant converted to VVC, one for global instability (PS to VVC), two for aseptic loosening of the femoral component, and two for periprosthetic joint infection). The ten-year cumulative incidence of any re-revision for instability was 7%. The median KSS improved significantly from 45 (interquartile range (IQR) 40 to 50) preoperatively to 70 (IQR 45 to 80) at a mean follow-up of ten years (p = 0.031). Radiologically, two patients, who had not undergone revision, had evidence of loosening (one tibial and one patellar). The remaining components were well fixed. Conclusion We found fair functional outcomes and implant survivorship at a mean of ten years after revision TKA for flexion instability with a PS implant. Recurrent instability and aseptic loosening were the most common indications for re-revision. Components with increased constraint, such as a VVC or hinged, should be used in these patients in order to reduce the risk of recurrent instability. Cite this article: Bone Joint J 2022;104-B(10):1126–1131.