Research and Publications
CREATES Study
Total Joint Center in Landmark Study
The term “brain fog” has surged in popularity with its prevalence among some COVID-19 cases. However, brain fog, or long-lasting changes in memory or thinking abilities, has long been known to occur in some older adults after major surgery.
Now, some eager and inquisitive surgical patients of the Total Joint Center are giving back to science by participating in a landmark study of brain health and recovery after surgery. The study, which goes by the acronym CREATES (Cognitive Recovery after Elective Surgery) is led by Lori Daiello, PharmD, ScM, research scientist at the Rhode Island Hospital Alzheimer’s Disease and Memory Disorders Center (ADMDC). Dr. Daiello has been studying brain aging for more than a decade.
The Total Joint Center has teamed up with Dr. Daiello to enroll adults aged 65 and older who are scheduled to have a major surgery. The five-year study will be enrolling new patients until January 2024.
“The CREATES study will help us further understand the cognitive effects of both general and spinal anesthesia in older patients undergoing total joint surgery and elective surgery in general,” said Eric M. Cohen, MD, hip and knee orthopedic surgeon at the Total Joint Center. “By enrolling in this study, research participants are helping to advance medicine and help future patients in need of a total joint replacement.”
The CREATES study uses a new type of MRI brain imaging technique, developed at USC to investigate whether blood-brain barrier (BBB) dysfunction precedes development of postoperative cognitive disorders. The BBB is an important natural line of defense that protects the brain from attack by infections and inflammation.
Dr. Daiello noted, “Normally, the BBB protects brain cells from harmful substances circulating in the blood. A ‘leaky’ or damaged BBB is likely to be an important risk factor for postoperative memory problems by permitting high concentrations of circulating inflammatory factors to flood the brain during the perioperative period.”
Patients who volunteer for this study will be followed for a period of up to 18 months. “We all change cognitively as we age,” said Dr. Daiello. “This research will help us understand it and could stimulate development of interventions designed to prevent it from either occurring or getting worse.”
The CREATES study is funded by a $3.8 million grant from the National Institutes of Health (R01 AG058648).
Learn more about, and how to volunteer for, the CREATES study
Exploring a Molecule to Ease Arthritis
With degrees in both engineering and medicine, Derek Jenkins, MD, a hip and knee replacement specialist with the Lifespan Total Joint Center at The Miriam and Rhode Island hospitals, and assistant professor of orthopedic surgery at The Warren Alpert Medical School of Brown University, brings a multidisciplinary perspective to his work.
He and colleague Gregory Jay, MD, PhD, co-founder of the Lifespan Medical Simulation Center, are exploring the role of the molecule lubricin in the prevention and treatment of arthritis.
“Lubricin is an interesting molecule,” Dr. Jenkins said. “It’s a very slippery substance found in normal knees that may play a similar role to the way engine oil works in your car. Dr. Jay and I have had conversations over the years about looking at the potential effect of lubricin or the lack of lubricin in the development of hip and knee arthritis.” Dr. Jay is one of the world’s foremost experts on lubricin.
Their IRB-approved study is exploring the effect of this unique molecule on arthritis and could lead to the development of a novel new supplement that could be injected into a patient’s painful joint to potentially prevent arthritis from progressing or, if possible, from developing at all.
Dr. Jenkins’ clinical practice and intuitive interest in how things work along with Dr. Jay’s successful patents and pending patent applications for technologies that could treat joint issues are an example of the interdisciplinary research underway at Lifespan. “While many studies involve the perfection of techniques and technologies, this study is examining a potential treatment to prevent the need for replacement in the first place,” Dr. Jenkins said.
Their study entails collecting synovial fluid and tissue, otherwise discarded, from patients undergoing knee and hip replacement surgery. The samples are then analyzed for molecular signatures of fibrosis which would be occurring in the synovium that is the lining of the joint capsule. Other studies have shown that lubricin prevents inflammation and may play a potent role in preventing synovial fibrosis which causes joint pain and stiffness. The production of lubricin decreases following joint surgery.
Dr. Jenkins reflected, “Lifespan is a fulfilling community where like-minded individuals can share ideas and work together in the care of patients, the development of new treatments for disease, and together, tackle problems yet unsolved.”
Research continues with potential for the discovery of a medical treatment to prevent arthritis and to improve the longevity of the joint once it has been replaced. This research is supported in part through the generosity of Kay and Leon Cooper.
PEPPER Study
Every year nearly one million total hip and knee replacements are performed in the United States.
As with any surgery, there is always a risk of post-operative complications. However, those who undergo hip and knee replacements are more susceptible to developing blood clots post-operatively.
To deal with the complications that blood clots can cause, many patients are put on blood thinners. While blood thinners solve the problem of clotting, they can also create another: bleeding. To combat the negative side effects of blood thinners, surgeons must balance the various risks.
A new study being offered to patients at the Total Joint Center at The Miriam Hospital, called “Comparative Effectiveness of Pulmonary Embolism Prevention after Hip and Knee Replacement (PEPPER),” aims to explore, compare, and identify which blood thinner currently on the marker is the best and safest to use.
The PEPPER trial will span five years and will include approximately 25,000 patients with the goal of identifying the best possible treatment for hip and knee replacement patients.
If you are interested in participating in the PEPPER study, please ask your orthopedic surgeon about how to enroll.
Pursuing the Promise of Anti-infective Joint Implants
Joint arthroplasty patients at The Miriam Hospital experience infections at a rate substantially below the national average, but even those few are too many for Valentin Antoci, MD, PhD, an orthopedic surgeon, researcher and assistant professor of orthopedics at The Warren Alpert Medical School of Brown University.
The hip and knee surgeon is pursuing avenues of research that will lead to better outcomes — both in the short and long terms — for patients treated at the Total Joint Center at The Miriam Hospital and beyond. Dr. Antoci’s research interests focus on “smart” joint implant design, tissue engineering, and biological interactions at the implant interface (such as coating titanium surfaces with the antibiotic Vancomycin to ward off infection).
In his research, Dr. Antoci collaborates with the Shukla Lab for Designer Biomaterials, headed by Anita Shukla, PhD, within the School of Engineering at Brown University. Engineering hydrogels for targeted delivery of antibiotics is among the lab’s pursuits. Dr. Antoci underscores the advantages of working across disciplines in “coming up with new solutions to problems.” The cross-pollination of ideas leads to novel approaches, he suggests.
Dr. Antoci also works with Christopher Born, MD, who heads the Diane N. Weiss Center for Orthopaedic Trauma Research at Rhode Island Hospital, and his collaborator, pharmacologist and microbiologist Dioscaris R. Garcia, PhD. Dr. Born’s research interests include the development of antimicrobial coatings for orthopedic trauma implants. His team also developed a rapid test to identify, during surgery, the bacteria causing an infection, allowing a more effective choice of treatment.
While these research endeavors are promising, Dr. Antoci emphasizes the importance of preventing infections in the first place. Taking steps in advance of surgery such as improving diet, quitting smoking, getting diabetes under control and losing weight, as well as using a special skin cleanser immediately before surgery, all contribute to a successful outcome.
Improving Surgical Results by Helping Patients to Reach Healthy Goals
In his study published in May 2016 in the Rhode Island Medical Journal “Modifiable Risk Factors in Total Joint Arthroplasty: A Pilot Study,” Dr. Jenkins reports his very promising results through helping patients improve their pre-operative risk before surgery and how that can improve their outcomes after surgery.
Dr. Jenkins was also recently published in orthopedic surgery’s most prestigious and highest-impact rated journal, the Journal of Bone and Joint Surgery, with his colleagues from the Mayo Clinic on techniques for complex Hip Revision Surgery. This is the second time that Dr. Jenkins has been published as first author in this prestigious peer-reviewed journal and this particular article “reports very important and useful information to the joint replacement community on the use of new technologies for hip revision surgery,” Jenkins says. The article titled “Minimum Five-Year Outcomes with Porous Tantalum Acetabular Cup and Augment Construct in Complex Revision Total Hip Arthroplasty” was Published in May 2017. “The good work that we all are doing here at the Total Joint Center for our patients is getting noticed on the National level. Being part of the teaching program at Brown University and involved in clinical research allows us to share our experience with the Orthopedic Community and contribute to the advancement of Science, Medicine, and Orthopedics. The end result is the most technologically-advanced, evidence-based care for our patients here in Rhode Island.”
Assistant Professor of Orthopedic Surgery at the Brown University Warren Alpert Medical School, Dr. Jenkins is actively involved in the education of Residents and Medical Students and was recently honored with a Brown University Certificate of Recognition for exemplary teaching “honoring teaching effort and dedication to the highest standards of teaching in the preclinical curriculum” as Course Leader in BIOL 3665 IMS II: Supporting Structures at Brown Medical School. His research interests focus on the incorporation of advanced techniques and technology in Joint Replacement Surgery including the direct anterior approach for minimally invasive hip replacement and is the Principal Investigator in multiple Research Review Board Approved Studies.
Dr. Jenkins, Dr. Antoci and the Lifespan Orthopedics Institute are also dedicated to Community Service through work with the Arthritis Foundation. For his work on the advancement of arthritis treatments, Dr. Jenkins was chosen as the Medical Honoree at the 2016 Rhode Island Walk To Cure Arthritis and Dr. Antoci will be the Honoree this year in 2017. The Orthopedics Institute has been a proud gold level sponsor at both events.
Publications
Derek Jenkins, MD was published in JBJS as first author on an important article reporting long-term outcomes of complex hip reconstruction surgery: Minimum Five-Year Outcomes with Porous Tantalum Acetabular Cup and Augment Construct in Complex Revision Total Hip Arthroplasty.