TKR is often the only management option for patients with severe knee joint damage. Identifying which disease caused the joint damage is essential for guiding treatment plans, given that RA is a systemic, inflammatory disease that may also affect the eyes or lining around the heart, while OA affects just the joints. “We know there are many more immune cells present in the synovium, or joint tissue, of patients with RA compared to those with OA,” said Bella Mehta, MBBS, MS, rheumatologist at HSS and lead author of the study. “But precisely how many more has not been clear.”

“Pathologists typically assess images of synovium to determine the extent of inflammation using a combination of approaches, including assigning the level of immune cell infiltration on a scale from 0 to 4,” said Dana Orange, MD, MS, rheumatologist at HSS, assistant professor at Rockefeller University and senior author of the study. “However, these methods are imperfect.” For example, a recent study by HSS investigators found that assessments from two highly experienced pathologists evaluating the infiltration of one type of immune cells known as lymphocytes on the same slides agreed only 67 percent of the time.¹

Drs. Orange, Mehta and colleagues at HSS and collaborating institutions developed and validated a computer vision tool that rapidly counts tens of thousands of cell nuclei in whole-slide images of synovium.² For their present study, they measured 14 different pathologist-scored features in synovium from 60 patients with RA and 147 patients with OA who underwent TKR, and used the computer vision tool to determine cell density.

The investigators identified significant differences between RA and OA features in synovium. The RA samples showed increased cell density; low numbers of mast cells, a type of white blood cell; and lower evidence of fibrosis or scarring compared to the OA samples. The probability of correctly distinguishing between RA and OA in synovium was 85 percent when using the 14 pathologist-scored features alone, 88 percent when using the computer’s score for cell density alone and 91 percent when the researchers combined the pathologists’ scores and the computer’s cell density calculation. The researchers determined a cutoff point for distinguishing RA from OA, determining that synovium containing more than 3,400 cells per mm² should be classified as RA.

“While our innovation is not ready for clinical use yet, it holds promise for assisting pathologists in the future,” Dr. Orange said. “Right now, we see it as a valuable tool for research purposes because it provides an accurate and 100% reproducible score of inflammation and look forward to developing it further.”

Dr. Orange added that in the future computer vision could be trained to glean other types of information from tissue samples, including which types of cells are present and whether they are close enough together that they are likely to be communicating with each other. This more granular assessment might enable clinicians to know more precisely which cells are causing tissue damage and tailor treatments accordingly.

Authors: Bella Mehta, MBBS, MS, Susan M. Goodman, MD, Edward F. DiCarlo, MD, Deanna Jannat-Khah, J. Alex Gibbons, Miguel Otero, PhD, Laura Donlin, PhD (HSS), Tania Pannellini, MD, PhD (Weill Cornell Medicine), William Robinson, MD, PhD (Stanford University), Peter K. Sculco, MD, Mark P. Figgie, MD, Jose A. Rodriguez, MD (HSS), Jessica Kirschmann (Stanford University), James Thompson, David Slater, Damon Frezza (The MITRE Corporation), Zhenxing Xu, Fei Wang, PhD (Weill Cornell Medicine), Dana Orange, MD, MS (HSS and Rockefeller University).

References

1. Orange DE, Agius P, DiCarlo EF, et al. Identification of Three Rheumatoid Arthritis Disease Subtypes by Machine Learning Integration of Synovial Histologic Features and RNA Sequencing Data. Arthritis Rheumatol. 2018;70(5):690-701. doi:10.1002/art.40428

2. Guan S, Mehta B, Slater D, et al. Rheumatoid Arthritis Synovial Inflammation Quantification Using Computer Vision. ACR Open Rheumatol. 2022;4(4):322-331. doi:10.1002/acr2.11381

"In our study, there were no differences in the functional milestone attainment and at 1 year they were the same. We concluded that both approaches were excellent. There was probably a little more rapid recovery with the direct anterior approach, but everything improved after that," said Dr. Rodriguez during the debate at the Annual Current Concepts in Joint Replacement (CCJR) Spring meeting in Las Vegas, Nevada.

Read the full article at ryortho.com [subscription required].

"[My nurse] talked to Dr. Rodriguez, who said the new hip fit perfectly," he wrote.

"The physical therapist has me [walk] around the hallway on a walker, then takes me to a fake flight of stairs where I practice with a cane," Marquardt added.

This article appeared in the August 16, 2018 print issue.

According to a recent survey, Dr. Rodriguez found that most patients and doctors don't discuss sex after joint replacement surgery, despite the fact that for many it's a key consideration when they decide to undergo hip or knee surgery.

"We know that just like most movement is painful before surgery, and in the overwhelming majority of cases that movement is made markedly less [painful or] not painful after surgery, it affects both their non-sex and their sex life meaningfully," Dr. Rodriguez said.

"With hip surgery performed through a posterior approach… you shouldn't bring your hip up towards your chest, or rotate the knee inwards toward the middle of the body beyond 90 degrees. The reason is that when a posterior approach is performed, the ligaments that hold the hip in place are cut and repaired; and so until that tissue heals, that risk is there," he added.

Additionally, Dr. Rodriguez noted that "for a knee, or for an anterior approach hip [replacement], most surgeons will say when you feel comfortable, you can return to sexual activity."

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"The rate of knee instability in our study is unexpectedly high," said Jose Rodriguez, MD, study co-author and orthopedic surgeon at Hospital for Special Surgery. "Outcomes of patients undergoing a revision for PJI might not be as good as patients might have thought with longer term follow-up."

PJI is one of the most devastating and frequent complications that can occur after lower extremity joint arthroplasty, such as total knee replacement. The incidence of PJI varies by institution, from about .5 to 4 percent, and often requires revision surgery. Multiple procedures are sometimes necessary to eradicate infection and restore functionality, and even with successful eradication of infection, patients may not achieve optimal functional outcomes.

Dr. Rodriguez and colleagues launched their study after recognizing that there were patients who reported that their knees felt looser after they had a TKA revision for PJI. To shed more light on the issue, the researchers reviewed revision TKA cases for PJI involving four arthroplasty surgeons at a single institution in New York City from 2007-2017. Patients who had received a hinged prosthesis at initial reimplantation were excluded from the analysis. The researchers collected data on demographics, patient comorbidities (including diabetes, neuromuscular disorders, inflammatory arthritis, and hip or foot deformity), implant type, subjective reports or objective findings of instability, and need for further surgery.

There were 45 patients in the study, including 27 of whom had a minimum of 1 year of follow up. "Among the patients who had one-year follow-up, 33 percent had functional instability. Their knee moved more than what we would consider ideal," said Dr. Rodriguez.

The researchers also found that the risk for instability increased with a greater number of total surgeries performed on the ipsilateral knee. Varus-valgus constrained polyethylene was used in 70.4 percent of cases, but there was no significant correlation between using varus/valgus constraint and the presence or absence of instability. Constraint is defined as the effect of the elements of knee implant design that provides the stability needed to counteract forces about the knee after arthroplasty, in the presence of a deficient soft-tissue envelope. Determining the amount of constraint necessary can be challenging. Dr. Rodriguez said the study showed that a varus/valgus constraint insert alone may not be sufficient to prevent progressive instability, as the soft tissues stretch following treatment for infection.

"The degree of soft tissue tension that is achieved after treatment for periprosthetic infection at the time of surgery may not represent what it will be afterwards, because of the degree of swelling that exists when you are re-implanting following treatment for infection. After infection, the soft tissue remains swollen and may not give a suitable indication for the use of varus/valgus constraint at that time," said Dr. Rodriguez. "The subjective assessment of soft tissue tension at the time of re-implantation may not be an accurate predictor of stability at one year. We might need a lower threshold to use a hinged prosthesis or plan to stuff the joint tighter than what we might otherwise think ideal."

The study was a collaborative effort among researchers at HSS, Northwell Health/Lenox Hill Hospital, and Columbia University Medical Center. The researchers say that prospective studies with larger sample sizes are needed to shed light on when patients can benefit from increased constraint, such as a hinged prosthesis.

"The key findings of this study are that acute kidney injury happens at a rate which is unexpectedly high and anemia is a predisposing factor," said Jose Rodriguez, MD, a study co-author and an orthopedic surgeon at Hospital for Special Surgery. "In this particular population that is at-risk, we may need to be more vigorous in monitoring for anemia and then treating with a transfusion earlier than we otherwise might have."

PJI is one of the most devastating and frequent complications that can occur after lower extremity joint arthroplasty, such as total knee replacement. The incidence of PJI varies by institution, from about .5 to 4 percent, and often requires revision surgery. Multiple procedures are sometimes necessary to eradicate infection and restore functionality, and even with successful eradication of infection, patients may not achieve optimal functional outcomes.

Mounting evidence suggests that treatment of PJI of the knee with an antibiotic cement spacer may increase the risk for acute kidney injury. "The concept for the study was that when we use a spacer for PJI, we are putting high concentrations of antibiotics in it, usually vancomycin which is renal toxic, in addition to sometimes treating these patients with intravenous vancomycin," said Dr. Rodriguez. "The question we wanted an answer to is what is the incidence of in-hospital acute kidney injury following treatment with an antibiotic spacer?"

To shed light on the issue, the researchers retrospectively identified 75 patients (39 male, 36 female) that received a static or articulating antibiotic cement spacer in New York City from 2007-2017. They collected and analyzed information on patient demographics, comorbidities, dose of antibiotic powder incorporated into the cement spacer, intravenous antibiotics administered, preoperative and postoperative creatinine, blood urea nitrogen and hemoglobin values. Acute kidney injury was defined as a more than 50 percent rise in serum creatinine from preoperative baseline to at least 1.4 mg/dL. A multivariate model was used to control for the demographics of age, gender, body mass index, and baseline creatinine.

The researchers found that in-hospital acute kidney infection occurred in 14.6 percent patients, at an average of 6.3 days (range, 2-8 days). A lower preoperative hemoglobin (OR=.55, P=.015) significantly increased the risk for infection on univariate analysis. Diagnosis of either hypertension or diabetes also showed a strong statistical trend for an increased risk of acute kidney infection (P=.056). When controlling for age (P=.0854), gender (female, P=.404), BMI (P=0.426), and baseline creatinine (P=0.340) on multivariate regression, lower preoperative hemoglobin significantly correlated with a greater percent rise in creatinine postoperatively (B=.304, P=.015).

Anemia is a well-known risk factor for postoperative AKI in patients undergoing cardiopulmonary bypass surgery, and the researchers believe that a lower baseline hemoglobin may be involved in the etiology of AKI in patients undergoing total knee revision. "The major risk factor was a lower hemoglobin level, so anemia predisposes patients to kidney injury, and these patients should receive closer monitoring," said Dr. Rodriguez.

The study was a collaboration among researchers at Lenox Hill Hospital, Monmouth Medical Center, Columbia University Medical Center, and HSS.

"Regardless of the technology that you use, the closer that you can recapitulate that patient's anatomy the better that you will reproduce their kinematics and their function and ultimately the happiness of that knee," said Dr. Rodriguez, referencing data that was presented at the Current Concepts in Joint Replacement Winter Meeting in Orlando, Florida.

"Up until now, the research we have is the first real-time fluoroscopy demonstrating how a custom knee moves relative to most off-the-shelf knees and that shows an improvement. Up until now, we have outcome data that shows that within the first 6 months there is more rapid recovery and more complete recovery in terms of how fast and how smooth the patients move, but it is short term," added Dr. Rodriguez.

Read the full article at healio.com [registration required]. This also appeared in the February 2018 print edition.

"In all the assessments that were made—discontinued walker, discontinued gait aids, opioids, stairs and walking six blocks, there was a marked improvement in the anterior group," said Dr. Rodriguez, referencing recent data during the debate at the Annual Current Concepts in Joint Replacement (CCJR) Winter meeting in Orlando, Florida.

However, while he personally prefers the anterior method when appropriate, he said that both approaches can provide excellent recovery.

"Both of my mentors—Chit Ranawat and Reinhold Ganz taught me you've got to be able to get into the hip every single way," Dr. Rodriguez added.

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