RA is a chronic disease characterized by inflammation in the synovium, the tissue that covers the inner surface of the joint cavity. Although usually accompanied by joint pain, swelling and deterioration, the level of inflammation varies from patient to patient, potentially requiring customized treatment plans. “What is surprising to us is that there are some patients who have clinical remission, yet continue to experience pain and show radiographic progression of the disease with high levels of synovial inflammation, while others have high disease activity with many swollen and tender joints and little inflammation in the synovial tissue” said Susan M. Goodman, MD, rheumatologist at HSS and principal investigator of the study. She explained that even when standard tests suggest the disease is under control, the joint fluid can still show high levels of inflammation. “By analyzing synovial fluid characteristics, we expected it might give us some insight into the disparity between disease progression and apparent remission,” she added.

The team analyzed samples from 64 patients with RA, 90.6% of whom were women, and with a median age of 65.3 ±11.7 years. The physicians collected synovial fluid samples to analyze and compare with the synovial tissue biopsy counterpart, which defines the inflammatory profile of the disease.

Dr. Goodman and the team measured the total white blood cell count, as well as the percentage of neutrophils, lymphocytes and monocytes in each synovial fluid sample. They then compared those findings to two additional key pieces of clinical information: the patient’s disease activity (such as joint swelling, pain, etc.) and the level of inflammation seen in the tissue.

Their analysis revealed that the total white blood cell count in the synovial fluid did not correlate with disease activity, however, the counting of individual cell types gave insights into tissue inflammation. As such, a higher percentage of neutrophils was associated with increased inflammation in the tissue, while a higher percentage of monocytes was associated with lower inflammation in the tissue.

Because the white blood cell counts in synovial fluid provided distinct and different information from standard disease activity measures and correlated well with tissue inflammation, the team believes it could help guide the selection of personalized anti-inflammatory therapies more efficiently.

“Synovial fluid extraction is already a routine part of care, but until now, it has never been used to analyze disease state in this way,” explained Dr. Goodman. In other words, the approach could be adopted without placing additional burden on healthcare providers.

"It's important that we're gaining new methods of investigating patients with RA,” Dr. Goodman added, “since choosing the appropriate therapy and choosing it in an efficient way is clearly the best way to achieve the best outcomes.”

According to Dr. Goodman, the next phase of this study, led by HSS rheumatologists Melanie H. Smith, MD, MPH, and Dana Orange, MD, MS, will look at both the proteomics and genetics of the cells within the fluid with more molecular and immunologic techniques, with the goal of finding even more clinically relevant and important information.

Poster details

Title: Can synovial fluid features be used to predict synovial tissue pathotype?

Authors: Susan M. Goodman, Michael Parides, Solana Cushing, Daniel Ramirez, Edward DiCarlo, Rebecca B. Blank, Laura Donlin, Anna Helena Jonsson, Amit Lakhanpal, Bella Mehta, Dana Orange, Melanie Smith.

Abstract n°: 2057

Presentation: June 12^th, 2025. 2:45 PM CEST

“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.

The study examined how patients engage with the digital world using real-time data from Google Trends. The patterns reveal not only how rheumatoid conditions affect daily life, but also reflect patients’ digital behavior as they turn to online resources for answers and support.

“Our work provides a clearer view of what patients are actually searching for and enables us to address their needs more effectively,” says Bella Mehta, MBBS, MS, MD, rheumatologist at HSS and senior author of the study.

Researchers selected a range of keywords and topics related to symptoms and treatment of rheumatic diseases. They found that online searches for symptoms consistent with rheumatoid or inflammatory arthritis, such as joint pain and swollen hands, spiked between 5:00 am and 7:00 am, when patients are likely at peak discomfort. In contrast, searches for medications like methotrexate, which is one of the standard medications for RA, were higher at night. This indicates that patients are actively seeking relief after experiencing pain throughout the day and into the evening.

“By identifying the times when patients most frequently experience and seek relief for their symptoms, we can optimize medication schedules and enhance patient support to provide more targeted care,” says Dr. Mehta. “This personalized approach not only improves the effectiveness of treatments but also helps patients better manage their conditions.”

This data-driven approach also fosters better communication between patients and providers, opening the door for more-informed discussions about symptom patterns and treatment options. “This allows us to be more responsive to patients’ needs and offer interventions that align with their daily challenges, leading to better health outcomes,” explains Dr. Mehta.

For example, many people with rheumatoid diseases search for dietary advice or other alternative treatments online, yet this is a conversation that rarely happens during clinical visits. Research studies like this can help bridge these gaps, creating more opportunities for physicians to talk to their patients about appropriate care options, rather than patients relying on potentially ineffective or harmful information online.

“By paying attention to these online behaviors, we can reduce the disconnect between the healthcare system and the individuals we serve, ensuring that we provide more empathetic, timely, and patient-centered care,” says Dr. Mehta.

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). 

According to Cynthia A. Kahlenberg, MD, MPH, an orthopedic surgeon at HSS and a coauthor of the study, TKA is rarely performed in patients under 21 years old but may be done in this population due to conditions such as inflammatory arthritis or juvenile idiopathic arthritis (JIA), malignant or non-malignant tumors, or trauma. However, the number of patients under the age of 21 undergoing TKA in the U.S. is unknown. In one of the largest U.S. studies of an institutional arthroplasty registry, only 19 TKAs were performed in patients under the age of 21 out of approximately 30,000 primary TKAs over 34 years—a majority of which were for JIA.

The researchers retrospectively analyzed the Kids’ Inpatient Database (KID), a national weighted sample of all inpatient hospital admissions of patients under 21 years old in approximately 4,200 hospitals in 46 states. The researchers used International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes to identify patients undergoing TKA from 2000-2016 and determine primary diagnosis. Descriptive statistics such as means and percentages, along with their 95% confidence intervals (95% CI), were calculated using the appropriate sample weights as recommended by the Agency for Healthcare Research and Quality for use with the KID dataset.

The total weighted number of TKAs performed in patients younger than 21 from 2000-2016 was 1,331; the number of TKAs performed per year in this age group remained relatively stable. The mean age of patients undergoing TKA was 14.8 years (95% CI, 14.4-15.2); 48.8% of the cohort was female. Among tumor patients, a higher proportion identified as Hispanic (22.1%) or other race (12.6%) compared to the non-tumor cohort; 70.3% of TKAs were performed for a primary diagnosis of a tumor; and the number of TKAs for malignant tumors increased slightly over the study period. In contrast, use of TKA for inflammatory arthritis / JIA decreased by more than 70% over the study period, likely due to improvements in medical management of inflammatory arthritis / JIA patients. The majority of TKAs were performed in urban teaching hospitals and in facilities with a large bed size, which likely reflects the complexity and rarity of these procedures.

“This was one of the first studies to take an in-depth look at TKA in this very young population,” said Dr. Kahlenberg. “Our study was able to confirm that tumors were the most common reason for knee arthroplasty in this population.”

“I think the biggest takeaway as a rheumatologist is that we are doing a good job treating these patients and over the years the treatments for inflammatory arthritis are really working well in this young population,” said Bella Mehta, MBBS, MS, rheumatologist at HSS and senior study author.

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

Bella Mehta, MBBS, MS, a rheumatologist at HSS and lead author of the study, presented the results today at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress in Copenhagen. “Lupus is a chronic autoimmune disorder that often affects women in their childbearing years,” explained Dr. Mehta. “In our previous work, we demonstrated that over the years, maternal and fetal mortality in lupus patients have improved significantly, and that was very reassuring to patients. However, less was known about morbidity. We set out to evaluate and quantify the indicators of fetal and maternal morbidity in women with lupus compared to those who did not have the disease.”

Using retrospective data from the National Inpatient Sample database, the researchers identified delivery-related hospital admissions from 2008 to 2017. Fetal morbidity indicators included preterm delivery and intrauterine growth restriction. Twenty-one indicators of severe maternal morbidity were identified and defined as unexpected outcomes of labor and delivery that result in significant short- or long-term consequences to a woman’s health.

Among the 40 million delivery-related hospital admissions, 51,161 patients were reported to have lupus. These patients were more likely to be older than women who did not have lupus (30.1 years versus 28.2 years), to be African American (25% versus 15%), and to receive Medicare (5% versus 1%).

During delivery, women with lupus were 15 times more likely to develop acute renal failure than those who did not have lupus (1.5% versus 0.1%), four times more likely to develop a cerebrovascular disorder (4.8% versus 1.1%), and nearly four times more likely to require a blood transfusion (4.0% versus 1.1%). Women with lupus were also more likely to develop cardiovascular and peripheral vascular disorders (1.1% versus 0.1%).

In terms of fetal morbidity, mothers with lupus were twice as likely to deliver prematurely (14.5% versus 7.3%) and nearly three times more likely to experience growth restriction in the womb compared to pregnant patients without lupus (8.0% versus 2.7%).

“The number of co-existing health conditions in pregnant women with lupus was much higher compared to women who did not have lupus. It seems likely that these comorbidities are responsible – at least in part – for the increased risk of fetal and maternal morbidity in lupus patients,” Dr. Mehta said. “It is noteworthy that a large percentage of deliveries by women with lupus were at large hospitals and urban teaching hospitals, reflecting the complexities of managing these patients.”

Dr. Mehta continued, “Our study is not meant to discourage women with lupus from getting pregnant. We believe our findings can help both patients and their physicians to assess risk, establish appropriate interventions and ensure that a multidisciplinary medical team is in place to counsel patients and manage their care.”

Authors: Bella Mehta, MBBS, MS, Katharine Kayla J. Glaser, Deanna Jannat-Khah (HSS), Yiming Luo (National Institutes of Health, Medicine, Bethesda), Lisa R. Sammaritano, MD, Jane E. Salmon, MD, Susan M. Goodman, MD (HSS), Fei Wang (Weill Cornell Medicine).

Between 2000 and 2016, the number of total hip arthroplasty (THA) procedures performed in patients under 21 years of age increased from 347 to 551, while the total pediatric population in the United States remained stable, the researchers found.

Traditionally, most young patients undergoing THA suffer from developmental bone or joint ailments or juvenile inflammatory arthritis. However, the new study revealed that the upswing in THA procedures in young patients is not being driven by a rise in the number of children with inflammatory joint disease, suggesting that nonsurgical therapies to control these conditions are working, said Bella Mehta, MBBS, MS, MD, a rheumatologist at HSS and the senior author of the study.

“Our study shows that although THA procedures are increasingly being performed in young people, we aren’t seeing more of these patients seeking surgery for inflammatory arthritis,” Dr. Mehta said. “We’re doing a better job at treating these individuals so they don’t develop end-stage joint damage. Twenty years ago, we didn’t have access to effective pharmacologic treatments for these conditions, and now we’re using them well and helping these patients live a better life.”

“These procedures are still pretty rare in hospitals, and some surgeons might not see any young patients,” added Alex Gibbons, a research assistant in Dr. Mehta’s group and a co-author of the study. “Although some site-specific data on THAs in adolescents exist, it wasn’t known how frequently these procedures were being performed in the United States and if that frequency was growing or not.”

For the study, Dr. Mehta and her colleagues used the Kids’ Inpatient Database, a repository of information on patients under 21 years of age from approximately 4,200 hospitals in 46 states. The researchers looked for elective and non-elective primary THA procedures.

The mean age of young patients undergoing THA was just over 17 years and remained constant throughout the duration of the study. Most patients were white (55.3%) and had private insurance (56.5%). The majority (80%) of THAs were performed in urban teaching hospitals.

Mark P. Figgie, MD, chief emeritus of the Surgical Arthritis Service at HSS and a co-author of the study, said the finding that most THA procedures in young patients are performed in urban and teaching hospitals reflects a trend that is beneficial for these patients. As other studies have demonstrated in conditions like inflammatory arthritis, when hip replacements are performed by surgeons with significant experience, patients have better outcomes. “And for younger patients, the nuances require the expertise and knowledge to avoid complications and optimize outcomes,” Dr. Figgie said.

The most common diagnoses for young patients undergoing THA were osteonecrosis, osteoarthritis and juvenile idiopathic arthritis (JIA)/inflammatory arthritis, the researchers found. Over the course of the study, the frequency of THA for osteonecrosis rose from 24% to 38%, while that for arthritis fell from 27% to 4%—likely a reflection of recent improvements in medical management for the condition, they added.

Dr. Figgie noted that improvements in implant technology and materials have made the devices far more durable than they were 20 years ago. As a result, surgeons now feel more comfortable offering THA to young patients because their implants are likely to withstand the wear and tear of decades of activity.

Dr. Mehta said the findings could be of value both to clinicians and young patients, for whom, in many cases, the surgery is their first major operation. “I would use these results to say to a young person: ‘There are a lot of people who get these procedures; you’re not alone.’ I find that, especially for young patients, knowing they’re not the only ones to experience something really helps. And it’s a life-changing procedure for them.”

“We’re happy to see pregnancy outcomes improved over time in all of the groups studied, however improvements were more evident in some groups than others,” said lead study author Bella Mehta, MBBS, MS, MD, a rheumatologist at HSS. “African Americans and Hispanics continue to have poor pregnancy outcomes. Further study is warranted to determine where resources are needed to improve access and care for these patients.”

In the new study, researchers used the National Inpatient Sample (NIS) to conduct a retrospective cross-sectional analysis of lupus and pregnancy related hospital admissions from 2008 to 2017. The NIS is the largest publicly available all-payer healthcare database designed to produce US regional and national estimates of inpatient utilization, access, cost, quality and outcomes. Patients with lupus were identified by using ICD-9/10 codes. The researchers evaluated the pregnancy outcomes of four groups: Caucasians, African Americans, Hispanics and Asians/Native Americans/Others. Outcomes included in-hospital maternal mortality, fetal mortality, non-delivery related admissions and Cesarean section (C-section).

The investigators found that from 2008 to 2017, there were a total of 61,012 SLE pregnancy related hospitalizations. The median age of pregnant women in the sample was 29 for African American and Hispanic women, 30 for Caucasians, and 31 for Asians/Native Americans/Others. African Americans and Hispanics were more likely to be on Medicaid (51% and 49% respectively) versus Caucasians (30%) and Asians/Native Americans/Others (33%).

During the 10-year study period, fetal mortality and non-delivery related admissions and C-section rates improved in all racial/ethnic groups. Maternal mortality rates were very low throughout the study period, with none observed among Caucasians. Overall fetal mortality declined in all racial/ethnic groups, with a numerically greater reduction in Hispanic (from 291 in 2008-2009 to 101 in 2016-2017 per 10,000 admissions) and Asian/Native American/Other (from 267 in 2008-2009 to no observations in 2016-2017 per 10,000 admissions) versus Caucasian (from 136 in 2008-2009 to 108 in 2016-2017 per 10,000 admissions) and African American (from 385 in 2008-2009 to 308 in 2016-2017 per 10,000 admissions). In the latest data from 2017, African Americans continued to have worse fetal mortality than Hispanic or Caucasian patients, and Asians/Native Americans/Others had the least fetal mortality. In data from 2017, African Americans had the most non-delivery admissions, followed by Hispanics, Asians/Native Americans/Others and Caucasians. In 2017, C-section rates were highest in African Americans, followed by Caucasians, Asians/Native Americans/Others, and Hispanics.

“We have learned over the years that patients with lupus can become pregnant but need to do so in a certain way. That is, they should have quiet disease activity at conception and they shouldn’t become pregnant if they have serious internal organ damage such as renal failure,” said study co-author Lisa R. Sammaritano, MD, a rheumatologist at HSS. “What this study shows is there is still a persistent disparity between non-Caucasian ethnic groups and Caucasians in terms of pregnancy outcomes in women with lupus, but both groups have had improvement over ten years.

“It’s good to see that improvements have been across racial and ethnic groups, but we need to continue to work toward identifying the reasons disparities still exist,” she continued. “This kind of large database study is very useful in looking at this type of problem across the country as a whole, rather than a study focused on a single hospital system, as most other studies do.”

Authors: Bella Mehta¹, Yiming Luo², Deanna Jannat-Khah³, Jiehui Xu⁴, Lisa Sammaritano³, Jane Salmon³, Michael Lockshin¹, Susan Goodman³ and Said Ibrahim⁵. ¹Hospital for Special Surgery, Weill Cornell Medicine, New York, NY, ²National Institutes of Health, Bethesda, MD, ³Hospital for Special Surgery, New York, NY, ⁴Weill Cornell Medicine, New York, NY, ⁵Weill Cornell Medicine, Cleveland, OH.

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.

“In our retrospective analysis, we found the utilization rate of bilateral knee replacement was much lower in African American patients compared to white patients,” said Bella Mehta, MBBS, MS, a rheumatologist at HSS. “On the other hand, although African Americans having unilateral knee replacement have been shown to have higher in-hospital complication rates compared to white patients, this pattern was not consistent for bilateral knee replacement during the time period we studied.” She presented the findings on November 9 at the virtual American College of Rheumatology annual meeting.

Dr. Mehta and colleagues compiled information from the National Inpatient Sample (NIS)- Healthcare Cost and Utilization Project (HCUP) database from 2007 to 2016. They looked at trends in utilization and major in-hospital complication rates of unilateral versus bilateral knee replacement nationwide in patients age 50 and older.

Investigators assessed racial differences over time, adjusting for age, sex and comorbidities; hospital variables, including hospital volume, number of beds, region and teaching status; and community level factors, such as median household income.

From 2007 to 2016, 5.5 million unilateral and 276,000 bilateral knee replacements were performed in the United States. The percentage of bilateral knee replacements declined from 5.53% in 2007-08 to 4.03% in 2015-16.

The researchers found that African Americans were much less likely to undergo a double knee replacement compared to white patients during the years analyzed. In-hospital complication rates varied throughout the study period, with no significant difference between African American and white patients.

To explain the study findings concerning complication rates, Dr. Mehta said there could be a more rigorous patient selection process when considering candidates for same-day bilateral knee replacement. Regarding the lower number of African Americans having the bilateral procedure, she said physicians may be offering it less often to African American patients or they may be choosing not to have the procedure.

“Since the complication rate for bilateral knee replacement is not higher for African American patients, health providers should work to provide access to all appropriate patients,” Dr. Mehta said. She noted that future studies could take a closer look at the patient selection process or assess the role of an individual’s health insurance plan in utilization of the bilateral procedure.

“As we seek to achieve health equity for our patients, we must understand the challenges they face in accessing care, as well as variance in their outcomes,” said Michael L. Parks, MD, hip and knee surgeon at HSS and study author. “Our ultimate goal is to provide the same quality of care to everyone.”

Bella Mehta, MBBS, MS, a rheumatologist at Hospital for Special Surgery (HSS) in New York City, presented the findings at the American College of Rheumatology/Association of Rheumatology Professionals annual meeting on November 11 in Atlanta.

“With the aging of the population, elective total hip replacement has become one of the fastest-growing procedures to manage severe osteoarthritis,” said Dr. Mehta. “By 2030, the number of hip replacements is expected to reach 572,000 annually in the US. Medicare, the largest payer of joint replacement surgery, has introduced several payment reform models that target discharge destination and risk of hospital readmission after surgery. Our study examined how the socioeconomic status of the community in which one resides influences discharge destination and the odds of 90-day hospital readmission after hip replacement.”

Dr. Mehta noted that where a patient receives post-op care and rehab has a considerable impact on the total cost of hip replacement surgery. Previous studies have demonstrated significant variations in outcomes and costs due to individual factors such as race. There have been far fewer studies on the impact of community-level factors.

“Our study pushes the envelope by examining the role of where one lives in understanding variations in post-op care after elective joint replacement surgery. And it reflects the growing academic collaboration in clinical research between HSS and Weill Cornell Medicine investigators,” explained Said Ibrahim MD, MPH, MBA, senior investigator and chief of the Division of Healthcare Delivery Science and Innovation at Weill Cornell Medicine.

For the analysis, the investigators identified almost 85,000 patients in the Pennsylvania Health Care Cost Containment Council database who had elective hip replacement surgery between 2012 and 2016. The researchers used the Area Deprivation Index (ADI) from the American Census Survey, which reflects a geographic area’s level of socioeconomic deprivation and is associated with health outcomes.

In addition to discharge destination, the investigators assessed the risk of 90-day readmission for patients sent to a facility compared to those who received their post-op care and rehab at home. The researchers also assessed the interaction of race and ADI on outcomes.

The study found that patients from impoverished communities were more likely to be discharged to an institution compared to home after a hip replacement. The interaction effect of race and ADI on discharge destination was statistically significant in African American patients 65 years and older, but not in patients under 65 years old. The level of community deprivation did not have an effect on 90-day hospital readmission, nor did the interaction of ADI and race.

As a possible explanation for the study findings, Dr. Mehta noted that patients from impoverished communities may have less access to community-based services such as social support. Thus, discharge to a facility for post-operative and rehabilitative care might be perceived as a safer option in clinical decision-making.

“Our study is important because it advances our understanding of the relationship between health care and social determinants of health,” said Dr. Ibrahim. “Future studies should determine which specific community factors influence discharge destination and how they could be modified to allow more patients to go home after a hip replacement.”

Dr. Mehta added, “The ultimate goal of research is to design socially informed health policies to improve quality of care and outcomes.”

Susan M. Goodman, MD, and Michael L. Parks, MD, of HSS and Kaylee Ho, MS, of Weill Cornell Medicine were also involved in the study.

“The biggest take-home message from this study is that more lupus patients are attempting pregnancy, most of the physicians are not recommending against it, and women are having successful deliveries,” said lead study author Bella Mehta, MBBS, MS, an assistant attending physician at Hospital for Special Surgery and an instructor in clinical medicine at Weill Cornell Medicine, in New York City.

SLE is a systemic autoimmune disease, which affects 241 per 100,000 people in North America; it is predominantly diagnosed in women of childbearing age. Years ago, women with SLE were advised to avoid having children due to high rates of complications, including pre-eclampsia and eclampsia. In more recent years, studies have shown that pregnancy in women with SLE carries a higher maternal and fetal risk than does pregnancy in healthy women, but this is improving. Between 1960 and 2003, rates of miscarriages and other pregnancy loss decreased from 40 percent to 17 percent in women with lupus. In the last two decades, a new understanding of the pathophysiology of SLE, new medications, and guidelines for risk assessment and management of patients with lupus have improved outcomes in patients, but just how this has impacted pregnancy in these women was unclear.

To shed light on this issue, researchers from HSS, the Icahn School of Medicine at Mount Sinai, Weill Cornell Medicine and New York-Presbyterian/Weill Cornell Medical Center, all in New York City, turned to the National Inpatient Sample (NIS) database. The NIS contains discharge data from approximately 20 percent of all community hospitals in the United States. It is the largest all-payer inpatient database in the United States focusing on adult pregnant hospitalized women with and without SLE. Using this database, the investigators examined data for all pregnant women from 1998 through 2015, focusing on in-hospital maternal mortality, fetal mortality, preeclampsia/eclampsia, c-section, non-delivery related admission, and length of stay.

Among the findings, the researchers identified a dramatic decline in in-hospital mortality in SLE patients, 442 per 100,000 admissions for the years between 1998 and 2000 compared with <50 per 100,000 admissions for the years between 2013 and 2015. In-hospital mortality also declined for patients without lupus during the same time period, but not as dramatically, from 13 to 10 per 100,000 admissions. In other words, the increased risk for in-hospital mortality for patients with lupus fell from 34 times higher for the period between 1998 and 2000 to only 2.5-5 times higher for the period between 2013 and 2015. A decline in fetal mortality was also noted in patients with lupus and was larger than in patients without lupus, but the difference was not statistically significant.

“For lupus patients who are young and who are thinking of pregnancies, they should know that many other patients with lupus over the past two decades have successfully become pregnant and delivered, and mortality is minimal,” said Dr. Mehta. “This is encouraging for young women with lupus. If they decide to have children, they can. In the 1980s, there were clinicians who advised young women with lupus not to get pregnant because they were so worried about mortality. What this study proves is this is no longer applicable.”

Other findings from the study showed that preeclampsia/eclampsia rates decreased in patients with lupus during the two periods studied, from 9.5 percent to 9.1 percent, and increased in patients without lupus, from 3.3 percent to 4.1 percent. Hospital length of stay declined in lupus pregnancies, from a mean of 4.3 days to 3.8 days, but increased in non-lupus-pregnancies, from a mean of 2.5 to 2.7 days.

The percentage of lupus patients increased significantly from 0.9 percent to 0.16 percent in all pregnancy-related admissions and from 0.08 percent to 0.14 percent in delivery-related admissions. The researchers believe that as care for lupus has improved, more patients with the disease have attempted and succeeded in having healthy pregnancies.

Improved outcomes have likely been the product of better diagnosis and referral of patients with mild disease to rheumatologists, counseling of patients to attempt pregnancy when disease is quiescent, and improved therapies for lupus and lupus-associated pregnancy complications. Other factors improving outcomes include continuation of hydroxychloroquine throughout pregnancy and use of low dose aspirin and heparin for patients with antiphospholipid syndrome (APS), a condition that is common in lupus patients and associated with miscarriages and fetal loss.

“Lupus is a disease that largely affects women and most particularly women of color,” said senior author Dr. Said Ibrahim, chief of the Division of Healthcare Delivery Service and Innovation, senior associate dean for diversity and inclusion and professor of healthcare policy and research at Weill Cornell Medicine. “While our study couldn’t thoroughly examine race and income disparities in lupus pregnancy outcomes, the findings support the concept that improving quality of care for all patients is one way to address inequities in healthcare. It is a hopeful message.”

“Besides mortality, complications that clinicians worry about in women with lupus, such as preeclampsia, have also decreased in the past two decades. The times are changing,” said Dr. Mehta. “I think physicians should be aware of this, so they can advise patients and give them the right sort of guidance. It is okay for women with lupus to get pregnant, as long as they are under the care of a rheumatologist and high risk obstetrics.”

Within HSS, the Lupus and Antiphospholipid Center of Excellence provides individualized, state of the art care, support and education to patients with lupus and APS, including pregnant women with the disease. The Center centralizes patient care and research with the goal of improving the quality of life for all lupus and APS patients.

“There is very little known about Still’s disease,” said lead author Bella Mehta, MBBS, MD, MS, rheumatologist at Hospital for Special Surgery, in New York City. “When clinicians see a patient who is Asian with intermittent fevers and rashes, try to think of Still’s disease. If you don’t think about it, you are never going to diagnose it. Still’s is a rare, heterogenous disease, so every patient presents slightly differently, and it is difficult to diagnose. It has to be on your radar, if you are ever going to diagnose it.”

Adult Onset Still’s Disease is characterized by intermittent spiking high fevers, arthritis or arthralgia, and an evanescent (lasting less than 24 hours) maculopapular skin rash. AOSD remains a mystery on many fronts. While both genetics and infectious triggers have been suggested to play a role, the etiology of AOSD remains unknown. The disease is complex and associated with high morbidity and mortality. Complications of the disease including Macrophage Activation Syndrome, Disseminated Intravascular Coagulation (DIC) and Thrombotic Thrombocytopenic Purpura are life threatening.

AOSD is estimated to impact 0.16-0.4 per 100,000 persons and little epidemiological data on the disorder exists. Most available data comes from single centers or a single geographic region. There are no large-scale studies in the United States describing the demographics, complications or mortality in patients with the disease.

To help fill the knowledge gap, researchers led by Dr. Mehta set out to describe the demographics of U.S. hospitalized patients with AOSD, the morbidity and complications leading to mortality, and the risk factors associated with adverse outcomes in patients. The investigators used retrospective data from the 2009-2013 Nationwide Inpatient Sample (NIS) database, the largest publicly available all-payer inpatient care dataset in the United States. This database contains discharge data from approximately 20% of nonfederal, short-term, general and other specialty hospitals in the United States. Using NIS, the researchers identified all patients 18 years and older with a primary diagnosis of AOSD from 2009 to 2013. To minimize misclassification bias, they excluded patients with a concurrent diagnosis of rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, polymyalgia rheumatica, ankylosing spondylitis, inflammatory myopathies, or systemic sclerosis.

Dr. Mehta and colleagues identified 5,820 patients admitted for AOSD in hospitals across the United States between 2009 and 2013. The average age was 53.6 years and 65.6% were females. The majority of patients, 56%, were white, 3% were Asian, and 31% were African American, Hispanic or other. Race was not identified for 10% of patients. Roughly 40% of patients were hospitalized in urban teaching hospitals, and 42% were admitted in large volume hospitals. In the sample, 1.7% were diagnosed with Macrophage Activation Syndrome, 1.1% had Disseminated Intravascular Coagulation, and 0.4% had Thrombotic Thrombocytopenic Purpura.

The mortality rate was 2.6% in hospitalized AOSD patients, and the mean age of these patients was 62.4. Asians were 6.39 times more likely to die in the hospital compared with whites. “The finding that Asians were much more likely to die was important; the disease is more prevalent in Southeast Asia,” said Dr. Mehta. “Asians seem to have a different intensity of the disease.”

Dr. Mehta said clinicians need to be thinking more about Still’s. “Sometimes it takes months and months for a patient to even get to a rheumatologist with suspected Still’s disease,” said Dr. Mehta. “More awareness of the disease would lead to more diagnosis.”

The researchers also found that older age increased mortality and for every increase in the number of medical conditions, the odds of in-hospital mortality increased by 20%. Patients who developed Disseminated Intravascular Coagulation were 30 times more likely to die in the hospital.

“Older age increases mortality for most other diseases too, so that was not an uncommon finding, but if you have an older person with a lot of comorbid conditions with Still’s disease, you need to be much more vigilant,” said Dr. Mehta. She said that DIC should be a red flag for clinicians. “Patients with Still’s disease who have Disseminated Intravascular Coagulation have really bad outcomes, so watch for signs and symptoms of this, adjust the expectations of the patient and family, and start treating aggressively at the first sign of DIC,” said Dr. Mehta.

While prospective studies of Still’s would be ideal to get a firm grasp on the disease, said Dr. Mehta, the new study, with one of the largest cohorts of Still’s disease patients, is the best data available so far. “Before this study, we did not have any idea of Still’s disease patients in the U.S. and predictors of worse outcomes,” she said. “Now, at least in the U.S., we know that Asians have worse outcomes and so do patients who have Disseminated Intravascular Coagulation.”

The study appears in the January 31, 2019 issue of BMC Musculoskeletal Disorders.

Co-author Bella Mehta, MBBS, MD, a rheumatologist at HSS, explains the thinking behind the study and its results to OTW, "Previous research has identified individual-level social risk factors such as race, gender, or education that may result in poor outcomes after total knee arthroplasty (TKA). Community characteristics like poverty may also affect TKA outcomes."

"We found that pre-op and two-year post-op WOMAC pain and function scores were between 2.75-4.88 WOMAC points worse (on 100-point scale) in neighborhoods with a high immigrant proportion (≥ 40%) compared to low immigrant proportion (<10%). However, these differences were small, and not statistically significant after multivariable analyses," Dr. Mehta adds.

Read the full article at RyOrtho.com.

"Beginning in the 1980s, and especially in the 1990s, many studies identified specific risk factors for pregnancy complications and proposed best-practice management guidelines. We wished to see whether these advances improved pregnancy outcomes for SLE patients," said Dr. Mehta.

The findings were presented at the American College of Rheumatology (ACR) Annual Meeting on October 22, 2018.

Read the full article at consumer.healthday.com.

Dr. Mehta presented her research findings at the 2018 North American Young Rheumatology Investigator Forum in Destin, Florida.

"There is a lack of robust epidemiological data on AOSD due to its rarity, with an estimated incidence of 0.16 to 0.4 per 100,000 patients…. There are no large-scale studies of this in the United States," said Dr. Mehta.

"This is the first large-scale study in the United States to report epidemiological outcomes of Still's disease, and it is the largest," she added.

Study data concluded that patients of Asian ethnicity had 6.4 times the risk of inpatient death and patients with intravascular coagulation concurrent had 30 times the risk.

Read the full article at healio.com [registration required].