What follows are highlights from these studies:

HSS Study Uses Machine Learning to Predict Risk of Long-Term Pain After Knee Replacement Surgery

A new study led by researchers at HSS used a type of AI known as machine learning (ML) to identify key clinical and biological factors that raise a person’s risk of having persistent pain after total knee arthroplasty (TKA). Risk factors included elevated levels of certain inflammatory cytokines (proteins) in the blood, severe preoperative pain, and a longer period of tourniquet use in the operating room.

“These findings highlight the importance of incorporating biological markers like cytokine levels with patient-specific pain profiles and what the surgeon does during the operation to more accurately predict the risk of long-term pain after surgery,” says Meghan Kirksey, MD, PhD, an anesthesiologist at HSS and senior author of the study.

ML is a specialized approach that uses algorithms and statistical models to analyze patterns in large amounts of data to learn, predict, and make recommendations.

“Machine learning is allowing us to look at patient and clinician information in new ways,” says Alexandra Sideris, PhD, Director of the HSS Pain Prevention Research Center and a coauthor of the study. “It gives us a multidimensional approach to understanding patients’ pain experience that we didn’t have in our arsenal even five or 10 years ago.”

One in five people has significant knee pain months after having TKA, also known as total knee replacement surgery. “The lingering pain greatly affects their daily activities and quality of life, so that’s why it’s an important focus for us,” explains Dr. Sideris.

Persistent postoperative pain (PPP) is typically flagged when a patient has lasting pain at the site of the operation that is above a four on a scale of zero to 10 and severely impacts their activities of daily living three to six months after surgery.

The researchers used four different ML models to analyze data from a previously published study that collected comprehensive clinical information and blood samples from 160 patients before and after TKA at HSS. The new study identified key predictors associated with PPP beyond risk factors that were already known such as sex (women tend to have a higher risk), preexisting pain, and mental health issues like anxiety and depression.

The findings showed that having high blood levels of an inflammatory marker called TARC immediately after surgery raises the risk of PPP. “This molecule hasn’t been extensively studied in pain, but the evidence shows that it was consistently associated with persistent pain six months after surgery across all four ML models we tested,” notes Dr. Kirksey.

Other top predictors of PPP that emerged from the analysis included a higher preoperative pain score at rest, longer tourniquet time (a tourniquet is a device that squeezes the leg to help clear the area of blood flow during surgery), and higher blood levels of other inflammatory cytokines right after surgery.

In this study, researchers entered 318 clinical and biological characteristics collected from patients in the older study and asked each of the ML models to figure out the most important features associated with pain after TKA. The researchers also evaluated the accuracy of the ML models they used and found that XGBoost was the most informative.

“To my knowledge, this is the first study that looked at all of this information and tried to make sense of the best ML approach to use,” says Dr. Sideris. “What is exciting to us is that there was one feature – TARC – that consistently popped up across all four models and it wasn’t on anybody’s radar beforehand…this gives us hope that ML can help us identify with high integrity targets that haven’t been studied before.”

The researchers note that more research is needed to know if their findings can be used to impact clinical care. “Our goal is to be able to use these tools and data to tailor pain management strategies, prevent long-term complications, and personalize treatment decisions,” says Dr. Kirksey.

HSS AI Analysis Reveals What Patients Are Googling About Local Anesthesia

A new study by researchers at HSS used AI to systematically evaluate the types of questions that patients are Googling related to regional (local) anesthesia, identify websites that are frequently presented in search results, and assess the quality of the information provided.

“We knew that patients frequently search for information about anesthesia online, but we wanted to know exactly what they were looking for so that we could proactively address these topics and concerns in our conversations in the clinic and our patient education materials,” says Jashvant Poeran, MD, PhD, Director of Research in the Department of Anesthesiology, Critical Care and Pain Management at HSS and lead author of the study.

The analysis found that most patients’ questions focused on risks, complications, and details surrounding medications, awareness during sedation, nerve block duration, and the recovery process. The study also found that while the overall quality of information accessed during Google searches was accurate, the source of that information was not always clear.

Anesthesiologists see patients in the clinic for a short period to prepare them for surgery and manage expectations.

“There’s so much information being conveyed during that limited time that sometimes patients forget what to ask, or they don’t even know what they should be asking during the visit,” explains Dr. Poeran. “Our study results will help us anticipate some of their questions and give us a starting point when we sit down with them so it’s not so much of a guessing game.”

The researchers entered seven search terms into Google Web Search: “regional nerve block,” “regional anesthesia,” “peripheral nerve block,” “pain block,” “neuraxial anesthesia,” “epidural anesthesia,” and “spinal anesthesia.” The top 200 questions in the “People Also Ask” section and its associated websites were collected, totaling 1,400 question and website combinations.

The authors then used AI to categorize themes and assess website quality. They found that most questions pertained to facts around risks and complications, comparisons between different techniques and approaches, technical details, and indications.

“We were expecting questions around risks and complications, but it was surprising that so many patients were looking at technical details, specifically around sedation,” notes Dr. Poeran. “They were not always aware that you can be awake for a peripheral nerve block, for example.”

Because patients’ questions are linked to specific websites, researchers also wanted to know where patients were being referred to and how reliable the information presented was. The AI analysis found that 55% of websites were academic, 19% were government, and 11% were public/social media sources. Information on government and academic/hospital websites scored the highest in terms of accuracy, and medical practice websites scored the lowest.

Dr. Poeran cautioned that some patients’ questions are nuanced, and online information can bias a person in the wrong direction.

“For example, if you ask whether regional anesthesia is better than general anesthesia you will be able to get generic information about those approaches online, but you need to talk to your doctor to get a more personalized recommendation based on your specific circumstances,” says Dr. Poeran.

While the study revealed important questions, it’s not all-encompassing. “There will be questions that aren’t captured by this study, but anesthesiologists can use this data to guide their consultations with patients scheduled for surgery, provide more-informative patient education materials, and refer them to the most reliable websites for more information,” notes Dr. Poeran.

He plans to continue leveraging AI in his future research endeavors.

“Based on the information we gathered, we will update our educational materials with the questions we now know patients ask most often and may even provide it in different languages and reading levels,” says Dr. Poeran. “We can then use AI to see how that information is perceived and understood by patients, study differences in search terms entered in different languages, etc.”

The first of the three studies, “Aspirin Versus Potent VTE Chemoprophylaxis (VTEC) in Total Knee Arthroplasty: Reduced Postoperative Pain and Complications with Aspirin Use,” examined the experience of total knee arthroplasty (TKA) patients with postoperative pain who were also taking blood thinners. The study included 28,169 patients treated between 2016 and 2023; 18,413 received aspirin while 9,756 received a potent VTE.. Patients were monitored for 90 days following their procedure. The findings suggest that aspirin should be considered the preferred option for reducing postoperative pain in TKA patients.

Patients on more-potent blood thinners tend to experience more pain, swelling and inflammation after surgery, said Brian P. Chalmers, MD, a hip and knee surgeon at HSS and one of the study’s authors. “We have always known that non-steroidal anti-inflammatory medications can improve patients’ swelling and inflammation after surgery. However, the traditional thought and belief has been that we should avoid those in patients on anticoagulation. Our data show there is less risk and less postoperative pain when these patients are utilizing aspirin.”   

A second study, “The Effect of Concomitant Use of Potent Anticoagulation and Anti-Inflammatories on Early Outcomes of Total Hip Arthroplasty,” retrospectively evaluated 5,881 total hip arthroplasty patients who were on anticoagulation. The surgeries were performed between 2016 and 2023; of those patients, 4,867 were concomitantly prescribed NSAIDs and 1,040 received anticoagulation alone. Researchers concluded that the concomitant use of NSAIDs in patients on anticoagulants did not increase the risk of wound-related bleeding complications.

“The conventional thinking has often been that patients on an anticoagulant should not be on an NSAID, that there is going to be bleeding, more risk of wound problems and additional complications. But based on our retrospective data, we did not see increased risk in patients using both anticoagulation and NSAIDs. We did see some additional benefits, including less pain and a somewhat easier recovery,” Dr. Chalmers stated. “NSAIDs appear to be safe in this setting and may help decrease postoperative pain and reduce opioid use following surgery.”

The final study, “Cefazolin and the R-1 Side Chain: Why Your Joint Arthroplasty Patients With Cephalosporin Allergy Can Safely Be Given Cefazolin,” assessed the safety and effectiveness of the antibiotic Cefazolin in patients with documented cephalosporin allergies. This is the first study to evaluate these questions.

From 2016 to 2024, researchers compared patients with a reported cephalosporin allergy who received perioperative cefazolin with those who received alternative antibiotic prophylaxis. This study included 89,993 hip and knee arthroplasty patients. Of these, 1,267 had a documented allergy. The study resulted in zero incidence of IgE-mediated or “severe” type IV allergic reactions, concluding that cefazolin can be safely administered to most patients with an existing cephalosporin allergy.

“When patients have a mild allergic reaction, there is often a reflex to give them another antibiotic in a different family of drugs. However, alternative options aren’t always as effective,” said Matthew S. Austin, MD, hip and knee surgeon at HSS and a study author. “Clear protocols should be put in place to guide decision-making when managing these types of allergies.”

These findings underscore HSS’s ongoing commitment to challenging conventional assumptions and using data-driven research to refine perioperative care. The studies highlight how targeted medication strategies can improve safety, reduce complications and enhance outcomes for patients undergoing hip and knee arthroplasty.

Study Details 

“Aspirin Versus Potent VTE Chemoprophylaxis in Total Knee Arthroplasty: Reduced Postoperative Pain and Complications with Aspirin Use”

 Alex Anatone, Alexis Gabriel Gonzalez, Richard Hwang, David Andrew Kolin, Aaron Ira Weinblatt, Amar S Ranawat, Alejandro Gonzalez Della Valle, Brian Chalmers

“The Effect of Concomitant Use of Potent Anticoagulation and Anti-Inflammatories on Early Outcomes of Total Hip Arthroplasty”

Alexis Gabriel Gonzalez, Aaron Ira Weinblatt, Agnes Cororaton Jones, Stephen Lyman, Richard Hwang, Alex Anatone, Carlo Marega, Alejandro Gonzalez Della Valle, Brian Chalmers

“Cefazolin and the R-1 Side Chain: Why Your Joint Arthroplasty Patients With Cephalosporin Allergy Can Safely Be Given Cefazolin”

Josef Jolissaint, Katherine E Mallett, Andrew Thomson, Alberto V Carli, Matthew Austin

First introduced in the late 1800’s, the procedure, called knee osteotomy, involves cutting and reshaping the shinbone or thighbone to relieve pressure on the knee joint. It was initially used as a common treatment for arthritis and later for various orthopedic conditions and injuries, but it became less popular with the advent of the modern knee replacement in the 1970s. Nevertheless, surgeons continued to use and refine the technique. Today, the approach is used to fix bowleg deformity and prevent the need for knee replacement surgery, which carries a higher risk of complications particularly in people under age 50.  

Bowleg deformity is an incorrect alignment around the knee that can affect people of all ages. The many causes of bowleg syndrome range from illnesses such as Blount’s disease to improperly healed fractures and vitamin deficiencies.

Patients who had knee osteotomy reported positive outcomes and significant improvements in quality of life, according to a comprehensive review of the literature on the technique that was led by Anil S, Ranawat, MD, Chief of the Hip and Knee Division of the Sports Medicine Institute at Hospital for Special Surgery (HSS). High patient satisfaction rates included less pain, better movement, and very few complications after the surgery, which helped delay or avoid the need for knee replacement in the vast majority of cases. The results are being presented at the AOSSM annual meeting.

“The development of new technologies, such as digital software planning, advanced CT imaging, and other patient-specific tools, is enabling us to resolve patients’ knee pain and preserve their knee function for a longer period of time,” explains Dr. Ranawat. “This modern evolution of an old operation has helped us tailor these procedures so that they are done in the safest, most precise way possible.”

Osteotomy is no longer a one-size-fits-all approach. “These improved outcomes were made possible by the advent of patient-specific instrumentation (PSI), in which a surgeon uses a patient’s CT scan and digital software to do a virtual surgery and plan the ideal operation tailored to the individual’s anatomy and needs,” explains Dr. Ranawat, an expert in joint restoration and preservation.

The development of knee replacement surgery in the 1970s caused surgeons to recommend knee osteotomy less frequently, however younger patients under age 50 tended not to do well with it due to high rates of infection and other complications. In addition, knee replacements have a life span of about 15 to 20 years, so younger patients often need a second operation when their knees fail.

“New patient-specific technologies have revolutionized the safety and precision of osteotomy, even more than knee replacement, so now if we do an osteotomy on a 25- or 30-year-old, the operation could last 40 years,” says Dr. Ranawat. “This is why joint preservation has been our goal at HSS over the last two decades. We are taking a much more proactive approach to offering knee osteotomy in younger patients to ideally avoid knee replacement altogether.”

HSS has been a thought leader in knee osteotomy for many years and is using all different forms of modern technology to improve surgical precision and patient outcomes. Dr. Ranawat and his colleagues will continue to build on the benefits of PSI, integrating the latest tools and technology to redefine joint preservation.

“We want our younger patients to know they don’t have to live with pain or rush into a knee replacement,” said Dr. Ranawat. “This is about preserving function and quality of life for the long haul. Incorporating artificial intelligence, machine learning, and advanced imaging will lead to smarter PSI systems​ and open the door to robotic-assisted surgeries that could revolutionize knee osteotomy in the future,” he says.

“It is an honor to have one of the top professional organizations in the field of regional anesthesia and pain medicine highlight the collaborative work of our department's Pain Prevention Research Center,” said Alexandra Sideris, PhD, director of the Pain Prevention Research Center at HSS. “The award reflects our dedication to innovations in patient care and underscores the greater scientific community's acknowledgement of our efforts.” 

More than one million people undergo knee replacement surgery each year in the United States, and those numbers continue to rise, Dr. Sideris notes. “There is a need to better understand patients’ individual pain trajectories, and one of the most exciting approaches is to leverage artificial intelligence. With our huge patient database at HSS, machine learning can analyze factors such as age, gender, BMI, and presurgical pain levels to predict which patients are at greater risk of severe pain after surgery,” she said. Armed with this information, the care team can tailor personalized pain management plans to meet patients’ needs. 

The HSS researchers had several goals: utilize machine learning to identify pain archetypes following total knee replacement; determine important features for predicting pain outcomes; and classify patients at risk of severe pain in the immediate postoperative period. The retrospective study included 17,200 patients who had total knee replacements at HSS from April 1, 2021, to October 31, 2024. 

“Using unsupervised machine learning, we identified two distinct pain archetypes in patients who underwent total knee replacement, which corresponded to those who experienced severe, difficult to control pain after surgery and those whose pain was relatively well controlled,” explained Justin Chew, MD, PhD, a clinical fellow at HSS who presented the study at the ASRA meeting on May 1. “We then utilized supervised machine learning to determine the most significant predictive factors for severe pain. In our study, risk factors included younger age, greater physical/mental impairment, higher BMI, and preoperative opioid or gabapentinoid use.” 

Dr. Sideris notes that ongoing and future studies at HSS will continue to leverage AI with the goal of improving patient outcomes. While the award-winning study focused on the immediate postoperative period, she said additional studies will follow patients’ pain trajectory and recovery over longer periods of time to determine which strategies doctors can employ before surgery, intraoperatively and in the immediate postoperative period to manage pain in high-risk patients. 

Reference: 
Classification and stratification of patient pain archetypes following total knee arthroplasty: a machine learning approach 
Justin Chew, MD, PhD, Junying Wang, Alexandra Sideris, PhD, Victoria Xu, Daniel Maalouf, MD, MPH, Stavros Memtsoudis, MD, PhD, MBA, Jashvant Poeran, MD, PhD, Jiabin Liu, MD, PhD. 

“As an increasing number of younger adults in their 40s and 50s consider total knee replacement, many wonder how long knee implants last before requiring a revision procedure,” says William J. Long, MD, FRCSC, an HSS hip and knee surgeon and the senior author of the study. “The findings from our study—the largest and longest follow-up of patients under 55 undergoing total knee replacement—confirm that young patients can be confident their initial knee implants will allow them to pursue a high level of activity and more than likely last the rest of their lives.”

HSS orthopedic surgeons designed the longitudinal study to track outcomes for patients 55 years of age and younger who had total knee replacements between 1977 and 1992. During that period, they used knee prostheses known as the Insall-Burstein I and Insall-Burstein II—predecessors of implants used today that provide posterior stability. Both designs were conceived and developed at HSS. Previously, the investigators conducted patient follow-ups at 10, 25, and 30 years following surgery.

For this final report, Dr. Long and colleagues analyzed outcomes after 40 years for 81 patients aged 33 to 55 years. The analysis included 107 knees in total. Overall, 70% of patients in the study had no revision procedures in their lifetime. Patients were three to four times more likely to have passed away after 40 years than to have required a revision. Remarkably, among the 49 patients who received the original Insall-Burstein I prostheses, 80% did not have any revision surgeries.

“Considering that today's knee replacements have addressed the pitfalls leading to the majority of revisions for mechanical issues in Insall-Burstein I and Insall-Burstein II implants, these are very reassuring findings," says Dr. Long.

Dr. Long also examined six patients (eight knees) in person, and lead and presenting author Aaron Weinblatt, BA, contacted many more patients by phone. There were no signs of loosening nor were there any changes in symmetry or alignment of the original components. Additionally, patients reported an ongoing improved level of activity after surgery.

This was supported by patient-reported activity data collected for eight patients (10 knees) and measured using the Tegner Activity Scale (TAS). Before undergoing total knee replacement, the average TAS score was only 1.5, indicating they could work in a sedentary job and walk on uneven ground but not hike or backpack. At 40 years, their average TAS score was 2.7, indicating the ability to work in light labor occupations and participate in recreational activities such as swimming and walking in forests.

“Patients requiring a total knee replacement should not delay having surgery,” Dr. Long says. “Our study results highlight that those who undergo knee replacement sooner are more likely to maintain a high level of activity that contributes to a healthy, longer-term lifespan.”

Dr. Long adds that a previous HSS study published in 2014 at the 30-year follow-up showed that for the small percentage of patients who required revisions, the vast majority were doing well, with an average TAS score of 3.0, a good range of motion and no signs of loosening. ²

Authors: Aaron I. Weinblatt, BA, Victoria E. Bergstein, BA, Walter L. Taylor, MPhil, BS, Stephen Lyman, PhD, Felix C. Oettl, MD, W. Norman Scott, MD, FAAOS, William J. Long, MD, FRCSC.

Reference:

¹ Weinblatt AI, Bergstein VE, Taylor WL, Lyman S, Oettl FC, Scott WN, Long WJ. Total knee replacement in young, active patients: long-term follow-up and functional outcome: A final follow-up of previous report. Accessed February 10, 2025, at https://submissions.mirasmart.com/AAOS2025/Itinerary/PresentationDetail.aspx?evdid=2532

² Long WJ, Bryce CD, Hollenbeak CS, Benner RW, Scott WN. Total knee replacement in young, active patients: long-term follow-up and functional outcome: a concise follow-up of a previous report. J Bone Joint Surg Am. 2014 Sep 17;96(18):e159. Accessed February 19, 2025, at  https://pubmed.ncbi.nlm.nih.gov/25232089/  

What follows are highlights from these studies:

Limiting Use of Tourniquets During Knee Replacement Surgery Improves Patient Outcomes

Tourniquets have traditionally been used during TKA to reduce blood loss and the need for transfusions. However, a new study of almost 18,000 patients from 2019 to 2023 found that prolonged tourniquet use was linked to increased pain, higher opioid use, and a longer recovery. 

“We found that limiting tourniquet use was associated with slightly lower rates of opioid use to control pain after surgery and a quicker ability to complete physical therapy and leave the hospital,” said Brian P. Chalmers, MD, hip and knee surgeon at HSS and co-senior author of the study.

Thanks to advances in medicine and technology, tourniquets may not be needed as often. For example, tranexamic acid (TXA) is now commonly used to effectively reduce bleeding and lower the likelihood of patients requiring a blood transfusion.

“If you have a drug that has this beneficial effect, then the need for a tourniquet may be reduced,” explained Alejandro Gonzalez Della Valle, MD, hip and knee surgeon at HSS and co-senior author of the research. “If you limit tourniquet use, patients will hurt less and will move sooner, and that will allow patients to go home sometimes the same day.” 

Dr. Della Valle notes that limiting tourniquet use can also reduce opioid consumption. The reason that tourniquet use during TKA has been associated with increased post-operative pain is because the device compresses the quadricep and hamstring muscles to restrict blood flow during the operation. The increased pain may impact the time it takes to complete rehabilitation.

Surgeons have also traditionally used tourniquets to keep the area between the knee implant and the bone as dry as possible, which helps bone cement create a stronger bond between the bone and the implant, potentially reducing the risk of loosening over time.

“Recent studies have shown that you can obtain a dry field without using a tourniquet, reducing its necessity during TKA,” explained Dr. Chalmers.  

Another development that has lessened the need for the use of tourniquets is cementless fixation, in which a specially-designed implant that allows the bone to grow into the implant and achieve long-term fixation without the use of cement.

There is currently no consensus in the literature or among surgeons throughout the country on the use of tourniquets during TKA. Surgeons use these devices differently based on individual patient needs. Some use a tourniquet from the time of incision until the implant is fixated to the bone, while others use it only during cementation or throughout the entire procedure until the wound is closed and the dressings are in place. Some surgeons may opt not to use a tourniquet at all. 

“What sets this study apart is that it captures what surgeons are doing in their daily practice,” said Dr. Chalmers. “To our knowledge, this is the only paper that addresses several different ways surgeons use tourniquets during TKA, including no usage, limited usage, and full usage.”

The study’s authors conclude that reduced tourniquet use should be considered within the realm of multiple advances that help patients recover faster after surgery and with less pain. These include newer drugs and tools used to reduce pain and blood loss during surgery, two major factors that often prolong hospital stays.

“Any measures we can take around the time of surgery to help those factors can significantly improve patient outcomes,” said Dr. Della Valle.

NSAIDs Reduce Risk of Fibrosis Needing Further Treatment after Knee Replacement Surgery

A new study led by surgeons at HSS shows that patients who were prescribed a non-steroidal anti-inflammatory drug (NSAID) after TKA had a reduced risk of developing painful scar tissue, a condition known as arthrofibrosis, which often requires additional procedures. The findings also shed light on the durations for NSAID use to prevent fibrosis following surgery.

In arthrofibrosis, excessive scar tissue forms in and around a joint after an operation. It can lead to stiffness, pain and reduced range of motion in the joint. Approximately 2% to 6% of patients require a minimally invasive procedure called manipulation under anesthesia (MUA) to treat this complication.

The researchers found that patients who were prescribed an NSAID had a significantly lower incidence of MUAs (5.3%) 90 days after surgery compared to those who did not have an NSAID prescription (12.6%). The study included more than 23,000 people who had TKA at HSS between 2017 and 2021.

“This study highlights the importance of NSAID use for early recovery after TKA,” says Peter K. Sculco, MD, hip and knee surgeon at HSS and senior author of the study. “These medications are associated with lower rates of fibrotic pain and stiffness requiring an intervention such as MUA.”

He added that decreased risk was not seen in patients who used NSAIDs for more than four weeks, suggesting patients stop within one month’s time to get the most benefit.

Some patients, however, cannot use NSAID medications due to risk of bleeding or gastrointestinal or kidney issues.

“We now use steroids for one week after TKA in patients who are unable to take NSAIDs,” explained Dr. Sculco. “However, further research is necessary to determine the effect of steroids on MUA rates and the appropriate dose and duration for this group of patients.”

Local Anesthetic Leads to Better Patient Outcomes after Revision Knee Replacement Surgery

A new study led by surgeons at HSS found that the use of a new local anesthetic at the time of revision TKA enabled patients to leave the hospital sooner and recover faster.

According to the findings, a recently introduced pain medication known as extended-release, dual-acting local anesthetic (ERDALA) used at the time of aseptic revision TKA was associated with better patient outcomes. These included completing physical therapy sooner, shorter hospital stays, and more patients being discharged within one day after surgery.

Approximately 5% to 10% of patients need aseptic revision TKA, a surgical procedure done to address loosening, stiffness, or instability of a non-infected knee joint that was previously replaced with TKA.

The study reviewed outcomes of 171 patients who had aseptic revision TKA at HSS between January 2021 and May 2023. Patients either received ERDALA (51.5%) or standard of care periarticular injections (PAI) (48.5%) during surgery. The researchers found that patients who received ERDALA went home nearly a day sooner and cleared physical therapy approximately 20 hours faster than those who received PAI.

“ERDALA did not reduce pain scores or the total amount of opioids prescribed in this study but was associated with helping patients reach early recovery milestones sooner,” noted Dr. Peter Sculco, who is also senior author of this study. “This medication can be a valuable tool in rapid recovery strategies used in aseptic revision TKA, which can lead to patients walking better and getting home faster.”

He added that further research is needed to explore these strategies in the revision population, especially as more revision surgeries are performed in the outpatient setting.

“These findings give some reassurance to female patients that there are physiological reasons why they are having more pain,” says Bella Mehta, MBBS, MS, rheumatologist at HSS and lead author of the study. “Our work may also help us develop better therapies, especially for women with more severe symptoms.”

The study enrolled 135 patients with knee OA who were scheduled to have total knee replacement. A total of 82 participants were female. Researchers analyzed patient-reported symptoms of pain, histology (tissue samples removed during surgery and examined under the microscope) and genetic markers of inflammation in the blood.

The study found that women with knee OA had higher markers of inflammation in their blood, increased tissue inflammation and widespread cartilage loss. This corresponds with the study’s findings that women reported higher levels of pain, even at night when at rest.

The findings also revealed specific genetic expression patterns in women that notably increased synovial tissue inflammation. This occurs when the synovium, the thin layer of tissue above the cartilage that helps lubricate the knee joint, becomes inflamed and painful.

“Traditionally, it was thought that knee osteoarthritis was caused by years of significant wear and tear on the cartilage in the knee joint, but synovial inflammation is now known to play a big role in this condition,” notes Dr. Mehta.

Knee osteoarthritis is the most common type of arthritis in the world. Most people over the age of 65 have some form of it, with around 70% to 80% experiencing symptoms of pain and stiffness.

Pain is typically reported more frequently in women with knee OA than in men. Dr. Mehta suggests several theories as to why, including:

-Mechanical differences between men and women. A woman’s pelvis or hip bone is shaped differently than men so they can accommodate having babies. This has implications on the knee joint, which may increase osteoarthritis and pain.

-Hormonal differences in estrogen and progesterone after menopause, which may make women more prone to osteoarthritis.

-Differences in genetics. Women are born with two X chromosomes, whereas men have an X and a Y chromosome. The second X chromosome expresses certain genes that increase the likelihood for women to have osteoarthritis.

“It’s not that women complain of more pain. There are objective, physiological differences that we have seen between men and women that can explain this,” says Dr. Mehta. “For example, they have increased markers of inflammation in their blood, inflammatory gene expression and more mechanical stress and cartilage loss in the knee, all contributing to more pain even at rest.”

Currently, first-line treatments for people with knee OA include medications to manage pain, and exercise to strengthen the muscles and ligaments around the knees. However, if there is no improvement, surgery is recommended.

Researchers continue to look for ways to improve treatment options for knee OA. “There may be certain immunomodulatory agents that target the genetic mechanisms driving tissue inflammation in women, but more research is needed to better understand these genes and their role in accelerating knee osteoarthritis in females,” says Dr. Mehta.  

Advancements in surgical techniques and the increased use of a medication called tranexamic acid for preventing and controlling bleeding have made it possible for many patients undergoing knee replacement to avoid needing a transfusion, which requires hospital admission for at least a day.

Despite these advancements, it was believed that patients with RA undergoing orthopedic surgeries had an elevated risk of transfusion since they tend to have higher rates of anemia compared to the individuals without the disease. RA occurs in about 1% of the general American population.² About 4% of patients having joint replacement surgeries at HSS have the disease.

“Learning that rheumatoid arthritis was not a transfusion risk factor was unexpected,” said HSS rheumatologist Susan M. Goodman, MD, co-author of the study. “However, we believe presurgical care, including proactively managing chronic anemia before surgery, played a key role in minimizing transfusion risk.”

For their study, Dr. Goodman, HSS rheumatologist Linda A. Russell, MD, and colleagues analyzed hospital records for more than 29,000 patients who had a single total knee arthroplasty procedure at HSS from February 2016 to December 2022. A total of 822 patients, or 2.8%, received transfusions. The transfusion rate declined significantly during the study period from 5.7% in 2016 to 0.9% in 2022.

The investigators reviewed patient demographics such as age and sex, preoperative hemoglobin levels, RA diagnosis and the use of tranexamic acid during surgery, and then looked for associations with transfusion risk.

“In addition to finding that rheumatoid arthritis was not a transfusion risk factor, analysis revealed that a higher preoperative hemoglobin level and the use of tranexamic acid significantly decreased transfusion risk, while being male and having a greater burden of other diseases increased risk,” said HSS pre-doctoral student and research assistant Stephen Batter, BA, the presenting author of the poster summarizing the study.

The research team plans to use their unexpected findings to develop a tool to identify patients with different levels of transfusion risk based on preoperative hemoglobin level, sex, age and health status. This initiative may help orthopedic surgeons better anticipate which patients can safely avoid transfusion and may be suitable candidates for outpatient knee replacement surgery.

Authors: Stephen Batter, BA, Huong Do, MA, Dongmei Sun, PhD, Ahmed Deeb, BA, Trang Bui, MD, Jason L. Blevins, MD, Mark P. Figgie, MD, Gwo-Chin Lee, MD, J. Alex B. Gibbons, BA, Bella Mehta, MD, MS, MBBS, Susan M. Goodman, MD, Linda Russell, MD.

Reference:

¹ Batter S, Do H, Sun D, Deeb A, Bui T, Blevins J, Figgie M, Lee G, Gibbons J, Mehta B, Goodman S, A Russell L. Investigating Predictors of Transfusion in Rheumatoid Arthritis and Osteoarthritis Patients Undergoing Knee Arthroplasty [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/investigating-predictors-of-transfusion-in-rheumatoid-arthritis-and-osteoarthritis-patients-undergoing-knee-arthroplasty/. Accessed October 10, 2024.

² Xu Y, Wu Q. Prevalence Trend and Disparities in Rheumatoid Arthritis among US Adults, 2005-2018. J Clin Med. 2021;10(15):3289. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348893/. Accessed October 10, 2024.

“We have found that robotic assistance leads to improved implant positioning, alignment and ligament balance, which enable us to better replicate the patient’s natural anatomy,” said David J. Mayman, MD, chief of the Adult Reconstruction and Joint Replacement Service at HSS. “With our vast registry of patient data and strong commitment to research, HSS is in a unique position to continue leading the evolution of robotic assistance in the operating room.”

The first study found that the use of a surgical robot during total knee replacement surgery reduced the need for manipulation under anesthesia (MUA), an outpatient procedure that may be prescribed when physical therapy (PT) after surgery becomes too painful for the patient due to joint stiffness caused by scar tissue. During the course of care, approximately 3.5% of knee replacement patients undergo MUA, according to Seth A. Jerabek, MD, hip and knee surgeon at HSS and co-author of this study, typically within 90 days of their surgery. After MUA, patients are typically better able to participate in PT and progress in their recovery.

Investigators at HSS set out to determine if the use of computer navigation or robotic-arm assistance during surgery reduced the need for MUA. Previous studies have shown that the use of either tool leads to a more precise knee replacement.

The HSS researchers conducted a retrospective chart review of 21,893 knee replacement surgeries performed between April 2008 and December 2022. They found that the use of the robotic arm or computer navigation led to a significant decrease in the number of patients who needed MUA after surgery (2.7% of patients with robotic-assisted surgery; 2.8% of patients whose surgery was performed with computer navigation; 3.7% of patients whose surgery was performed without either technology).

“These results highlight the potential benefits of incorporating technological advancements into knee replacement surgery, offering improved outcomes and reducing the need for additional interventions such as MUA,” Dr. Jerabek said.

The second study compared short-term outcomes of the anterior versus the posterior approach in robotic-assisted total hip replacement (THR) surgery. “There is no consensus on which approach has a lower risk of postoperative complications,” said Elizabeth B.  Gausden, MD, MPH, a hip and knee surgeon at HSS and principal investigator of the study. “This can often lead to confusion on the part of the patient as to which approach may be best for them. Our objective was to compare rates of dislocation, re-operation, revision and patient-reported outcome measures of each approach performed with robotic assistance.”

Dr. Gausden and colleagues identified 2,040 consecutive robotic-assisted THRs for osteoarthritis in the HSS patient registry between 2017 and 2020. A total of 497 hip replacements were performed using the anterior approach; 1,542 were performed with the posterior approach.

At mean follow-up of 18 months, the researchers found no difference in the rate of dislocation, re-operation or revision surgery between the two approaches. At early follow-up of six weeks, the anterior approach was associated with a somewhat faster functional recovery. By 3 months following the THA, there were no longer significant differences between patients who had different approaches. “The take-home message is that hip replacement has excellent outcomes with each respective approach when performed by surgeons with extensive experience in that approach,” Dr. Gausden said. “While the goal of the study was not to compare robotic THA to manual THA, it is likely that the very low incidence of instability or dislocation overall can be attributed to the use of robotic technology for planning and execution.”

"As the use of robotic assistance in joint replacement surgery becomes more common, future studies should evaluate outcomes over longer periods of time,” concluded Dr. Mayman. “As a leader in the use of this technology, HSS continues to study various robotic systems to acquire the data needed to provide the evidence-based care that will benefit our patients.”  

References:

Robotic-assisted Total Knee Arthroplasty Is Associated with Decreased Manipulation under Anesthesia Compared to Manual Approach

Authors: Cale Pagan; David J. Mayman, MD; Douglas E. Padgett, MD; Jonathan M. Vigdorchik, MD; Peter K. Sculco, MD; Seth A. Jerabek, MD; Theofilos Karasavvidis, MD (HSS).

Program Number: P153 – February 14, 2024

Comparison of Short-Term Outcomes Between Direct Anterior and Posterolateral Approach in Robotic-Assisted Total Hip Arthroplasty

Authors: Nikhil Vasireddi, MHA (Case Western); Sonia Chandi, MD; Colin Neitzke; Agnes Cororaton, MS; Jason L. Blevins, MD; Jonathan M. Vigdorchik, MD; Alexander S. McLawhorn, MD, MBA; Elizabeth B. Gausden, MD, MPH (HSS).

Program Number: e076 – February 12, 2024

Research highlights include the evaluation of artificial intelligence (AI) chatbots to provide accurate answers to medical questions about spine surgery, and two retrospective studies analyzing outcomes in both knee and hip replacement surgeries performed with robotic assistance. 

HSS Research Evaluates Whether AI Chatbots Provide Reliable Medical Information

A study co-authored by Sheeraz Qureshi, MD, MBA, co-chief of HSS Spine and colleagues identified nine frequently asked questions about cervical spine surgery, which they considered to be of particular clinical relevance. Question topics ranged from the benefits and drawbacks of different surgical approaches to side effects and recovery after surgery. The questions were inputted one at a time into ChatGPT version 3.5. Two experts in cervical spine surgery who were not involved in designing the questions rated the chatbot’s responses on accuracy, appropriateness, and readability. On average, the responses received a score of 8.1/10, with a 3.9/5 for accuracy and a 2.2/3 for appropriateness. The main drawback the reviewers noted was that ChatGPT failed to provide comprehensive responses, often omitting important factors. AI chatbots are more accurate than expected when asked to answer medical questions about spine surgery, however patients still need to use extreme caution when turning to these tools for help with medical decision-making.

New HSS Studies Highlight the Benefits of Robotic-Assisted Joint Replacement Surgery

HSS investigators presented two retrospective studies analyzing outcomes in both knee and hip replacement surgeries performed with robotic assistance.

The first study co-authored by HSS hip and knee surgeon Seth A. Jerabek, MD, and colleagues found that the use of a surgical robot during total knee replacement surgery reduced the need for manipulation under anesthesia, an outpatient procedure that may be prescribed when physical therapy after surgery becomes too painful for the patient due to joint stiffness caused by scar tissue.

The second study led by HSS hip and knee surgeon Elizabeth B.  Gausden, MD, MPH and colleagues compared short-term outcomes (e.g., rates of dislocation, re-operation, revision, and patient-reported outcome measures) of the anterior versus the posterior approach in robotic-assisted total hip replacement surgery. The investigators found that hip replacement has excellent outcomes with each respective approach when performed by surgeons with extensive experience in that approach. Additionally, it is likely that the very low incidence of instability or dislocation overall can be attributed to the use of robotic technology for planning and execution.

“There’s been considerable research and effort into reducing opioid consumption after elective surgeries, and specifically after knee replacement. Many people consider knee replacements the most painful elective surgery someone can have,” says Dr. Ast. “We’ve done a lot of great work, and we’ve already cut the amount of opioids that patients take by approximately 75% as compared to 10 years ago. But there’s still room to go, which is why we want to focus on developing novel forms of non-opioid pain medication.”

Ketamine is a well understood drug that has been approved by the US Food and Drug Administration for postoperative pain management, but it is currently only administered intravenously in the inpatient setting. A noteworthy feature of the new formulation evaluated in this study was that it was an oral medication. “Our goal was to find an effective medication that patients could take home with them,” explains Dr. Ast. “This is especially important because the average stay after total knee replacement surgery is only 24 hours, but we know that the worst postsurgical pain arises between days 3 and 10.”

Oral ketamine is already being studied as a safe alternative to opioids but has low bioavailability in its isolated form. Additionally, there are concerns about ketamine being abused, due to the feelings of dissociation that it creates. The ketamine used in this study was specially formulated for oral use and is manufactured in a way that potentially limits its ability be abused by melting or crushing.  “We’ve learned through basic science studies that nonsteroidal anti-inflammatories like aspirin can buffer the effects of other drugs by adjusting the pH. Aspirin and ketamine work together synergistically on the body’s pain receptors,” says Dr. Ast. “This allows you to use relatively low doses of the ketamine, which also aids in preventing the dissociative feelings even at larger doses.”

The trial enrolled 22 men and women between the ages of 47 and 81 who were undergoing elective total knee replacement. The criteria for enrollment were tightly controlled, including being generally in good health and having no history of opioid use. All the study participants received an oral dose of aspirin and ketamine four times a day until discharge (up to 72 hours) and were monitored for the duration of the study, including being assessed for pain using standard pain scales.

“At HSS, nothing matters more than patient safety,” Dr. Ast says. “That’s why it was so important to do this pilot study with a small number of patients who were closely followed for the entirety of their treatment before developing a larger trial.” Overall, 18 of the 22 patients reported no side effects at all from the treatment. Two of them reported feelings of dizziness. Two others withdrew from the study early because they felt they needed more pain relief.

“If this treatment proves to be as effective as we hope it’s going to be, we can imagine a world where — even after something as painful as knee replacement surgery — patients go home with only a few opioid pills to take if needed, rather than a more typical amount of 25 or 30 pills that are often provided today,” Dr. Ast says. “This could dramatically reduce the number of opioid pills that end up out on the streets every year, just from this one procedure.”

For Dr. Ast, the quest to find alternatives to opioids is personal: “Unfortunately, I grew up in an area that has been hit hard by the opioid epidemic and have seen people I knew pass away from opioid overdoses,” he says. “That’s one of the main reasons the focus of my research for the past 10 years has been on finding new forms of pain medication that can minimize opioid use and ultimately be developed and commercialized.”

A manuscript of this study is in preparation for presentation and publication. The next phase clinical trial is expected to begin at HSS in the near future.

Researchers at HSS and other institutions have noted that women with knee osteoarthritis report more pain than men, but the reason for this difference has been unclear. “Others have speculated that women tend to delay surgery more than men, but when we looked in our database, that wasn’t true,” said HSS rheumatologist Dana Orange, MD, MS, assistant professor at The Rockefeller University and senior author of the study. “We studied synovial tissue removed at the time of total knee arthroplasty to look for a biological reason that may explain the difference in reported pain between sexes.”  

Synovial tissue lines the knee joint and produces fluid that helps the joint move. It can become inflamed as osteoarthritis progresses. Pathologists at HSS have been generating data on different types of cells found in synovial tissue, including mast cells, which are also found in many other tissues throughout the body and are commonly known for producing inflammatory chemicals called histamines during allergic reactions and asthma. Basic research by other scientists has suggested a link between mast cells and osteoarthritis progression and pain.

Dr. Orange and colleagues, including HSS rheumatologist Bella Mehta, MBBS, MS, lead author of the study, studied joint tissue obtained from 96 women and 61 men who underwent total knee replacement at HSS. They counted the number of cells for more than a dozen cell types typically found in synovial tissue and examined synovial fluid and blood using a high-powered microscope. They also evaluated patient-reported pain outcomes collected with two validated surveys. “At HSS, we were in a unique position to conduct this research because we have synovial tissues collected from patients with end-stage osteoarthritis undergoing arthroplasty and expert musculoskeletal pathologists who systematically grade tissue samples for 13 characteristics,” Dr. Mehta said.  

The investigators discovered that synovial tissue from women had significantly more mast cells, 63 per sample area, compared to 46 in tissue from men, on average. They also found higher levels of a byproduct of mast cells called tryptase in synovial tissue from women than men, providing further evidence of increased mast cell activity. No other differences in synovial tissue between sexes were observed. Finally, as expected, women reported worse pain than men on both surveys.

“We hope our findings encourage other researchers to start thinking about biological factors that may contribute to sex differences in patient-reported pain in knee osteoarthritis,” Dr. Orange said.

Authors: Bella Mehta, MBBS, MS, Edward F. Dicarlo, MD, Miguel Otero, PhD, Peter K. Sculco, MD, Mark P. Figgie, MD, Susan M. Goodman, MD (HSS), Fei Wang, PhD (Weill Cornell Medicine), Eun Kyung Song, PhD (Stanford University School of Medicine), Dana Orange, MD, MS (HSS and The Rockefeller University).