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Mesenchymal Stem and Disc Degeneration Disease / Source: Wikimedia Commons, Robert M. Hunt and Nephron

Cell Therapy for DDD; Joint Replacement Risk Unpredictable?; Open Fracture Injection Insight

Elizabeth Hofheinz, M.P.H., M.Ed. • Tue, February 14th, 2017

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Cell Therapy for Disc Degeneration: Timing Likely Important

In the January 23, 2017 edition of the Journal of Orthopaedic Research, scientists from the Feinstein Institute for Medical Research at Hofstra Northwell School of Medicine discuss their research on the use of mesenchymal stem/stromal cells (MSCs) for the treatment of disc degeneration disease (DDD).

Lead researcher Nadeen O. Chahine, Ph.D., associate professor at the Feinstein Institute, explained the purpose of the study to OTW; “Stem cell therapy for degenerated discs and associated back pain is a promising yet complex therapy. Degenerate discs are not created equal—the environment in which you inject stem cells could very much impact the efficacy of the therapy. The specific environmental factors that affect efficacy are not yet fully understood, but our research provides evidence that the timing between disc injury and treatment can affect the cell’s ability to provide a therapeutic response.”

“Stem cells have the ability to migrate in the body after injection. It’s possible that migration of cells out of the disc could have deleterious effects (e.g., osteophyte formation) on vertebral surfaces. Careful consideration and optimization of the delivery method has to be considered for stem cell repair of the intervertebral disc.”

In the study entitled “Timing of mesenchymal stem cell delivery impacts the fate and therapeutic potential in intervertebral disc repair”, the authors wrote, the authors wrote, “This study used a rat disc stab injury model with administration of mesenchymal stromal cells (MSCs) at 3, 14, or 30 days post injury (DPI) to evaluate the impact of interventional timing on IVD (intervertebral disc) biochemistry and biomechanics. We also evaluated cellular localization within the disc with near infrared imagining to track the time and spatial profile of cellular migration after in vivo delivery.”

“Results showed that upon injection into a healthy disc, MSCs began to gradually migrate outwards over the course of 14 days, as indicated by decreased signal intensity from the disc space and increased signal within the adjacent vertebrae. Cells administered 14 or 30 DPI also tended to migrate out 14 days after injection but cells injected 3 DPI were retained at a significantly higher amount versus the other groups.”

“Correspondingly the 3 DPI group, but not 14 or 30 DPI groups, had a higher GAG (Glycosaminoglycan) content in the MSC injected discs. Enrichment of MSCs and increased GAG content in 3 DPI group did not lead to increased compressive biomechanical properties. Findings suggest that cell therapies administered at an early stage of injury/disease progression may have greater chances of mitigating matrix loss, possible through promotion of MSC activity by the inflammatory microenvironment associated with injury.”

Study: No Way to Predict Risk in Joint Replacements

Despite testing three different risk adjustment indices, researchers have found that none of them were useful in predicting readmissions among osteoarthritis (OA) patients who underwent joint replacement. The study, which appears in the January 2017 edition of Arthritis Care & Research, was led by Amit Kumar, Ph.D., a postdoctoral research associate at the Brown University School of Public Health. It is entitled, "Current Risk Adjustment and Comorbidity Index Underperforms in Predicting Post-Acute Utilization and Hospital Readmissions after Joint Replacements: Implications for Comprehensive Care for Joint Replacement Model."

One of the reasons for the study, as stated in the January 25, 2017 news release, is the new outcome based reimbursement environment. “To compel hospitals to do better, the Centers for Medicare and Medicaid Services (CMS) launched the Comprehensive Care for Joint Replacement (CJR) program in April 2016, which penalizes hospitals for readmission of joint replacement patients within 90 days.”

"In the absence of that risk adjustment, when sick patients have worse outcomes, hospitals will be penalized," said Dr. Kumar. "If we could find an index that was working for this population, we could recommend that—but unfortunately none of them are working very well."

Again, quoting directly from the press announcement; “Dr. Kumar and former colleagues at the University of Texas Medical Branch tested the applicability of the three industry-leading indices for predicting mortality and health care utilization: the Charlson Comorbidity Index, the Elixhauser Comorbidity Index and CMS's Hierarchical Condition Category.”

“Dr. Kumar analyzed Medicare data on every beneficiary who survived for 90 days after a total knee or total hip replacement performed because of osteoarthritis between January 2009 and September 2011. In all, the study covered a total of 605,417 patients. The data showed that 46.3% of patients were discharged home, 40.9% went to skilled nursing facilities and 12.7% stayed in inpatient rehabilitation.”

Amit Kumar told OTW, “Studies have shown that poor functional status is strongly associated with increased used of post-acute care services and hospital readmission. Current risk adjustment models contain extensive information on medical diagnoses, but not function-related measures. The missing information on physical functional status in claims data of older hospitalized patients can affect the decision-making process on discharge destination and continuity of care.”

“Orthopedic surgeons may improve service delivery by developing appropriate risk adjustment model and care transition plans based on patient functional status and initiating an intervention to prevent specific comorbid conditions associated with greater risk of readmission. The preventive measure can be initiated before and after surgery to address the medical needs of patients with high-risk of readmission.”

Institutional, Seasonal Variations in Infection Following Open Fractures

When it comes to infection after open fractures, does the incidence or organism vary with the season? Do they vary with the institution? A multicenter retrospective review, just published in the February 2017 edition of The Journal of Orthopaedic Trauma, included seven trauma centers distributed amongst the seven climates in the U.S. There were 5,127 patients with open extremity fractures. The review is entitled: “Institutional and Seasonal Variations in the Incidence and Causative Organisms for Posttraumatic Infection following Open Fractures.”

Principal investigator, Henry Claude Sagi, M.D., Professor of Orthopedic Surgery at Harborview Medical Center at the University of Washington in Seattle, told OTW, “There has been tremendous focus on ‘timing’ regarding infection following open fracture—timing of antibiotic administration, and timing of operative debridement.”

“Ostensibly, those variables could not be the only mitigating factors in determining the risk and causative organism for post-traumatic infection. In a country as large as the U.S. that has many different climatic regions and environmental conditions form one season to the next, it would seem logical that the season and region in which the injury occurs should have some influence on the incidence and bacteria involved in post-traumatic infection.”

“I think that we, as surgeons, have good evidence to help guide us in the treatment of open fractures when it comes to timing of debridement and antibiotic administration. What we don’t have is good evidence to support the continued use of a decades-old antibiotic prophylactic regimen that is applied to all patients with all injuries in all institutions—without regard to the region of the country, the environment, and the season in which the injury occurs.”

“This study, at the very least, suggests that there is substantial variation from one hospital to another and from one season to another for that particular hospital, and that the current standard for prophylaxis may be sub-optimal for all patients in all situations. Surgeons should speak with their local infectious disease specialists and audit their own practices to elucidate what organisms are most prevalent in their region, thus adjusting their prophylactic regimen accordingly.”

“Because this study was a retrospective review/audit, the data is clearly neither complete nor 100% accurate. While the denominator (total number of open fractures) from each institution is reliable, the numerator (number of infections) is subject to considerable bias secondary to poor follow up and patients being treated elsewhere for their infection. Variable follow-up and poor confidence in the numerator could lead to erroneous assumptions regarding both the incidence at a given institution and during respective seasons. We have recently initiated a nationwide multicenter prospective analysis with over 40 institutions (both level one and level two). Hopefully this will help to clarify the assumptions made in the previously published manuscript.”

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