JBJS Reviews Editor’s Choice–Genomics in Reconstructive Orthopaedic Surgery
In current clinical practice, most patients who undergo total joint replacement surgery receive similar preoperative, intraoperative, and postoperative management. However, despite similar care, there is wide variability in terms of outcomes and satisfaction. This variability may be due to a lack of understanding of the genetic basis of degenerative joint disease.
Genomics, the scientific study of genes and their interrelationships with each other and the environment, has gained increased attention in the most recent decade. With the completion of the Human Genome Project in 2003, genomic research has surged, ushering in new genetic technologies and opportunities in health care. Indeed, genetic tests have been developed to identify mutations for complex diseases such as breast, colon, and ovarian cancer. These examples are but a few of the ways in which genomics can impact human disease and its prevention.
The term personalized medicine has been coined by clinicians and researchers to capture the concept that a patient’s genetic profile will determine appropriate therapy. By understanding the importance of genetics and the environment in shaping clinical outcomes, the future of medicine has the potential to provide more individualized care.
In orthopaedics, the application of genomics has centered on osteoarthritis, osteoporosis, rheumatoid arthritis, and oncology. In adult patients who undergo joint replacement surgery, the use of biomarkers and genetic testing may aid in preventing postoperative complications.
As noted above, in adult reconstructive surgery, there is a high degree of variability in patient outcomes (including complications and overall satisfaction). The key to understanding the cause of such varied outcomes may well lie in our understanding of the genetic basis of degenerative joint diseases and the genetic response to treatment. A number of conditions that occur in patients undergoing adult reconstructive orthopaedic surgery may be modifiable through the use of genomics and our understanding of them. Examples include infection, thromboembolism, heterotopic ossification, arthrofibrosis, hyperalgesia, osteolysis, and osteonecrosis. In the April 2016 issue of JBJS Reviews, Elbuluk et al. discuss the future of “orthogenomic” research, the goal of which is to establish patient-specific strategies for optimizing results and expectations after adult reconstructive surgery.
Although the application of genomics in orthopaedic practice remains limited, the framework to identify practical interventions has begun to be constructed. The ability to obtain genetic information may allow joint arthroplasty surgeons to preoperatively stratify patients according to risk on the basis of their genetic profile and establish patient-specific strategies that will optimize results after surgery. Large population-based studies will need to be conducted in order to allow orthopaedic researchers to build the necessary database to identify these genes and their biomarkers. The advent of 21st-century personalized care of orthopaedic patients undergoing total joint replacement surgery is beginning to be realized, and the future looks promising.
Thomas Einhorn, Editor
JBJS Reviews
Not So Run-of-the-Mill Running Injuries
Lower-extremity stress fractures account for an estimated 16% of all injuries among runners. The April 2016 “Case Connections” article sprints forward from an April 13, 2016, Case Connector report about a stubborn running-related stress fracture of the inferior pubic ramus that did not respond to the usually successful conservative approach.
It’s often challenging for orthopaedists to make a diagnosis in a patient group in whom multiple musculoskeletal injuries or ailments may exist. Patients with suspected stress fractures may have radiographs with subtle, easily overlooked findings. A bone scan and/or other advanced imaging are often required to make a definitive fracture diagnosis.
Continued running due to a missed diagnosis or a patient’s ardent noncompliance can culminate in complications that may eventually require surgical intervention. The best outcomes are perhaps achieved in a setting that fosters strong collaboration between the surgeon, patient, physiatrist, and/or physical therapist with expertise in the mechanisms and physiology of running.
In a postscript to this Case Connections article, JBJS Case Connector co-editor Tom Bauer, MD describes his fateful experience with a calcaneal stress fracture while running the 2013 Boston Marathon.
Cobalt-Ion Thresholds Could Ease Follow-Up Burden on Some MoM Patients
In the mid-2000s, before the orthopaedic community was aware of the potentially catastrophic shortcomings of metal-on-metal (MoM) hip implants, nearly half of all hip replacements used MoM components. With so many people walking around today on those prostheses, orthopaedists are looking for rational and effective ways to monitor these patients for adverse reactions to metal debris.
Findings from a diagnostic Level II study by Matharu et al. in the April 20 edition of The Journal of Bone & Joint Surgery will help identify patients who are at low risk of metal-debris adverse reactions, specifically among those who have Birmingham Hip Resurfacing (BHR) and Corail-Pinnacle MoM implants. The authors found that when measuring cobalt ions in whole blood, the optimal threshold for identifying adverse reactions to metal debris was 2.15 µg/L for BHR patients and 3.57 µg/L for Corail-Pinnacle patients. These implant-specific thresholds are lower than the non-implant-specific thresholds proposed by US and UK regulatory agencies, and in this study the cutoffs had good sensitivities and specificities, and their negative predictive values exceeded 98%.
The authors say identifying low-risk individuals will allow orthopaedists to focus surveillance efforts on patients who are at higher risk of adverse reactions to metal debris. They even suggest that patients below the implant-specific thresholds for cobalt could be excluded from regular follow-up regimens, provided they have normal clinical examinations and radiographs.
While lauding Matharu et al. for prospectively determining these thresholds, commentator Lawrence Dorr, MD says these findings need “to be tested at multiple centers to validate [their] superiority,” and he emphasizes that better methods to identify asymptomatic patients who are at high risk of adverse reactions to metal debris still must be developed.
What’s New in Hand Surgery
Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all OrthoBuzz Specialty Update summaries.
This month, OrthoBuzz asked Sanjeev Kakar, MD, the author of the March 16, 2016 Specialty Update on hand surgery, to select the five most clinically compelling findings from among the more than 30 he cited in his article.
Wrist Trauma
–In the treatment of distal radius fractures, is volar plating superior to closed reduction and pin fixation? A prospective randomized trial of 461 adults with acute dorsally displaced distal radial fractures that were amenable to closed reduction found no clinically significant differences in Patient-Rated Wrist Evaluation (PRWE) scores among those who underwent percutaneous wire fixation and those who underwent locking-plate fixation. The findings led the authors to conclude that when looking at functional outcomes, treatments other than plate fixation may suffice.1
–Authors of a cost and utility analysis of 268 patients with a surgically treated distal radial fracture concluded that the routine use of radiographs made at two weeks postoperatively is of little clinical benefit, except in cases of patients with high-energy intra-articular fractures or those who sustain an injury after surgery.2
Wrist Arthritis
–To challenge conventional dogma that the contralateral wrist of rheumatoid arthritis patients who undergo wrist arthrodesis must maintain motion in order for them to perform activities of daily living, a long-term study followed 13 bilateral wrist arthrodesis patients for an average of 14 years. The major functional limitations noted were turning a door knob and opening a tight jar lid. Increasing age, preoperative corticosteroid use, and concomitant shoulder or elbow disorders were associated with worse outcomes. Ninety-three percent of the patients expressed satisfaction and said they would repeat the bilateral procedure.3
Carpal Tunnel Syndrome
–Should one perform staged or simultaneous carpal tunnel surgery? A cost-effectiveness study of simultaneous versus staged bilateral carpal tunnel release in 198 patients found that those who underwent simultaneous surgery had significantly fewer days off work and fewer postoperative follow-up visits, and they also incurred significantly lower costs in terms of mean amounts billed and fees collected.4
Trapeziometacarpal Joint Arthritis
–Is there an optimal suspension arthroplasty for the treatment of basilar thumb arthritis? A randomized controlled trial of 79 patients with trapeziometacarpal arthritis found that functional/clinical outcomes at 12 months were essentially the same between a group that underwent ligament reconstruction and tendon interposition (LRTI) and a group that underwent trapeziectomy and flexor carpi radialis weave around the abductor pollicis longus tendon. The notable exception was an improvement in PRWE scores at three months among those who underwent the LRTI procedure.5
References
- Costa ML, Achten J, Parsons NR, Rangan A, Griffin D, Tubeuf S, Lamb SE;DRAFFT Study Group. Percutaneous fixation with Kirschner wires versus volar locking plate fixation in adults with dorsally displaced fracture of distal radius: randomised controlled trial. BMJ. 2014;349:g4807. Epub 2014 Aug 5
- Stone JD, Vaccaro LM, Brabender RC, Hess AV. Utility and cost analysis of radiographs taken 2 weeks following plate fixation of distal radius fractures. J Hand Surg Am. 2015 Jun;40(6):1106-9. Epub 2015 Mar 31.
- Wagner ER, Elhassan BT, Kakar S. Long-term functional outcomes after bilateral total wrist arthrodesis. J Hand Surg Am. 2015 Feb;40(2):224-228.e1. Epub 2014 Dec 13.
- Phillips P, Kennedy J, Lee T. Cost effective analysis of simultaneous versus staged bilateral carpal tunnel release. Read at the American Association for Hand Surgery Annual Meeting; 2015 Jan 21-24; Paradise Island, Bahamas. Paper no. 104.
- VermeulenGM, Spekreijse KR, Slijper H, Feitz R, Hovius SE, Selles RW.Comparison of arthroplasties with or without bone tunnel creation for thumb basal joint arthritis: a randomized controlled trial. J Hand Surg Am. 2014 Sep;39(9):1692-8. Epub 2014 Jun 10.
Nebulous Controls, Noncompliance Mar JAMA Low Back Pain Study
OrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Brett A. Freedman, MD, in response to a recent JAMA study on treatment for chronic low back pain.
Chronic low back pain (CLBP) is truly a bio-psycho-social disease. Cherkin et al. in the March 22/29, 2016 issue of JAMA published a randomized clinical trial comparing the performance of two psychologically focused interventions for CLBP with usual care.
The authors randomly assigned 342 subjects solicited from an integrated health plan in the state of Washington who had at least 3 months (average 7.3 years) of nonspecific CLBP to one of three cohorts: mindfulness-based stress reduction (MBSR), cognitive behavioral therapy (CBT), or usual care. MBSR is a pain self-management program that incorporates yoga and focuses on “increasing awareness and acceptance of moment-to-moment experiences.” The two therapy arms included eight 2-hour sessions.
The primary and secondary outcomes were computed values on patient-reported outcome (PRO) instruments compared from baseline out to one year. According to intention-to-treat analysis, MBSR and CBT resulted in a significantly higher chance of patients obtaining a clinically meaningful response, which equated to a >30% improvement in scores on the modified Roland Disability Questionnaire at 26 weeks after enrollment (61% for MBSR vs. 58% for CBT vs. 44% for usual care).
While these findings are interesting and support the notion of more research into non-pharmacological and non-interventional CLBP treatment, the impact of this study is limited by inherent flaws. The investigators’ intent was to have the usual care group represent a control group. However, the usual care cohort was far from controlled. At the time of enrollment, those randomized to the usual care cohort were each given $50 and were set free to “seek whatever treatment [for their CLBP], if any, they desired.” The resultant placebo effect of receiving active treatment (i.e. MBSR, CBT) versus no prescribed treatment (i.e. usual care cohort) is substantial.
Also, aside from reporting their collected PRO data, the authors say little about what happened to the usual care group during this trial, further making this cohort too nebulous to serve as a meaningful comparator. If this cohort is excluded from the analysis, this becomes a negative-findings study, since there were no significant differences in any measured outcome between the MBSR and CBT cohorts, aside from mental health measures, which were significantly improved following CBT.
Another major flaw is the very high rates of patient noncompliance with treatment. Only 51% of the subjects in the 2 therapy arms attended at least 6 of the sessions, and 13 subjects (11%) in each of the active-therapy groups attended no sessions. A substantial minority of patients failed to meaningfully participate in their prescribed intervention, yet their improved outcomes are attributed to the impact of these programs. If the same lack of adherence to protocol occurred in a pharmacological or surgical study, the results would be ignored and the article would likely go unpublished, or at least not published in a high-impact journal such as JAMA.
In conclusion, the greatest merit of this study is the research question it poses. We certainly need more work on this subject, but unfortunately this particular study does little to further advance our understanding of the best practices for approaching the bio-psycho-social disease we call CLBP.
Brett A. Freedman, MD is an orthopaedic surgeon specializing in spine trauma and degenerative spinal diseases at the Mayo Clinic in Rochester, MN.
“Mortgages” for Medical Care: A Good Idea?
OrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Chad Krueger, MD, in response to a report about healthcare loans that aired recently on Boston radio station WBUR.
How much is life-altering or life-saving treatment worth? People and the companies that insure their health are likely to have different answers to this difficult question. The same person may even have different answers at different points in his or her life. Because our ability to care for patients sometimes outpaces individual and societal economic resources, additional hypothetical dilemmas arise: Would you cash in everything you owned to help your child overcome an illness? What if you had two children with the same life-threatening condition but only had enough money for one of them to get treatment?
On the surface, the idea of commercial lenders granting mortgage-like loans to either individuals or insurance companies to pay for expensive treatments sounds reasonable. Such loans would spread out payments over five to ten years and, under a plan broached by Boston oncologist David Weinstock and MIT finance professor Andrew Lo, would protect borrowers from having to pay for treatments that do not work.
The example in the WBUR story focused on a very expensive hepatitis-C medication, but it begs many additional questions: For example, how would a lender decide whether a loan application for a specific treatment would be too risky? The WBUR story included comments by Boston College Law School professor Patricia McCoy, who noted that the home-mortgage market collapsed in 2008 largely because both lenders and borrowers were unable—or unwilling—to properly determine risk. How would that borrower-lender risk-assessment psychology play out in life-or-death healthcare situations, especially when the annual percentage rates for some of the healthcare credit cards currently available can exceed 25%?
Even if they come to pass, healthcare “mortgages” will not solve the underlying problem of having more medical and surgical options available than we, as a society, have the resources to pay for. Healthcare loans may help some people get the care they need, but ultimately they would do nothing to reduce the cost of care. Still, if we continue working hard to reduce healthcare costs, I think discussions about new and interesting ways to pay for healthcare should be encouraged.
Society may never be able to answer the question of how many dollars a certain treatment is worth, but questions about the costs (economic and emotional) of not being treated can be even harder to answer.
Chad Krueger, MD is a military orthopaedic surgeon at Womack Army Medical Center in Fort Bragg, NC.
For an in-depth look at healthcare loans, read this article in Science Translational Medicine.
JBJS Classics: Sarmiento Pioneered Weight-Bearing Fracture Healing
OrthoBuzz regularly brings you a current commentary on a “classic” article from The Journal of Bone & Joint Surgery. These articles have been selected by the Editor-in-Chief and Deputy Editors of The Journal because of their long-standing significance to the orthopaedic community and the many citations they receive in the literature. Our OrthoBuzz commentators highlight the impact that these JBJS articles have had on the practice of orthopaedics. Please feel free to join the conversation about these classics by clicking on the “Leave a Comment” button in the box to the left.
Prior to the innovative work of Gus Sarmiento in the 1960s, most orthopaedic surgeons treated tibial shaft fractures with a prolonged period of immobilization, in a long-leg non-weight bearing cast. While the fracture usually healed, knee joint stiffness and atrophy of the entire limb usually resulted as well.
In this 1967 JBJS classic, Sarmiento extended the concept of early weight-bearing treatment of these fracture as advocated by Dehne and others by incorporating the limb in a below-the-knee total-contact plaster cast, a technique that had recently been developed for the early rehabilitation of a below-the-knee amputation. The skin-tight plaster cast was applied over a single layer of stockinette one to two weeks after the acute swelling had subsided. It was molded proximally to contain the muscles of the proximal leg, and it had medial and lateral condylar flares, similar to a patellar-tendon-bearing (PTB) prosthesis.
Sarmiento encouraged early weight bearing in the cast, as he believed that doing so stimulated fracture healing. His confidence was borne out by this report of 100 consecutive tibial shaft fractures treated with a PTB cast. All 100 fractures healed, and healing occurred with minimal deformity or shortening. This success soon led to Sarmiento’s development of a functional below-the-knee tibial fracture brace made of Orthoplast®, a thermoplastic material which, when heated in a water bath, could be molded easily to the injured limb.
While today most tibial shaft fractures are treated with intramedullary nails, the principles developed by Sarmiento still apply, as the nail acts much like the fracture brace to maintain alignment during the healing process. Fracture healing is enhanced by weight bearing, and joint stiffness and muscle atrophy are avoided by early motion.
Sarmiento’s concept of functional treatment was later extended to the treatment of humeral and ulnar shaft fractures, which commonly continue today to be managed effectively with fracture braces that he developed. This emphasis upon early functional restoration while the fracture is healing has allowed many patients to achieve faster healing and to resume full function much sooner.
James D. Heckman, MD
JBJS Editor Emeritus
Marathon Bombing Anniversary: Reflection, Gratitude, Hope
Three years ago today, the 2013 Boston Marathon was stolen from the athletes and the city by two terrorist bombs, which led to four deaths and hundreds of injuries. In March 2014, in conjunction with our friends at the Journal of Orthopaedic and Sports Physical Therapy (JOSPT), JBJS published It Takes a Team, a special report on the emergency preparedness, long-term care, and outcomes for many of those caught up in the Marathon bombings. This report is available online for free.
Not a single bombing victim who reached a hospital alive on April 15, 2013 died, a stunning result of years of preparation and teamwork. It Takes a Team provides a behind-the-scenes look at how the level 1 trauma centers involved that day ensured that their staffs had the emotional backing, resources, and systems in place so they could focus on their seriously injured patients.
As runners and spectators prepare for the 2016 Boston Marathon, we remember those we lost, those who survived, and the countless number of people who are helping those affected face the future with hope and dignity. We also thank the many people whose dedication to disaster-preparedness helps ensure that the 2016 and forthcoming Boston Marathons will go on.
Jason Miller
Executive Publisher, JBJS
JBJS Webinar: Managing Complex Proximal Humeral Fractures
Proximal humeral fractures are the third most common occurring fracture in patients over the age of sixty-five years. These fractures are often difficult to accurately classify, and they can also be challenging to treat surgically.
On Tuesday, April 19, 2016 at 8:00 pm EDT, a complimentary webinar, hosted by The Journal of Bone & Joint Surgery, will present findings from two recent JBJS studies that explore the classification and treatment of complex proximal humeral fractures.
Milton Little, MD will examine whether 3D CT imaging helps orthopaedic surgeons classify proximal humeral fractures, and Derek J. Cuff, MD will analyze findings from a study that compared reverse total shoulder arthroplasty with hemiarthroplasty for treating these fractures in elderly patients.
Moderated by JBJS Deputy Editor Andrew Green, MD, the webinar will also feature commentaries on the study findings from shoulder experts Michael J. Gardner, MD and J. Michael Wiater, MD. The last 15 minutes of the webinar will be devoted to a live Q&A session.
Radiology Reports—Helpful or Annoying?
OrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Carola van Eck, MD, PhD, in response to an item about radiology reports posted on KevinMD.com by radiologist Saurabh Jha, MD.
As orthopaedic surgeons, we commonly seek consultation from our radiologist colleagues in cases where a diagnosis may not be obvious after a thorough history and physical examination, or when we’re seeking imaging confirmation of a diagnosis about which we’re quite certain. But we sometimes get frustrated when the radiology report includes phrases such as “clinical correlation recommended” or “cannot exclude malignant process,” as Dr. Jha notes in his KevinMD blog post. A related annoyance occurs when the radiology report lists a slew of differential diagnoses ranging from an ingrown toenail to cancer. Matters get even more difficult if our patients see and read a vague, ambiguous radiology report and come to our office anxious because they think they might have cancer.
But perhaps the main reason we surgeons can become annoyed by these reports is that they frequently state the obvious, and we may therefore interpret the reports as being condescending and patronizing. Informing the ordering orthopaedist that “the CT scan of the cervical spine is negative for fractures” is helpful, but reminding him or her that “CT does not exclude ligamentous injury” is not. I would like to think that such comments are not intended to be insulting, but they could very well be attempts by the radiologist to deflect professional liability. In his post, Dr. Jha reminds us bluntly that “the radiology report is a legal document.”
Regardless, if I am clinically concerned enough to order chest imaging on a post-op total hip patient who has been slow to get up for physical therapy and continues to require 2 liters of supplemental oxygen, a report that says “subsegmental pulmonary embolism cannot be entirely excluded with absolute certainty; please correlate with clinical findings” is not very helpful, because the clinical correlates are what prompted the order in the first place.
If you—like I did—thought that this frustration goes unnoticed by radiologists, it does not. Dr. Jha’s post refers several times to The Radiology Report, a book by radiologist Curtis P. Langlotz. Among many other recommendations, Dr. Langlotz (who was Dr. Jha’s attending at Stanford) admonishes his colleagues to report in a standardized fashion, to take a stand, and to use “normal” instead of “unremarkable.” Ultimately, I agree with Dr. Jha, who points out that medical decision making is all about taking a stand and that most of the time, it is better to be clear and wrong than vague and potentially not wrong.
Carola F. van Eck, MD, PhD is the chief resident physician in the Department of Orthopaedic Surgery at the University of Pittsburgh Medical Center.
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