RA Drugs Increase Flesh-Eating Strep Risk!?;Back to Running After Femoral Neck Stress Fractures; Women STILL Vastly Underrepresented in Orthopedics

RA Drug Connection to Flesh-Eating Strep!?

You had me at “flesh-eating.”

A team of scientists from the University of California San Diego School of Medicine has shown that rheumatoid arthritis (RA) patients taking medications that inhibit interleukin-1beta (IL-1beta) are 300 times more likely to contract invasive group A Streptococcal (GAS) infections than patients not on the drug! On the upside, the researchers have shown that IL-1beta serves as the body’s early warning system for bacterial infections.

Victor Nizet, M.D., a professor at University of California San Diego School of Medicine, told OTW, “Our laboratory research had indicated that mice with genetic defects in IL-1beta signaling were very susceptible to group A strep infection. We then treated normal mice with one of the common IL-1beta inhibitor drugs used to treat rheumatoid arthritis, anakinra, and found they also experienced more severe necrotizing skin infections. That led us to the FDA adverse event reporting website to calculate ‘proportional reporting risk, ’ whereupon we found that patient’s receiving IL-1beta blocking drugs were reported to have experienced serious group A strep infections at a dramatically higher rate than patients receiving any other drug in the database. Then back to the lab, where our research uncovered that IL-1beta is capable of detecting group A strep directly (not via inflammasomes), which overturned some standing assumptions about the function and evolution of the innate immune system.

“GAS ‘flesh-eating disease’ necrotizing fasciitis is a devastating bacterial infection involving the skin, subcutaneous and deep soft tissue, and muscle, with rapid bacterial growth to spread along the fascial sheaths that separate adjacent muscle groups. Invasive GAS diseases may also result in the development of toxic shock syndrome: a ‘cytokine storm’ produced in response to GAS superantigens that substantially increases the risk of death due to hypotension, widespread organ dysfunction and disseminated intravascular thrombosis. Early surgical intervention with debridement and potential fasciotomy is critical.

“If the orthopedic surgeons and nurses are involved in the care of patients with rheumatoid arthritis or other disorders taking IL-1beta inhibitor and potentially other anti-cytokine therapy, they should recognize that such patients are likely more prone to invasive streptococcal infection and to a more rapid and sever course of disease, and thus be vigilant.

“Our basic science studies suggest that other drugs that are currently in development to target other parts of the IL-1 pathway, without inhibiting receptor function, may not be associated with a similar risk of serious GAS infection.

“Pain out of proportion to superficial signs of infection can be a clue to underlying necrotizing fasciitis. Penicillin and clindamycin is the preferred antibiotic regimen, and intravenous immune globulin might be considered if there is suspicion of toxic shock syndrome.”

Back to Running After Femoral Neck Stress Fractures

Researchers from Spaulding Rehabilitation Hospital, Harvard Medical School, and Massachusetts General Hospital have addressed a question that few others have…‘When can a runner with a femoral neck stress fracture get back to running?’

The team looked at 27 such fractures in 24 runners who had a mean age of 32.9 years in an effort to determine if the grade of femoral neck stress fractures based on MRI correlated with return to running (RTR) time. All fractures were compression sided; no patients underwent surgery. Images were graded from 1 to 4 using the Arendt stress fracture severity scale.

Lindsay Ramey, M.D., is with the Department of Physical Medicine and Rehabilitation at the Spaulding Rehabilitation Hospital in Boston. Dr. Ramey told OTW, “I share an interest in high-risk stress fracture management with Dr. Kelly McInnis, the senior author and one of my mentors. We were starting to see more femoral neck stress fractures among runners in her sports clinic, particularly in the spring prior to the Boston Marathon, and every patient asked the same question: ‘When can I run again?’ We found some data to help predict recovery time for more common stress fractures but femoral neck stress reactions were rarely, if ever, included in these studies, making it difficult to answer this question. Anecdotal, it seemed to be quite variable among patients. Dr. McInnis really brought this question to my attention and, from there, we just tried to answer the question.

“Once diagnosed, the first stratification point in the treatment of femoral neck stress fractures is location/type of injury. While superolateral, tension-sided femoral neck stress injuries often require surgical intervention, inferolateral, compression-sided injuries can typically be managed conservatively with a period of restricted weight bearing followed by a graded return to activity. Many clinics, including our own, use pain as a guideline to advance through this progression; however, this can result in variable, unpredictable time out of activity, which is quite difficult for the athlete.

“As seen with other types of stress fractures, our findings suggest that low grade (grade 1) injuries can typically return to running more quickly than higher grade (grade 3 & 4) injuries, averaging 7.4 weeks for grade 1 injuries and increasing with each grade to 17.5 weeks for grade 4 injuries in our study. While this is based on a small sample size at a single site, it is the first published study looking at return to running time based on femoral neck stress fracture grade of injury and can serve as a resource in helping to answer the common question, When can I run again?’

“Given the smaller sample size, identifying additional variables associated with return to running time was limited in this study. Despite this, a trend was identified between BMI [body mass index], injury grade and return to running time. Individuals with a BMI in the underweight category more commonly suffered from high grade (grade 4) injuries and, independently, showed a trend toward a longer return to running time. This suggests that counseling to correct or prevent low weight and ensure adequate energy balance, particularly among female runners, may be a helpful initiative to decrease severity of injury and time out of running. Further, assessment for abnormal menses is an important indicator for energy imbalance among female athletes. Patient education regarding the importance of sufficient energy for bone healing, particularly in the setting of the micro trauma that occurs during running, is paramount.”

Females Still Vastly Underrepresented in Orthopedic Surgery

There is still stagnation when it comes to females entering the orthopedic surgery profession, says a new study from the University of Minnesota and Yale School of Medicine. The team examined data for all ACGME-accredited [Accreditation Council for Graduate Medical Education] orthopedic surgery residency training programs in the U.S. (2009-2010 through 2013-2014). During the time period of 2004 to 2009, the mean percentage of female trainees in U.S. orthopedic surgery residency programs was 11.6%, and during the time period of 2009 to 2014, this mean percentage increased to 12.6%.

Ann Van Heest, M.D. is the Director of Education with the Department of Orthopaedic Surgery at the University of Minnesota and was a co-author on this study. She told OTW, “I had done a previous study looking at the percentage of women residents in orthopedics in 2004-2009, and wanted to repeat it now looking at 2009-2014. We wanted to see whether orthopedics had improved in the number of women resident trainees.

“Orthopedic surgery lags behind all other surgical subspecialties in training women. Women orthopedic surgery residents have remained at less than 15% of all trainees for the past ten years. Most women medical students make the decision to pursue orthopedic surgery based on rotations during medical school. Better mentorship during medical school and greater female faculty representation would improve female representation in our profession. Improving the culture to be inclusive of female trainees is essential.

“If women are choosing to be urologists and cardiac surgeons at a greater rate than choosing to be orthopedic surgeons, we need to take a hard look at the culture that we create in orthopedic surgery. About 15% of ACGME accredited programs in the United States continue to train few or no women. Pressure on these programs to add diversity to our profession is needed. Achieving diversity has been shown to provide more perspectives for effective decision-making, more innovation and creativity for organizations, and greater understanding of the patient population that we treat.”