Stem Cells for Tendonitis Study at HSS…and More

Key Stem Cell Tendon Study at HSS

The labs at Hospital for Special Surgery (HSS) are humming these days, as clinician scientists delve into soft tissue healing…specifically, in the identification of cell based approaches. Scott Rodeo, M.D., co-chief of the Sports Medicine and Shoulder Service at HSS tells OTW, “We have a rat model of tendonitis where we are evaluating the role of stem cells in improving the structural changes in the tendon. Thus far we have learned that these implanted cells do have the ability to modify tissue. Next, we will determine how to direct the cells to act like a tendon cell. We need to find out the exact signals needed to push the cells down the appropriate pathway. We are seeing that these cells have a positive role in improving the structural and biomechanical properties.”

“Our team is poised to begin a meniscus repair model in rabbits which we will ultimately transfer to humans. We are also looking at the initial feasibility of using bone marrow derived cells for the improvement of rotator cuff healing in humans. We will take a sample of cells that we use in each patient and look in the lab and measure the cell concentration and specific cell surface markers. The fact of the matter is that we don’t truly know what these cells are. We call them stem cells, but we don’t know how accurate that is. It’s also not yet clear how well they proliferate in cell culture. There appears to be tremendous variability in the behavior of these cells between different individuals.”

“Then there is the other side of the equation, namely, the effect of mechanical loading on these tissues. How the cells behave may depend on the mechanical load on the cells. We are doing ACL reconstructions in rats where we use an external fixator on the knee, and control the knee’s motion and ligament loading. Thus far we have found that excessive or early post-op motion is likely to have a detrimental effect on healing. We are excited by the fact that this has tremendous clinical applicability.”

Disaster Certification: Are You Ready?

While “help” is not a dirty word, heading into a disaster zone unprepared can get you—and the people you are trying to assist—into loads of trouble. To avoid such scenarios, the American Academy of Orthopaedic Surgeons (AAOS), the Orthopaedic Trauma Association (OTA) and the Society of Military Orthopaedic Surgeons (SOMOS) have developed a certification process and database for orthopedists who want to respond to disasters. Christopher Born, M.D., chief of Orthopedic Trauma at Rhode Island Hospital within the Department of Orthopaedic Surgery of Brown University, updates us on the status of this program. “This project emanated from our experiences in Haiti, where we found that despite good intentions, many surgeons didn’t know what they were getting into. It became clear that some major issues could best be addressed through an educational program. These include working with the government/military as well as Nongovernmental Organizations (NGOs), the organization of disaster response, personal safety and security as well as ethical/cultural considerations when treating people in an austere environment.”

“To date the disaster preparedness course has been given three times, with the fourth session planned for the AAOS meeting next month [March 19-23] in Chicago. A total of 179 participants have attended the course and the one scheduled for March is full at 75 attendees. Of this pool, AAOS has started the first responder database and thus we now have a ‘bank’ of 130 surgeons willing and properly trained to do disaster work.”

“One of our goals is to educate surgeons as to what they might expect…what to bring, what not to bring, etc. Doctors have to be physically fit, and know the ins and outs of their personal liability. Their malpractice insurance may not cover this work; the same is true of their life insurance and disability insurance. Then there are the proper immunizations, i.e., those required by government teams.”

“We are encouraging orthopedic surgeons to get involved with some of the government disaster response teams like Disaster Medical Assistance Teams (DMATS) or the Department of Health and Human Services’ (HHS) IMSuRT team. Unfortunately, the government is still not well organized in terms of incorporating civilian responders into the military or HHS for the purposes of surge coverage in the event of a national or international disaster. The AAOS, OTA, and SOMOS continue to work on a number of levels to move the ball downfield toward pre-credentialing surgeons in order to work with government teams. Frankly, this may require some sort of legislative action. The educational programs that have been enacted by the orthopedic professional organizations may help to ease some of the government’s fears of incorporating civilians in the disaster response programs. By setting an example, it is also hoped that other professional medical organizations will also actively engage their memberships in this type of activity.”

Pass on Small Clots?

Clot size does differ, but what to do with the smaller ones? Paul Tornetta, III, M.D. is a professor, vice chairman, and residency program director in the department of orthopaedic surgery at Boston University School of Medicine. He is also director of orthopaedic trauma for the Boston Medical Center and a former president of the OTA. He tells OTW, “The sizes of pulmonary emboli (PE) vary, with smaller, subsegmental clots having a much lower pulmonary risk than larger lobar or central clots. With advent of the CT pulmonary angiogram we are seeing many more PE being diagnosed…but most of this increase are smaller sized clots. There are multiple papers in the literature showing that the rate of PE is increasing but death from PE is not. This has been termed “overdiagnosis” due primarily to the diagnosis of very small and possibly clinically irrelevant clots. Some of these are likely normal anatomic variants that are being called subsegmental PE.”

“At present there is not much agreement as to what to do with these small clots, and while there is some data suggesting that they are not dangerous most physicians are immediately responding by aggressively anticoagulating patients. This approach carries its own risks, primarily that of increased bleeding, which may lead to other complications, including death.”

Yelena Bogdan, M.D., a PGY3 resident at Boston University Medical Center, led a multicenter evaluation looking at the complication rates in orthopedic trauma patients who were diagnosed with a PE. She states, “Our team has examined data from multiple trauma centers, looking at DVT prophlaxis, the tests used to diagnose PE, the treatment instituted and the complications of both the PE (pulmonary) and the treatment (bleeding, infection, etc.). We found that all of the centers are responding similarly and are performing very aggressive anticoagulation irrespective of the size of the clot. Interestingly, the complication rate of the anticoagulation was 12%; these rates were the same regardless of the size of the clot, but the pulmonary complications varied. The bigger the clot the worse the pulmonary complications.”

Dr. Tornetta added, “This work is essentially a snapshot of how trauma centers are diagnosing and treating PE. Based on this review, we have a better idea of the risks of aggressive anticoagulation. However, we don’t yet know the true risk of using a different protocol. We will approach our next study in a prospective manner with careful monitoring. We have formed a committee on this topic and they are taking a hard look at how to most appropriate way to proceed. Perhaps we will choose one anticoagulant for a trial and only address subsegmental clots as a first measure. No one center sees a lot of these, meaning that we would need multiple centers. But wouldn’t it be great if we found that anticoagulation wasn’t necessary in some cases…then we could eliminate certain risks for some patients.”

Patent Alert: Statins for Tendonitis

High cholesterol could be a real drag on your tendons, says a shoulder surgeon from the Rothman Institute in Philadelphia. Joseph A. Abboud, M.D. is an orthopedic surgeon at Rothman, as well as an associate professor of Orthopaedic Surgery at Thomas Jefferson University Hospital. He tells OTW about their news. “We recently had a patent approved for the application of cholesterol lowering agents—statins—for the treatment of patellar tendon injury. Through work done at the University of Pennsylvania, Louis J. Soslowsky, Ph.D. and I have demonstrated an association between elevated cholesterol and tendon disease. In mice, rats, pigs, and monkeys we have shown altered tendon mechanical properties; we are also seeing altered tendon healing properties in animals exposed to high cholesterol diets versus animals on a regular diet. We believe intrinsic changes happen over the lifetime of a tendon leading to its degeneration and possibly ultimate failure. One of the factors that predisposes a tendon to degenerative processes may be years of elevated cholesterol. In the near future, we are looking to initiate a clinical trial looking at the use of cholesterol lowering agents for the prevention of tendon injury.”