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.

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). 

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

 Three studies focus on how to optimize total knee arthroplasty (TKA) surgery using biomechanics and computer modeling, while another study discusses how three-dimensional (3-D) modeling can improve total hip arthroplasty (THA).

 What follows are some highlights from the meeting:

Undersizing Tibial Baseplates in Cementless TKA Has Negative but Small Impact for Bone–Implant Interaction: A Computational Biomechanical Study

Computational biomechanical modeling is useful for taking a closer look at how making changes to orthopedic surgery techniques affects patient outcomes. A study led by Fernando J. Quevedo-González, PhD, assistant scientist in the Department of Biomechanics at HSS, and HSS hip and knee surgeon Jonathan M. Vigdorchik, MD, used these kinds of models to determine how best to minimize the risk of complications in cementless TKA. The model was developed using preoperative scans from 12 female patients about to undergo robotic TKA and was used to ask questions about how sizing the tibial baseplate (the metal part of the prosthesis that connects to the shin bone) affects outcomes. The investigators found that, in general, decreasing the size of the baseplate increased the amount of bone at risk of failure, but this risk was small compared with normal variability of bone quality among patients and how their individual knee joints were loaded as they used their knee in performing activities of daily living. Based on this result, they concluded that baseplate undersizing can be done to optimize the placement of the tibial component of the TKA without increasing the risk of bone failure.

Authors: Fernando J. Quevedo-González, PhD, Peter K. Sculco, MD, Cynthia Kahlenberg, MD, Joseph D. Lipman, MS, Timothy M. Wright, PhD, Jonathan M. Vigdorchik, MD.

Posterior Tibial Slope in Total Knee Arthroplasty: The Transmalleolar Sagittal Axis Underestimates Slope Compared to Traditional Intramedullary Axis

The tibial slope, one of multiple angles used to place a TKA, defines how the tibial component meets the knee and impacts the knee’s ability to bend and the strain that’s put on the ligaments throughout range of motion. A study led by HSS hip and knee surgeons Brian P. Chalmers, MD, and Steven B. Haas, MD, looked at how robotics and computer navigation influence the tibial slope in TKA. Historically, knee implants were designed using what is called the intramedullary axis to measure the tibial slope, but technology-assisted knee replacement operations determine the slope in a different way. The investigators retrospectively reviewed preoperative CT scans from 40 TKA procedures and reconstructed the 3-D geometry of the tibia and fibula to determine the slope based on the intramedullary axis. They determined that in many cases, the alternate calculation of the slope used in technology-assisted procedures resulted in a different slope in the newly implanted knee. This difference could have a negative effect on the knee’s movement and mechanics, suggesting that as more procedures are performed using robotic-assisted technology, the need to re-think implant designs to incorporate these changes is likely.

Authors: Brian P. Chalmers, MD, Fernando J. Quevedo-González, PhD, Michael P. Ast, MD, Steven B. Haas, MD.

The Initial Fixation of Cementless TKA Is Associated with the AP Translation During Gait: A Computational Study

The two main goals of TKA surgery are restoring the motion of the knee joint to as close to a native knee as possible, and ensuring that the implant is properly attached to the bone so that it lasts as long as possible and does not loosen. A novel study led by Jonathan Glenday, PhD, a postdoctoral fellow, and Fernando J. Quevedo-González, PhD, assistant scientist, both in the Department of Biomechanics at HSS, looked at the intricate relationship between attachment to the bone and joint motion, and how these two aspects of joint mechanics are related. The investigators used a computational model that included gait mechanics and anatomic information from CT scans to look at whether the anterior-posterior (AP) translation (front-to-back movement) of the femur with respect to the tibia while walking was correlated with bone-implant micromotion after surgery. Based on their models, they determined that the AP translation significantly related to the peak micromotion throughout gait, especially in the lateral portion of the knee; greater AP translation resulted in larger micromotions. This study highlights the connection between joint-level mechanics and fixation-level mechanics in TKA surgery and is the first time researchers at HSS have been able to look at both in tandem.

Authors: Jonathan Glenday, PhD, Peter K. Sculco, MD, Jonathan M. Vigdorchik, MD, Joseph D. Lipman, MS, Cynthia Kahlenberg, MD, David J. Mayman, MD, Timothy M. Wright, PhD,  Fernando J. Quevedo-González, PhD.

Three-Dimensional Functional Impingement in Total Hip Arthroplasty: A Biomechanical Analysis

Impingement after THA can lead to pain and, in the worst case, a dislocation of the prosthesis. Offset of components, which is related to the width of the hip, directly affects the impingement of the hip after surgery. Surgeons have multiple ways to alter offset during THA surgery; however, these alterations have only been studied in two dimensions. A team led by HSS hip and knee surgeon Jonathan M. Vigdorchik, MD, and former clinical fellow Eytan Debbi, MD, PhD, used 3-D models created from pre- and postoperative CT scans of 16 patients who underwent the procedure to retrospectively analyze the relationship between offset and impingement. They compared cup/liner (acetabular) offset to head/stem (femoral) offsets and looked at the effects that these configurations had on the patient’s range of motion and incidence of impingement after surgery. The investigators found that in all cases, increasing the offset reduced the amount of impingement, and increased the full range of motion of the hip. Acetabular offsets had greater impact than femoral offsets in the range of motion because they affect the offset of the center-of-rotation.

Authors: Eytan Debbi, MD, PhD (Cedars-Sinai), Fernando J. Quevedo-González, PhD, Seth A. Jerabek, MD, Timothy M. Wright, PhD, Jonathan M. Vigdorchik, MD.

An innovation in the growing field of remote patient monitoring, it is the first implantable device approved to collect data on an individual’s progress after a total knee replacement − vital information securely relayed to a cloud-based platform for the orthopedic surgeon to review.

Known as the Persona IQ, the smart knee was granted authorization from the U.S. Food and Drug Administration (FDA) in August. Although the technology doesn’t preclude office visits altogether, it enables the doctor to actively monitor a patient’s recovery with real-world, objective data to supplement their care.

Remote monitoring can be especially useful during the early post-operative period, Dr. Sculco says. “In the first several weeks following knee replacement, hard work is required from the patient, and there can be deviations in recovery that can set people on the wrong path. The earlier you identify a patient who may not be progressing as well as you would like, the sooner you can intervene,” he explains. “This could mean a change in an individual’s physical therapy plan, enhanced patient education, anti-inflammatory medication or the use of an ice machine. When I go into the exam room to see a patient at the six-week follow-up visit, I should have a very granular understanding of how his or her recovery is going.”

The smart knee contains a sensor that is integrated into the joint replacement prosthesis. Once implanted, it records and wirelessly transmits gait data and other information to a personal base station, about the size of a modem, that plugs into an outlet at the patient’s home. The data is then securely sent to a cloud-based platform where the orthopedic surgeon can review it and check on the patient’s progress and recovery.

“The smart knee uses the same material and technology found in implanted cardiac devices such as pacemakers,” explains Dr. Cushner, who is also a founder and chief medical officer of Canary Medical, the company that designed the sensor technology. “It collects data every day during the first year following surgery, providing objective, accurate information on how the knee is functioning. Patient monitoring can continue for much longer, though, as the battery that powers the device was made to last at least 10 years.”

Dr. Sculco notes that as time goes by and more patients receive the smart implant, it has the potential to amass a vast amount of information on gait metrics following knee replacement. Down the road, orthopedic researchers could potentially use data analytics and machine learning to translate that information into evidence-based recommendations to ultimately improve outcomes and enhance patient care.

Stiffness after knee replacement surgery, or total knee arthroplasty (TKA), is a rare but frustrating complication, affecting between 1% and 7% of patients who receive the artificial joints. “Why some people and not others experience limited range of motion after TKA is unknown,” said Ioannis Gkiatas, MD, PhD, an orthopedic surgeon at the University of Ioannina, in Greece, and the first author of the new study who also recently completed a research Complex Joint Reconstruction fellowship at HSS.

“The goal of the study was to see if we can help physicians predict how patients will do following the revision surgery, using information gathered before and after the procedure, to shape their postoperative treatment plans,” said Dr. Gkiatas. The work was conducted under the supervision of Peter K. Sculco, MD, hip and knee surgeon at HSS, who is leading a large, ongoing study of patient outcomes after revision TKA for reduced range of motion after index TKA.

For the study, Drs. Gkiatas, Sculco and their colleagues followed 19 men and women who underwent revision TKA at HSS to try to improve stiffness in patients with prior TKA. Patients underwent range of motion testing before the procedure and at six weeks, six months and one year after the operation.

A healthy knee has a wide range of motion — from full extension (0 degrees) through the sitting position (90 degrees) to kneeling (approximately 140 degrees). All patients gained some mobility after the revision surgery, with the average improvement being approximately 28 degrees of motion. Most of the benefit appeared to occur in the first six weeks after the operation, then gradually tapered off over time.

The researchers found that patients with the least restricted mobility experienced the greatest gains from the revision surgery. Patients who could bend their affected knee more than 82 degrees before TKA revision had an 80 percent chance of maintaining that level of mobility, or gaining flexibility in the joint, after the operation and throughout the follow-up period.

However, two-thirds of patients whose range of motion was less than 64 degrees before surgery experienced regression in that mobility across all time points of the study and never attained the 82-degree threshold.

“Although 82 degrees doesn’t seem much more than 64 degrees, for the patient it’s a significant difference. With 82 degrees you can perform the basic activities of everyday life,” Dr. Gkiatas said. “With these new data, if at six weeks a patient reaches 82 degrees of motion in their knee, we can say they have an 80 percent chance of at least maintaining this range of motion one year after surgery.” The results of this study provide surgeons with the information needed to educate patients with stiff TKA on expected range of motion outcomes after revision surgery. Less than 60 degrees being a poor prognostic finding. In addition, when patients return to the office for their six-week appointment after revision TKA, and have less than 82 degrees of motion, additional pharmacologic or manual knee manipulation treatments should be implemented as this patient is at a high risk for range of motion regression and inferior clinical outcome at one-year post-revision.

With construction beginning this year, the Anna-Maria and Stephen Kellen Medical Tower will be located adjacent to the main hospital on 70th street and extend over FDR Drive. At 12 stories and 100,000 square feet, this new facility will provide a specialized environment for joint replacement and spine care—including some of the most complex and debilitating orthopedic conditions. The medical tower will include three private inpatient floors, multidisciplinary medical teams, and on-site imaging to support high-quality musculoskeletal care.

The transformational gift builds on the Foundation’s long history of support for HSS—totaling almost $60 million over the last decade. “We were inspired by all lives that will be changed in this new building,” said Marina Kellen French, Vice President of the Foundation and an HSS trustee. “I care deeply about HSS and the decision to make this gift was very personal. I have a close friendship with Dr. Thomas Sculco [Surgeon-in-Chief Emeritus] that goes back over 30 years, and support of this project is also a reflection of our belief in talented doctors like him.”

Mrs. Kellen French has served on the HSS Board of Trustees and Board of Advisors for more than 10 years and together with the Foundation, has made an indelible mark on the organization—helping to shape the careers of young investigators, blaze new paths for scientific inquiry, and transform how HSS cares for those affected by musculoskeletal conditions. “The Anna-Maria and Stephen Kellen Foundation has repeatedly demonstrated their commitment and support to HSS and its patients,” said Tom Lister and Bob Steel, co-chairs of the Board of Trustees. “This exceptional gift signals the strength of not only HSS but also New York City and will serve as a permanent symbol of an investment in healthcare when it is needed most.”

An increasing number of patients will be counting on HSS for care in the coming years, and construction of this building is essential to meet this need. “The gift will allow us to expand access to all who can benefit from our expertise in delivering the highest-quality of musculoskeletal care,” said Louis A. Shapiro, president and CEO at HSS. “We thank Mrs. Kellen French and the Foundation for their generosity and their commitment to this extremely important project that will continue to help people get back to what they need and love to do."

HSS is the world’s largest academic medical center specialized in musculoskeletal health, spanning orthopedics, rheumatology and related disciplines. The HSS Research Institute maintains 20 laboratories dedicated to solving debilitating orthopedic and rheumatic conditions such as arthritis, bone and soft tissue injuries, autoimmune diseases, and musculoskeletal pain and deformities. There, more than 300 dedicated personnel focus on tissue repair, improving surgical outcomes, autoimmunity and inflammation, genomics, new treatments, and precision medicine.

“HSS has a long history of contributing to the collective base of clinical and basic science knowledge and finding healthcare solutions for complex conditions,” said Louis A. Shapiro, President and CEO, HSS. “We’re proud that through the joint efforts of our institution and philanthropic support, we will have the ability to make a strong impact on this growing and vital area of research.”

“As experts in inflammatory disorders and in the development of interventions for overactive immune responses, the clinicians and researchers at HSS are well-positioned to investigate many of the adverse effects of COVID-19,” says Lionel B. Ivashkiv, MD, Chief Scientific Officer at the HSS Research Institute. “This includes studying the causes of these adverse effects as well as how to prevent and treat them.”What follows are descriptions of the first group of funded projects in basic/translational research:

Activation of pDCs by SARS-CoV-2 and Its Impact on Macrophage Response

Principal Investigator: Franck Barrat, PhD

Co-Investigator: Marie-Dominique Ah Kioon, PhD

This project will study cell types that are responsible for cytokine storm syndrome — the hyperactive immune response seen in people with COVID-19 — by looking at how certain immune cells are activated by SARS-CoV-2. Research in mice infected with SARS-CoV, a coronavirus similar to the one that causes COVID-19, has suggested that plasmacytoid dendritic cell precursors (pDCs) are key to the immune response to infection. These pDCs activate macrophages, which in turn secrete cytokines. In the SARS-CoV research, depletion of pDCs appeared to protect the mice from lethal lung injury. Using blood samples from donors, the investigators will study the pathway by which pDCs activate macrophages and look at ways to therapeutically block that process.

Inhibiting RNA Polymerase II Transcription Complexes in Macrophages to Target COVID-19–Associated Cytokine Storm

Principal Investigator: Inez Rogatsky, PhD

Co-Investigators: Steven Josefowicz, PhD, and Robert P. Fisher, MD, PhD

This pilot project will dissect the role of macrophages in SARS-CoV-2-induced acute respiratory distress syndrome (ARDS), the main driver of COVID-19-associated mortality. We will test small-molecule inhibitors of RNA Polymerase II (Pol II) transcription complexes for their ability to modulate type I interferon and inflammatory pathways in monocytes/macrophages. This research will be done using cultured macrophages as well as donor blood and blood from COVID-19 patients.

Mechanisms of Cytokine Storm in Patients with COVID-19

Principal Investigator: Mary K. Crow, MD

Co-Investigators: Mikhail Olferiev, MD, and Lionel B. Ivashkiv, MD

The objectives of this study are to describe the process of the cytokine storm in people with COVID-19 and to identify biologic predictors of a favorable outcome in patients with severe cases of the disease. The project aims to characterize immune cell populations seen in COVID-19 patients who experience cytokine storm and compare them to those patients who do not, to compare the immune response before and after patients are given the anti-inflammatory drug anakinra, and to identify measures that suggest patients are more likely to decline and eventually require mechanical ventilation. The research will employ blood samples from HSS patients who are being treated for COVID-19 at New York–Presbyterian Hospital and who meet certain other qualifications.

What follows are descriptions of the first group of funded projects in the areas of clinical and health outcomes research:

Response to and Recovery from TKA in Patients with Antibodies to SARS-CoV-2

Principal Investigator: Miguel Otero, PhD

Co-Investigators: Meghan Kirksey, MD, PhD, and Peter K. Sculco, MD

It is unknown if people who have been exposed to COVID-19 may be at higher risk of experiencing an abnormal immune response following surgery, resulting in poor outcomes. This study will evaluate the response to and recovery from total knee arthroplasty (TKA) in people who have antibodies to COVID-19 — a marker of exposure. This study will include both patients who have COVID-19 antibodies and those who don’t, to act as controls. Patients will be followed for six weeks after surgery and evaluated for the presence of certain immune markers in the blood, as well as symptoms of inflammation including pain and stiffness in the joint.

SARS-CoV-2 Exposure and the Role of Vitamin D Among Hospital Employees

Principal Investigator: Emily M. Stein, MD, MS

Co-Investigators: Theresa T. Lu, MD, PhD; Andy O. Miller, MD; Jeri Nieves, PhD; and Alana Serota, MD

It is unknown if people with vitamin D deficiency may be more likely to become infected with COVID-19. This study will investigate vitamin D status and associated immune markers as risk factors for COVID-19 infection in a cohort of healthcare workers. Healthcare workers are at higher risk of contracting COVID-19 than the general population, making them a good group to study. Vitamin D is critical for immune function and is known to be protective against respiratory-tract infection and tuberculosis. This prospective, observational study will follow healthcare workers at HSS and at other healthcare facilities for one year, to determine whether levels of vitamin D and certain immune cells in the blood make someone more susceptible to COVID-19 infection.

Association of Immunomodulatory Medication Use and Social Determinants of Health with COVID-19 Infection in Systemic Rheumatic Disease Patients in New York City

Principal Investigator: Medha Barbhaiya, MD, MPH

Co-Investigators from HSS: Lisa Mandl, MD, MPH; Catherine MacLean, MD, PhD; Vinicius Antao, MD, PhD; Jane Salmon, MD; and Mayu Sasaki, MPH

Other Co-Investigators: Candace Feldman, MD, MPH (of Brigham and Women’s Hospital); Debra D’Angelo, MS (of Weill Cornell Medicine)

Using data from the INSIGHT Clinical Research Network, a central repository containing longitudinal electronic health data for residents of New York City, investigators will assemble a cohort of patients being treated with immunomodulatory medications for rheumatic disease. This patient population will then be used to study the effect of these medications on COVID-19 incidence and outcomes. Retrospective data will be used to evaluate the incidence and severity of COVID-19 in these patients. Patients will also be studied prospectively to determine whether there’s a relationship between COVID-19 infection and future rheumatic disease as well as to study connections between infection and future psycho-social issues.

Assessment of Surgical Outcomes in the COVID-19 Pandemic Era

Principal Investigator: Andy O. Miller, MD

Co-Investigators: Scott A. Rodeo, MD, and Mark Fontana, PhD

Investigators will implement a patient registry to evaluate how COVID-19 affects outcomes and complication rates after orthopedic surgery. This registry, along with COVID-19 screening procedures, will provide the tools to address specific research questions. Among these questions are determining the incidence of current and prior infection among the HSS surgical population, the clinical features associated with current and prior infections in this patient population, and whether COVID-19 status affects short-term complication rates.

What follows is a description of an integrated multidisciplinary study being undertaken jointly by the Adult Reconstruction and Joint Replacement (ARJR) Perioperative Research Group, Anesthesiology and Rheumatology:

Prediction and Prevention of Postoperative Blood Clots in COVID-19 Patients

Principal Investigators: Friedrich Boettner, MD; Kethy M. Jules-Elysee, MD; Lisa A. Mandl, MD, MPH

Co-Investigators: ARJR surgeons: Alejandro Gonzalez Della Valle, MD; Jason Blevins, MD; David J. Mayman, MD; Peter K. Sculco, MD; Geoffrey H. Westrich, MD and Thomas P. Sculco, MD

Medicine/Rheumatology: Medha Barbhaiya, MD, MPH; Doruk Erkan, MD, MPH; Deanna Jannat-Khah, DrPH

Pathology: Thomas W. Bauer, MD, PhD

Anesthesiology: Stavros G. Memtsoudis, MD, PhD, MBA; Alexandra Sideris, PhD

ARJR: Amethia Joseph, MHA; Ethan Krell, MS

Weill Cornell Medicine: Raymond David Pastore, MD

Recent literature suggests that one of the major complications seen in people with COVID-19 is thrombosis (the formation of blood clots) due to endothelial dysfunction, persistent inflammation and potentially antiphospholipid antibodies. As elective surgeries resume, those with prior exposure to SARS-CoV-2 will inevitably present for treatment, and some may have perioperative management considerations related to their risk of deep-vein thrombosis. This project will use, a noninvasive device that can determine clotting risks, to investigate whether people who have had COVID-19 have a more dysfunctional endothelium preoperatively and at 24 hours after surgery. The investigators will measure antiphospholipid antibodies and inflammatory markers, and evaluate the prevalence of asymptomatic post-operative deep-vein thrombosis in people who undergo TKR and have SARS-CoV-2 antibodies.

COVID-19 Translational Research Core at HSS

Principal Investigator: Theresa Lu, MD, PhD

Co-Investigators: Jessica Andrés-Bergós, PhD; Miguel Otero, PhD and Emily M. Stein, MD, MS

The COVID-19 Translational Research Core (TRC) was designed to fill critical gaps in the resources needed to promote the broad range of COVID-19–related clinical and translational research at HSS. The TRC will provide consultation on the design and implementation of COVID-19 research in the areas of orthopedics, rheumatology and metabolic bone disease; support for a COVID-19 biobank; and technical expertise and facilities required for clinical and translational researchers working on COVID-19–related projects. The TRC staff will help to acquire, house, and track biospecimens from investigator-initiated COVID-19–related research studies.

Researchers retrospectively examined all patients undergoing a posterior primary uncemented total hip replacement between January 2014 to June 2016 at HSS. 

Eliminating guidelines did not increase the risk of hip dislocation for the low risk population. "The majority of patients we see are low risk; 90 percent of patients probably qualify for minimized precautions," said Peter K. Sculco, MD, the study's lead author and an orthopedic surgeon at HSS.

Read the full article at Becker’s Spine Review.

"The precautions can be limiting and cause fear in patients," says Peter K. Sculco, MD, hip and knee surgeon and study author. "Sleeping on your back is very uncomfortable for many people. You often hear from physical therapists that patients are relieved when they can finally cross their legs and sleep on their side."

Read the full article at UPI.com.

"The precautions can be limiting and cause fear in patients," said Peter K. Sculco, MD, the study’s lead author. "Sleeping on your back is very uncomfortable for many people. You often hear from physical therapists that patients are relieved when they can finally cross their legs and sleep on their side."

When patients are on stringent precautions, they are not as active, and this can hamper recovery. "If you minimize the hip precautions in an appropriate way, patients focus more on their mobility and recovery and less on the fear of how they turn their leg ten degrees," said Dr. Sculco.

Read the full article at ScienceDaily.com.

"The majority of patients we see are low risk; 90% of patients probably qualify for minimized precautions," said Peter K. Sculco, MD, the study’s lead author and an orthopedic surgeon specializing in hip and knee replacement at HSS. 

In the last ten years, surgeons have started favoring the anterior approach (through the back of the hip) for total hip replacement over the posterior approach, because it doesn’t involve standard hip precautions. Little data, however, backs the standard hip precautions recommended for the posterior approach. For a posterior approach, standard precautions are not flexing your hip past 90 degrees, not internally rotating your hip more than 10 degrees, using an elevated seat cushion at all times and a grabber for anything that is on the ground, and sleeping on your back for six weeks. 

"The precautions can be limiting and cause fear in patients," said Dr. Sculco.  "Sleeping on your back is very uncomfortable for many people. You often hear from physical therapists that patients are relieved when they can finally cross their legs and sleep on their side."

The literature showing that hip precautions make a difference in hip dislocation is poor. "The current precautions are based on hip replacements done 25 years ago, and we have changed a lot in terms of improving how we do hip replacements that has given us more confidence in the stability of our hips," said Dr. Sculco. "Our understanding of the dynamic movement of the pelvis and how we put the parts in is much different. The quality of our soft tissue repair and closure at the end of surgery is much more robust."

When patients are on stringent precautions, they are not as active, which can hamper recovery. "If you minimize the hip precautions in an appropriate way, patients focus more on their mobility and recovery and less on the fear of how they turn their leg ten degrees," said Dr. Sculco. 

In the new study, researchers retrospectively reviewed all patients undergoing a posterior primary uncemented total hip replacement (total hip arthroplasty) from January 2014 to June 2016 at HSS. Surgeons had the choice to put patients on standard precautions or a pose avoidance protocol, to avoid a single pose, a flexed external rotation position that occurs when a person puts on their shoe or shaves their leg. A total of 1,311 patients met the inclusion criteria for the pose avoidance cohort, and the minimum followup was six weeks. Researchers then matched patients 1:1 in this group to a historical cohort of patients based on age, gender, and body mass index that were treated with standard posterior hip precautions. 

Within the first six postoperative weeks, six dislocations occurred in the pose avoidance group (0.46%) compared with seven in the matched group (0.53%), a difference that was not statistically or clinically significant. "Our results suggest that the standard postoperative precautions in patients undergoing total hip arthroplasty through the posterior approach without known risk factors for instability are unnecessary," said Dr. Sculco. "We may find that precautions don’t make sense for any of our patients, but we need to look at in a stepwise fashion." Risk factors include neuromuscular issues, such as stroke, Parkinson’s disease and lumbar spine fusions.

The study was limited in that it is not a randomized controlled trial, usually the gold standard for dictating a change in practice. "The bottom line of the study is in recent years, we have learned more about interventions that matter after joint replacement and those that don’t really have efficacy. In most patients, we got rid of powerful anticoagulants, for example, and we are moving toward a shorter stay and even outpatient arthroplasty for total hip replacement," said Dr. Sculco. "Minimizing precautions and simplifying the postoperative recovery is part of the larger simplification of surgery where we are using more selected resources and interventions for people, instead of blanketing everyone with the same kind of protocols."

Dr. Sculco noted that there is an increasing demand for hip replacement in the United States. "In 2010, there were 310,000 hip replacements in the United States and that number is increasing. It is probably 350,000 if not more now," said Dr. Sculco.

In 2017, more than 47,000 Americans died after overdosing on opioids, such as heroin or fentanyl, a potent synthetic drug, government data show. Some 1.7 million more had a substance abuse disorder involving a prescription opioid. 

Patients who undergo joint replacement surgeries of all kinds conventionally have received an opioid prescription for their recovery—presenting critical opportunity for reducing the reliance on these medications and preventing abuse of the drugs. 

HSS is taking a multi-pronged approach to the problem, explained Michael P. Ast, MD, an orthopedic surgeon at the institution. HSS recently launched a hospital-wide initiative to reduce opioid use among its patients and to better understand when the powerful drugs are appropriate to prescribe, and in what quantities. The initiative has involved surgeons, anesthesiologists, nurses and other members of the care team.

A primary focus of the pain-management pathway is the emphasis on multimodal analgesia. The practice involves the combination of local anesthetics, nonsteroidal anti-inflammatory drugs, IV acetaminophen and, possibly but not necessarily, opioids. Multimodal analgesia for knee and hip replacement surgeries has been associated with a decrease in the use of opioids, according to the American Society of Anesthesiologists (https://www.asahq.org/about-asa/newsroom/news-releases/2018/03/multimodal-approach-to-pain-management-reduces-opioid-use).

Another aspect of the initiative involves research, and HSS currently has more than a dozen ongoing studies to assess alternatives to opioid analgesia. "We’re doing things like intraoperative and post-op acupuncture therapy and we’re looking at alternative treatments in the form of nerve blocks," said Peter K. Sculco, MD, orthopedic surgeon at HSS and also senior author on the study said. "We’re also looking at understanding prescribing patterns and how that affects how patients use their medication—if they are given a smaller prescription will they use less over time?"

The effort also has a strong patient-centered component. The new pain-management pathway includes educational programs for patients undergoing joint surgeries, including new additions to the preoperative education to manage pain expectations, early intervention by the pain management team for patients on preoperative or chronic opioids, and a multi-disciplinary inpatient team to treat and educate patients on alternatives to opioids for pain management. Although still in its early phase, data so far show that the pathway has led to a significant decrease in the use of opioids with no sacrifice in pain control. 

Dr. Sculco and his colleagues presented their findings at the 2019 annual meeting of the American Academy of Orthopaedic Surgeons in Las Vegas (exhibit SE35).

Other authors include: Ameer Elbuluk, MD; Michael Alexiades, MD; and Michael Cross, MD; all from HSS.

For more information on opioid prescription and pain management at HSS, please view the February 2019 issue of HSS Journal.

"In terms of pain and function, there was a recent meta-analysis looking at a number of studies that showed that neutral mechanically aligned total knees have a large and sustained positive effect on improving pain and function in patients and are very effective in treating knee osteoarthritis," said Dr. Sculco during the debate at the Annual Current Concepts in Joint Replacement (CCJR) Spring meeting in Las Vegas, Nevada.

"Neutral mechanical alignment is guaranteed with good data… Kinematic alignment requires continued close surveillance; additional testing, new implant development and limited adoption until more data is available," he added.

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

"[Knee stiffness is] a vexing problem that, with manipulation, we can treat with success 85% of the time. For those resistant types, it can lead to surgical treatments which have their own varying success rates, but, in essence, it is a problem we still need to work on, as a field, to improve both its prevention and also how we better treat it," said Dr. Sculco.

According to Dr. Sculco, knee stiffness can be caused by a variety of factors.

"Patient-related factors... are demographic and related to comorbidities. You have knee-related factors, most significantly previous surgical procedures or having preoperative stiffness. You have mental health-related factors, and you have nerve-related factors. So, there is a long list of things that can lead to a postoperative stiff knee," he said.

Additionally, Dr. Sculco said knee stiffness could be treated with manipulation under anesthesia (MUA).

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