“We have been interested in studying UCTD because it’s commonly encountered in clinical practice but not well characterized,” said lead study author Caroline Siegel, MD, a rheumatology fellow at HSS. “UCTD is inherently challenging to define, but it’s very important to understand what features differentiate patients with UCTD from those with defined connective tissue diseases (CTD) such as lupus so that we can better manage patients with this condition and ultimately predict who may go on to develop more severe clinical manifestations.”

The study included 89 patients aged 18 years and older treated at HSS between 2018 and 2022 who had rheumatologist-diagnosed UCTD with positive antinuclear antibody and at least one sign or symptom of CTD. The researchers reviewed medical records to identify those who fulfilled established classification criteria for systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis, primary Sjögren’s, idiopathic inflammatory myopathy, or antiphospholipid syndrome (APS). The researchers compared sociodemographic, clinical, serologic, and treatment variables between 59 patients with UCTD and 30 patients who fulfilled criteria for CTD.

Patients in both groups had similar non-criteria manifestations, most commonly joint pain and fatigue. However, patients with UCTD were less likely to have arthritis, criteria-based hematologic manifestations, anti-double stranded DNA or anti-Smith antibodies, and hypocomplementemia. The frequency of RA, Sjögren’s, and APS-related serologies did not differ between groups. Compared to those with CTD, UCTD patients were less likely to have ever received systemic corticosteroids.

“Our main findings were that patients who met a strict definition of UCTD versus those who met classification criteria for other CTDs were less likely to have clinical and laboratory features such as arthritis and hematologic abnormalities, as well as certain autoantibodies that are commonly seen in lupus,” said Dr. Siegel. “They were also less likely to have received treatment with steroids,” she added.

The results reveal that even among patients diagnosed by their treating physician with UCTD, some may meet classification criteria for other rheumatic diseases. Within this group, patients with strictly defined UCTD may differ in meaningful ways.

“We are starting to recognize features of strictly defined UCTD that will allow us to better identify and manage this condition,” said senior study author Medha Barbhaiya MD, MPH, rheumatologist at HSS. “Patients struggle with the uncertainty of a UCTD diagnosis and our study aimed to demonstrate that UCTD may be a distinct entity from other rheumatic conditions. These findings lend support to the claim that patients who have UCTD require separate study, and their disease manifestations warrant further understanding.”

Findings identified long-haul COVID was particularly high for smokers, patients with comorbidities such as asthma or lung disease, cancer, chronic kidney disease, diabetes, congestive heart failure or myocardial infarction, and those taking corticosteroids.

“Knowing the impact of this problem is critical,” said Medha Barbhaiya, MD, MPH, a rheumatologist at HSS who led the study. “For rheumatology patients, long-haul COVID may be particularly challenging as these patients already have significant chronic health issues and warrants further investigation.”

Dr. Barbhaiya and her colleagues presented their study, “Risk Factors for ‘Long Haul’ COVID-19 in Rheumatology Outpatients in New York City,” at the American College of Rheumatology (ACR) annual meeting.

For the study, Dr. Barbhaiya’s group emailed surveys to 7,505 men and women aged 18 years and older who had been treated at HSS for rheumatologic complaints between 2018 and 2020. Participants were asked if they had received a positive test for COVID-19 or if they had been told by a healthcare provider that they had contracted the infection.

The researchers defined long-haul COVID-19 infections as those with symptoms lasting one month or longer, whereas limited-duration cases were considered those with symptoms lasting less than one month.

Among the 2,572 individuals who completed the survey, nearly 56% of patients who reported having contracted COVID-19 said their symptoms lasted at least one month. Only two patients in the study had a previous diagnosis of fibromyalgia — a condition marked by fatigue, muscle aches and other symptoms that have been associated with long-haul COVID — suggesting that overlap between the two disorders is minimal.

“Our findings do not suggest that symptoms of fibromyalgia are being misinterpreted as long haul COVID in patients with rheumatic diseases, which is something that has been raised as a possibility,” said Lisa A. Mandl, MD, MPH, a rheumatologist at HSS and senior author of the new study.

HSS researchers plan to use the data as part of a longitudinal analysis of rheumatology patients with long-haul COVID to determine if the lingering symptoms of the infection interfere with their rheumatologic conditions. Ongoing surveillance of these patients will provide important insight on the long-term impact of COVID-19 in patients with rheumatic disease.

“The results may provide some reassurance to physicians who are taking care of women with rheumatic diseases who become pregnant or who are contemplating pregnancy during the pandemic, because there does not seem to be an increased risk of COVID-19, but the findings need to be interpreted with caution given that in other national datasets including the Centers for Disease Control and Prevention data, pregnant patients who get COVID-19 have been shown to have potentially more severe outcomes,” said lead study author Medha Barbhaiya, MD, MPH, rheumatologist at HSS and assistant professor of medicine and healthcare policy & research, Weill Cornell Medicine.

For their study, Dr. Barbhaiya and her colleagues emailed an online COVID-19 survey to 26,045 patients in the Division of Rheumatology at HSS. 7,094 responded with 1,547 in the targeted population of women age 18 to 50. 4% reported pregnancy.

The prevalence of self-reported COVID-19 was similar in pregnant and non-pregnant women (8% vs. 9% respectively; P=0.76). Among women with COVID-19, pregnant women had a shorter duration of symptoms (P<0.01) and were more likely to experience loss of smell or taste (P=0.02) than non-pregnant women. A systemic rheumatic disease was present in approximately three-fourths of women, with no differences when stratified by pregnancy or COVID-19 status. While 67% of pregnant women reported changes to prenatal care during the pandemic, 23% of postpartum women stated the pandemic affected delivery.

“These findings are novel and should be investigated in other cohorts. Future studies will hopefully assess the long-term outcomes of rheumatology patients and their offspring who were exposed to COVID-19 during pregnancy, which our cross-sectional study could not address,” said Dr. Barbhaiya.

“Why pregnant patients are more likely to present with these symptoms warrants further study. This unique finding may help us better understand the immunology of both conditions,” said senior study author Lisa A. Mandl, MD, MPH, rheumatologist at HSS and assistant professor of medicine and healthcare policy & research, Weill Cornell Medicine. “These data also suggest that testing for COVID-19 in otherwise well pregnant women who lose their sense of taste or smell may help in the timely identification of COVID-19 in these vulnerable patients.”

In their paper, published online ahead of print on November 30, 2020, in Arthritis Care & Research, the investigators reported on the first two of four phases of criteria development. Phase I and II involved generating 261 candidate criteria for defining APS and reducing the list to 27 finalist criteria, grouped into six specific categories: laboratory tests, macrovascular, microvascular, obstetric, cardiac and hematologic. The ultimate goal is to develop a threshold-based scoring system that will allow researchers worldwide to determine which patients most likely have APS and should be included in research studies.

APS is an autoimmune disorder in which the immune system produces antibodies against specific normal proteins in the blood, causing clots in blood vessels, low platelet counts, heart valve abnormalities and pregnancy complications. It is the leading cause of stroke in young people, causing one in three strokes in people under the age of 50, one in five recurrent miscarriages and up to 20 percent of all deep vein thromboses. The disease is often found in patients with other autoimmune conditions, especially lupus.

The current APS Sapporo Classification System was published in 1999, validated in 2000, and revised in 2006. “The previous classification system was based on the available evidence at the time,” says lead author Medha Barbhaiya, MD, MPH, rheumatologist at the Barbara Volcker Center for Women and Rheumatic Diseases at HSS and assistant professor of medicine and population health sciences at Weill Cornell Medicine. “In the last decade, researchers have identified additional features of APS that deserve inclusion. We also now have more rigorous methods for developing and validating disease classification criteria.”

The international initiative is jointly funded by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR), in recognition of the need for improving the method of classifying patients for APS research to be used worldwide. Doruk Erkan, MD, MPH, rheumatologist at the Barbara Volcker Center for Women and Rheumatic Diseases at HSS and associate professor of medicine at Weill Cornell Medicine, is the senior author and co-principal investigator together with Stephane Zuily, MD, MPH, PhD, a vascular medicine specialist and professor of medicine at the Université de Lorraine, Nancy, France.

Emphasizing the difference between classification versus diagnosis criteria for APS, Dr. Erkan says, “Classification criteria are intended to be used in a research setting whereas diagnostic criteria are used in a clinical setting for the purpose of managing diseases; the two sets of criteria may have overlapping elements, but they have separate goals. The goal of classification criteria is to ensure that patients with common characteristics, thought to be specific for a certain disease, are included in appropriate research studies. In contrast, the goal of diagnostic criteria is to identify, as accurately as possible, whether patients have that particular disease.”

The next phase of the new APS classification criteria methodology involves defining, refining, and weighting the candidate criteria and assigning a threshold score for identifying APS using real-world cases and a computer-based decision tool. Following the final validation phase of the project, researchers plan to report their results in 2021. Dr. Barbhaiya is also supported by a separate but related grant, the 2018 Rheumatology Research Foundation Investigator Award, to investigate risk factors for APS using the data collected during new classification criteria development.

“We are excited to be developing validated classification criteria for APS as previously done for other rheumatologic diseases, such as lupus and rheumatoid arthritis,” says Dr. Erkan, who is also co-chair of the AntiPhospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION). “A threshold score for identifying patients with the disease will go a long way to advancing APS research, with the ultimate goal of high-quality research to improve APS prevention and treatment options for patients.”

The research focuses on the diagnosis of renal disorders, the risk of venous thromboembolism after total knee replacement (TKR), and the care of pediatric and young adult patients with rheumatologic diseases. There are also studies related to the care of rheumatology patients during the COVID-19 pandemic.

“While there have been significant advances in science over the years, there are areas of unmet needs warranting continued investigation,” said S. Louis Bridges, Jr., MD, PhD, Physician-in-Chief, Chair of the Department of Medicine and Chief of the Division of Rheumatology at HSS. “HSS has a relentless focus on improving patient care through innovation and discovery. By spearheading multi-center studies, clinical trials, and laboratory-based research, we continue to improve the quality of life for patients affected by rheumatic and musculoskeletal conditions.”

What follows are some highlights from the meeting:

Geographical Variations in COVID-19 Perceptions and Patient Management: A National Survey of Rheumatologists

A study led by HSS rheumatologist Bella Mehta, MBBS, MS, looked at the perceptions and behaviors of rheumatologists in the United States regarding the risk of COVID-19 for patients with autoimmune disorders and how those patients were managed with immunosuppressive and anti-inflammatory medications. The 271 respondents were asked whether patients with rheumatic diseases were at higher risk of COVID-19 and whether the pandemic had led them to reduce the use, dosage, or frequency of biologics or steroids. Overall, the survey found geographical variations regarding perceptions of patients’ risk of COVID-19, with responses that were significantly different in the Northeast region of the United States compared with other regions.

Can a Clinical Disease Activity Index Based on Patient-Reported Joint Counts (PT-CDAI) Be Used to Inform Target-Based Care in Telemedicine? An Analysis of 2 Early RA Cohort Studies 

A team that included HSS rheumatologist Vivian P. Bykerk, BSc, MD, FRCPC, looked at data from two cohort studies on patients with early rheumatoid arthritis (RA) that compared patient and physician assessment of tender and swollen joints. This research is important because COVID-19 has forced rheumatologists to shift from in-person clinical visits to telemedicine, which limits their ability to carry out complete joint exams. The study found that patient and physician assessments had good agreement when it came to identifying active versus controlled disease activity. In addition, the researchers reported that predictors of higher discrepancies between patient and physician assessments may help identify patient subsets that could benefit the most from more physician-guided training at joint self-assessments as well as more probing questioning during telehealth visits to confirm active synovitis.

Characterization of Antiphospholipid Antibody-Associated Nephropathy: An International Survey of Renal Pathology Society Members

A survey led by HSS rheumatologist Medha Barbhaiya, MD, MPH, sought to determine whether pathologists worldwide use uniform criteria to distinguish antiphospholipid antibody-associated nephropathy (aPL-N) from other forms of thrombotic microangiopathy. The study was done in parallel with an international effort to develop new classification criteria for antiphospholipid syndrome. The web-based survey included 780 members of an international Renal Pathology Society; 111 renal pathologists responded, representing 33 countries. The participants were asked to determine whether two acute and eight chronic aPL-N features were consistent with acute or chronic aPL-N without and were not provided with serology information. Results from the survey indicated that more than 90% of pathologists worldwide agreed that the renal pathologic features most specific for aPL nephropathy are noninflammatory glomerular or small arterial microthrombi and organized microvascular thrombi with recanalization. In the absence of serologic data, more than 75% of pathologists indicated lack of specificity of chronic glomerular or small arterial changes. These findings indicate the importance of serologic test results in biopsy interpretation and suggest higher specificity for certain acute or chronic features.

The Risk of Venous Thromboembolism After Septic Total Knee Replacement (TKR) Revision Is Double the Risk After Aseptic TKR Revision: An Analysis of Administrative Discharge Data

A team led by HSS rheumatologist  Anne R. Bass, MD, assessed the 90-day risk of postoperative venous thromboembolism (VTE) in people who underwent revision TKR surgery. Although it was already known that infection can increase the risk of thrombosis by triggering coagulation pathways, the impact of infection in this context was not well understood. The study, which included 25,441 of these surgeries performed between 1998 and 2014, used data from the New York Statewide Planning and Research Cooperative System. Overall, 69% of these revisions were for mechanical causes (aseptic), 28% were for infection (septic), and 3% were related to a periprosthetic fracture. The researchers found that the risk of VTE after septic revision surgery was double the risk after aseptic revision surgery, and was 2.6-fold higher after revision surgeries for fracture. These findings point to the importance of taking infection and fracture status into account when planning VTE prophylaxis for patients having revision surgery.

Using a Patient-Engaged Approach to Identify Cross-Cutting Disease Factors Impacting Mental Health in Youth with Rheumatologic Disease

A team including HSS chief of pediatric rheumatology Karen Brandt Onel, MD, examined the mental health experiences of those with juvenile arthritis, juvenile dermatomyositis, or systemic lupus erythematous. It included patients aged 14 to 24 and parents of patients between the ages of 8 and 24. The primary outcome was the presence of any clinical or self-diagnosed mental health problem. The survey included information on cross-cutting disease factors such as disease duration, active disease status, current steroid medication, history of disease flare following remission, and appearance-altering comorbidities (such as psoriasis, stretch marks, alopecia, skin ulceration, and visible scarring). The researchers also examined results by mental health problem (depression, anxiety, and self-harm/suicidal ideation). Overall, they found that certain rheumatologic disease factors, including those that alter appearance, are predictive of mental health problems such as depression or anxiety. The findings will help identify targets for mental health screening in youth with rheumatologic diseases.

New Juvenile Idiopathic Arthritis Quality Measure Set for the Pediatric Rheumatology Care and Outcomes Improvement Network

A team that included HSS pediatric rheumatologist Nancy Pan, MD, reported highlights of new quality measures for the treatment of juvenile idiopathic arthritis. The study also provided information about the performance of these new measures, which were created by the Pediatric Rheumatology Care and Outcomes Improvement Network. The measures take into consideration clinical health importance, scientific validity, and feasibility, as well as best practices. They include both clinical evaluations based in part on the clinical Juvenile Arthritis Disease Activity Score and patient-reported outcomes such as pain, physical function, and overall well-being. An analysis of the new measures found that they are feasible for use on patients with juvenile idiopathic arthritis and can help to maximize quality improvement efforts and optimize the delivery of care.

“CVD risk has long been known to be elevated in SLE, especially among young patients, and remains the leading cause of death,” said lead study author Medha Barbhaiya, MD, MPH, an assistant attending rheumatologist from the Division of Rheumatology, Department of Medicine, Barbara Volcker Center for Women and Rheumatic Diseases at HSS and Weill Cornell Medical College. “However, unlike in DM, another chronic disease associated with premature atherosclerosis, where aggressive protocols are in place to reduce CVD risk, no such guidelines for primary or secondary prevention of CVD exist for patients with SLE. We aimed to quantify the risk of CVD in patients with SLE compared to those with DM and the general population.”

The researchers compared CVD risks of patients with lupus, patients with DM and general population U.S. Medicaid patients. In this cohort study, the researchers identified age- and sex-matched (1:2:4) adults with SLE, DM or in the general population from Medicaid Analytic eXtract between 2007 and 2010. They collected baseline sociodemographic factors, comorbidities and medications. Cox regression models calculated hazard ratios of hospitalized nonfatal CVD events (combined myocardial infarction [MI] and stroke) and MI and stroke separately accounting for competing risk of death and adjusting for covariates. They compared risks in age-stratified models.

“Our results show that Medicaid patients with SLE had a higher nonfatal stroke risk and similarly high risk of MI as patients with DM. MI and stroke risks were over twice the risk in SLE patients aged 18 to 39 years compared to patients with DM in the same age group,” explained Dr. Barbhaiya.

In all, the researchers identified 40,212 patients with SLE, 80,424 patients with DM and 160,848 non-SLE non-diabetes patients, of whom 92.5% were female, with a mean age of 40.3 (+/-12.1) years. Nonfatal CVD incidence rate per 1,000 person years was 27% higher in patients with SLE compared to patients with DM driven by excess risk in the 18 to 39 category (patients had 2.22 times the risk). Patients with SLE had 2.67 times higher risk of CVD compared to the general population.

“Despite a lower prevalence of traditional CVD risk factors, SLE patients had higher nonfatal stroke but similar MI risks as DM patients. MI and stroke risks were over twice the risk in SLE patients aged 18 to 39 years compared to their DM counterparts,” said Dr. Barbhaiya. “Our results suggest that early and aggressive CVD screening and better means of personalized CVD risk stratification and modification are needed for SLE patients. Additionally, future studies identifying the underlying mechanism of the observed excess CVD risk in SLE patients, particularly in younger patients between ages 18 to 39, are warranted.”

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.

"During the last decade or so, accumulating data has consistently demonstrated a strong association between cigarette smoking and rheumatoid arthritis risk, particularly for seropositive RA, with an interaction between smoking and underlying genetics," says Medha Barbhaiya, MD, MPH, rheumatologist at HSS.

Using the Nurses’ Health Study, Dr. Barbhaiya found current smoking was strongly related to risk for the subtype of SLE associated with anti-double-stranded DNA+.

"Although further studies are needed in this area, the idea that rheumatic disease may be modifiable by behavior change, such as quitting smoking, may provide hope to patients who otherwise feel resigned there is no way to change their disease risk," Dr. Barbhaiya says.

Read the full article at The-Rheumatologist.org.

According to Dr. Barbhaiya, African American patients with lupus had a 34 percent increased risk for any stroke, while Hispanic patients had a 25 percent increased risk.

"Whereas risk of stroke shows substantial sociodemographic variation in the general U.S. population, little is known about racial/ethnic variation in risk of ischemic and hemorrhagic stroke and specific risk factors among SLE patients," noted Dr. Barbhaiya and her team of researchers.

"Further research confirming the current findings and investigating factors such as genetics, biomarkers, lifestyle factors such as diet and physical activity, medications, and other thrombotic risk factors is needed," they added.

Read the full article at medpagetoday.com.

She interviews Medha Barbhaiya, MD, MPH, rheumatologist at HSS, who explains that SLE is known to disproportionate affect non-white populations in the U.S.

"Future SLE research among racial and ethnic groups should consider the role of diversity in genetic factors, biomarkers, lifestyle and physical activity, other thrombotic risk factors, and socioeconomics among various subpopulations. [Studies should also] evaluate potential gene-environment interactions in relation to outcomes. In addition, the relationship between barriers to healthcare access and long-term outcomes related to SLE need to be further investigated among non-white populations in the United States," says Dr. Barbhaiya.

Read the full article at RheumatologyAdvisor.com.

HSS rheumatologist Michael D. Lockshin, MD, and director of the Center, shared his conversations with patient Barbara Volcker, wife of former U.S. Federal Reserve Chairman Paul Volcker. According to the article, Mrs. Volcker met Dr. Lockshin in the 1970s to treat her rheumatoid arthritis.

"She was the type of patient that I really enjoyed taking care of because she challenged me on everything. She would say, 'But that answer doesn't make sense. Give me the information behind it. Convince me.' She drove me to question my own assumptions to respond to her," said Dr. Lockshin.

In the late 1990s, Mrs. Volcker's health worsened, and the Volckers offered to establish a center at HSS to honor her. Dr. Steven Paget, who was physician in chief at HSS, and Dr. Charles Christian, who was the emeritus physician in chief, invited Dr. Lockshin, then acting director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), to discuss the center's mission, and he was ultimately offered the job as director, a position he still holds.

The Center was established in 1997. Mrs. Volcker passed away the following year at the age of 68.

"Her questions are the core of the Center that bears her name," noted Dr. Lockshin.

The Center convened a conference on the biology of sex differences in autoimmune illness—the first of its kind—within a year of opening its doors, notes Dr. Lockshin. The topic later gained national attention for all human health when the Institute of Medicine (later renamed the National Academy of Medicine) convened a committee to address the same question and published a report in 2001, according to Dr. Lockshin, who served on the committee. Doruk Erkan, MD, MPH, a rheumatologist at HSS whose early research focused on antiphospholipid syndrome, joined the Center in 2005 as physician-scientist.

Today, the Center is marking 20 years of research and clinical work devoted to women with various rheumatic conditions. According to Dr. Lockshin, physicians at the Center see more than 3,000 individual patients for issues of pregnancy and contraception, antiphospholipid syndrome, and other rheumatic illnesses.

As part of the Center's research, HSS rheumatologists Jane E. Salmon, MD and Lisa R. Sammaritano, MD are co-investigators of a study on hormone treatment in lupus as well as pregnancy in lupus patients.

Additionally, HSS research associate Mikhail Olferiev, MD received a grant from the center to study the expression of genes across health donors and patients with lupus. "I hope that my study will contribute to a better understanding of an autoimmune disease and possibly identify new therapeutic targets," Dr. Olferiev said.

HSS scientist Theresa T. Lu, MD, PhD also received a grant to study whether fat tissue might influence stromal cells in lymph nodes to contribute to sex differences in rheumatic diseases.

Dr. Lockshin explained that concepts and ideas about pregnancy and issues related to women with rheumatic diseases have changed over time in part because of research discoveries coming out of HSS.

Additionally, the Center recently welcomed a new member, HSS rheumatologist Medha Barbhaiya, MD, MPH. Dr. Barbhaiya explained that she joined HSS because of the Center's strong emphasis on clinical care and clinical research related to lupus, antiphospholipid syndrome, and pregnancy in rheumatic diseases.

Several of its members hold leadership positions associated with the Center's mission, according to Dr. Lockshin. For example, Dr. Erkan chairs both the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking, headquartered at the Center, and the 15th International Congress on Antiphospholipid Antibodies. Kyriakos Kirou, MD, conducts lupus nephritis clinical trials, and Dr. Sammaritano chairs the ACR Reproductive Health Guideline Project. With a background in environmental causes of autoimmune illnesses, Dr. Barbhaiya is involved with the ACR. In addition, Dr. Lockshin served on committees with a focus on pregnancy, sex differences, and other aspects of autoimmune illness and he is past editor in chief of Arthritis & Rheumatism (now Arthritis & Rheumatology).

In a phone interview, Mr. Volcker said that he is delighted with the Center's accomplishments over the years. Furthermore, he said he is sure if Mrs. Volcker were alive she would be "very pleased and happy that her name was attached to it, no doubt in my mind".

Read the full article at the-rheumatologist.org. This also appeared in the January 2018 print issue.