NYT Cites Hype of Stem-Cell Treatments for Joint Problems
An active, 71-year old man who declined joint replacement in favor of stem-cell treatment is quoted in a recent New York Times article as saying, “They’re really quick to try to give you fake joints and make a bunch of money off you.” But the NYT article goes on to suggest that making money may be the main objective of some of the many hundreds of clinics that have sprung up around the US to offer cell-based injections to people with aging or damaged joints who want relief without surgery.
The article points out that the FDA has “taken an industry-friendly approach toward companies using unproven cell cocktails” and that the scant scientific evidence about these treatments, which include injections of platelet-rich plasma, is inconclusive.
For OrthoBuzz readers who want to dive more deeply into the scientific underpinnings (or lack thereof) related to cell therapies for joint problems, please peruse the following JBJS and JBJS Reviews articles, which have been made openly available for a limited period of time:
- Intra-articular Cellular Therapy for Osteoarthritis and Focal Cartilage Defects of the Knee
- Nomenclature Inconsistency and Selective Outcome Reporting Hinder Understanding of Stem Cell Therapy for the Knee
- International Expert Consensus on a Cell Therapy Communication Tool: DOSES
- Stem Cell Therapy for Knee Pain–What Exactly Are We Injecting, and Why?
- A Call for Standardization in Cell Therapy Studies
- A Comprehensive Review of Stem-cell Therapy
The main message running through all these articles is this: Effective clinical assessment and safe, optimized use of cell-based therapies demands greater attention to study methods; standards for cell harvesting, processing, and delivery; and standardized reporting of clinical and structural outcomes.
Assessing Fatty Infiltration in Rotator Cuff Tears: MRI vs Ultrasound
In the setting of rotator cuff injuries, higher degrees of fatty infiltration into cuff muscles are positively correlated with higher repair failure rates and worse clinical outcomes. MRI continues to be the gold standard imaging modality for evaluating fatty infiltration of the rotator cuff, but ultrasound represents another viable modality for that assessment—at considerably lower cost. Such is the conclusion of Tenbrunsel et al. in a recent issue of JBJS Reviews.
The authors reviewed 32 studies that investigated imaging modalities used to assess fatty infiltration and fatty atrophy. They found that grading fatty infiltration using ultrasound correlated well with grading using MRI. However, the authors identified difficulties distinguishing severe from moderate fatty infiltration on ultrasound, but they added that discerning mild from moderate fatty infiltration is more important clinically. Tenbrunsel et al. also mention sonoelastography, which measures tissue elasticity and can also be used to help determine the severity of fatty atrophy of the rotator cuff.
Overall, the trade-off between MRI and ultrasound comes down to higher precision with the former and lower cost with the latter.
For more information about JBJS Reviews, watch this video featuring JBJS Editor-in-Chief Dr. Marc Swiontkowski.
German Knee OA Guidelines Mirror Findings in JBJS Reviews Article
OrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Prof. Joerg Jerosch, in response to a recent article in JBJS Reviews.
I congratulate Vannabouathong et al. for the well-performed and relevant systematic review. In Germany, the Association of Scientific Medical Societies (AWMF) just published a guideline on the medical treatment of knee osteoarthritis (see: https://www.awmf.org/uploads/tx_szleitlinien/033-004l_S2k_Gonarthrose_2018-01_1.pdf), which comes to very similar conclusions as those presented in this systematic review.
The new German guideline suggests a four-stage algorithm starting with topical NSAIDs and escalating to oral NSAIDs (according to individual risks), then followed either by glucosamine, hyaluronic acid (HA), or corticosteroids, and ends finally with opioids. It was very useful that Vannabouathong et al. used the AAOS description for clinical significance, and it was elegant of them to include the effect of intra-articular placebo in their analysis of intra-articular treatments. This review compares treatment-group differences (not within-patient improvements) and considers that the placebo effect in osteoarthritis trials is typically large, particularly in the case of intra-articular injections. Consequently, the measured effect size would underestimate the clinical benefits for patients1, 2. It is valuable that this systematic review calculated the intra-articular placebo versus the oral placebo effect and added the resulting difference of 0.29 standard deviation (SD) units to the respective effect sizes of the intra-articular treatments.
This review concludes that the intra-articular injection of HA has the most concise effect estimate and exceeds the defined threshold of clinical importance of 0.5 SD units. Thus the clinical usefulness of HA is boosted from “possibly clinically important” to “clinically important” according to the AAOS definitions. This review also investigates HA formulations in terms of different molecular weights. It illustrates clearly the effect sizes of high-molecular-weight HA formulations between 1,500 kDa and 6,000 kDa, as well as those above 6,000 kDa.
One point requiring further discussion is that many patients have contraindications to NSAIDs due to comorbidities or comedications. Our new German guideline points out that NSAIDs are contraindicated for elderly patients (>60 years old) and those with existing ulcers, GI bleeding, or infections with H. pylori. Additional contraindicated factors are comedications such as corticosteroids, anticoagulants, or aspirin. In addition, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) reasons that oral NSAIDs have a moderate effect on pain relief, but they are associated with a 3- to 5-fold increase in the risk of upper GI complications, including peptic ulcer perforation, obstruction, and bleeding3.
Another analysis from the Coxib and Traditional NSAID Trialists (CNT) Collaboration shows that 2 to 4 out of 1,000 patients face GI complications after the daily intake of 150 mg of diclofenac. The same applies for 6 to 16 out of 1,000 patients taking 1,000 mg of ibuprofen per day4. An announcement of the Medicines Commission of the German Medical Profession also mentions high relative risks for GI complications associated with NSAIDs. The German guideline recommends intra-articular HA injections especially for individuals at risk for adverse NSAID side effects and for those for whom NSAIDs are not sufficiently effective.
The German guideline also discusses potentially beneficial effects of combining corticosteroids with HA. This should be a topic for a future systematic review.
Prof Joerg Jerosch is a professor of orthopaedic surgery at Johanna-Etienne Hospital in Neuss, Germany.
References
1. Bannuru RR et al., Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis e meta-analysis, Osteoarthritis Cartilage. 2011 Jun;19(6):611-9. doi: 10.1016/j.joca.2010.09.014.
2. Bannuru RR et al., Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis, Ann Intern Med. 2015 Jan 6;162(1):46-54. doi: 10.7326/M14-1231
3. Bruyere O et al. A consensus statement on the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis-From evidence-based medicine to the real-life setting. Semin Arthritis Rheum, 2016. 45(4 Suppl): p. S3-11
4. Bhala N et al., Coxib and traditional NSAID Trialists’ (CNT) Collaboration, Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013; 382(9894): 769-779
JBJS 100: Shoulder Replacement and Odontoid Process Fractures
Under one name or another, The Journal of Bone & Joint Surgery has published quality orthopaedic content spanning three centuries. In 1919, our publication was called the Journal of Orthopaedic Surgery, and the first volume of that journal was Volume 1 of what we know today as JBJS.
Thus, the 24 issues we turn out in 2018 will constitute our 100th volume. To help celebrate this milestone, throughout the year we will be spotlighting 100 of the most influential JBJS articles on OrthoBuzz, making the original content openly accessible for a limited time.
Unlike the scientific rigor of Journal content, the selection of this list was not entirely scientific. About half we picked from “JBJS Classics,” which were chosen previously by current and past JBJS Editors-in-Chief and Deputy Editors. We also selected JBJS articles that have been cited more than 1,000 times in other publications, according to Google Scholar search results. Finally, we considered “activity” on the Web of Science and The Journal’s websites.
We hope you enjoy and benefit from reading these groundbreaking articles from JBJS, as we mark our 100th volume. Here are two more:
Recent Experience in Total Shoulder Replacement
C S Neer, K C Watson, F J Stanton: JBJS, 1982 March; 64 (3): 319
“Recent” in this context refers to more than 30 years ago, but many aspects of this meticulous review of nearly 200 total shoulder replacements, followed for 24 to 99 months, remain instructive. To get a sense of the explosion in research on this topic, compare the 18 references accompanying this study, most citing work by Neer himself, to the 70 references in a 2015 JBJS Reviews article focused on one detail (glenoid bone deficiency) of shoulder replacement.
Fractures of the Odontoid Process of the Axis
L D Anderson and R T D’Alonzo: JBJS, 1974 December; 56 (8): 1663
The basic fracture classification posited in this article has stood the test of time. Since the 1980s, however, surgeons have developed treatments for type-II odontoid fractures that provide direct fixation without the need for fusion and subsequent loss of rotatory motion.
JBJS Reviews Editor’s Choice–Sport-Related SSTIs
I may never go to the gym again!
In the January 2017 issue of JBJS Reviews, Mitchell et al. report on sport-related skin and soft tissue infections (SSTIs) as an ongoing problem across a diverse range of recreational, collegiate, and professional athletes. They note that these infections often occur during training for competitive sports or during the competition and that the majority are bacterial or fungal in origin. The review describes the mechanisms by which SSTIs occur in healthy athletes and the prevalence among players in various sports, including the effect of player position. The authors discuss the mechanisms by which SSTIs are spread and the hygiene measures that are recommended to prevent their spread. They extrapolate these lessons to the general population of so-called weekend warriors or fitness enthusiasts. This is what worries people like me, as studies have shown that these infections easily occur during regular visits to fitness centers and gymnasiums, which are sources of large quantities of bacteria that could cause SSTIs!
Studies have shown that billions of bacteria, fungi, and other microbes inhabit the skin and that the types of organisms vary between individuals and between different sites of the skin. In fact, they may vary in relation to each region of the body. Indeed, factors such as skin characteristics, sebaceous gland concentration, moisture content, temperature, and genetics as well as exogenous environmental factors can influence each so-called community of organisms. The authors hypothesize that sports in which participants have substantial skin-to-skin collisions might disrupt these ecosystems on the skin and allow microbes to be shared among players, noting that contact athletes have been shown to be potential carriers of methicillin-resistant Staphylococcus aureus (MRSA) more than twice as frequently as athletes who participate in noncontact sports. Other mechanisms by which SSTIs occur in healthy athletes include maceration of the skin due to sweating as well as strenuous training. Of particular interest is the observation that extended periods of intense exercise may temporarily depress certain aspects of the immune system, including natural killer cells, neutrophils, lymphocytes, immunoglobulin levels, and interleukin-2 levels and thus facilitate and promote infection and its potential host transfer.
The article goes on to explain how SSTIs are spread, the prevalence of SSTIs among players in various sports, the importance of personal and environmental hygiene, and specific forms of treatment of SSTIs in athletes.
When you do go to the gym or fitness center, just remember to clean off any equipment both before and after use and to change out of your workout clothes and shower as soon as possible after the workout. Be sure to cover benches with a towel, and if you practice yoga, bring your own mat.
I definitely will continue to use the gym but will pay more attention to the issues raised in this review.
Thomas A. Einhorn, MD
Editor, JBJS Reviews
JBJS Reviews Editor’s Choice–Outpatient Joint Replacement?
“Necessity is the mother of invention.” In recent years, the demand for total hip, total knee, and unicompartmental knee arthroplasty has grown substantially. However, with limited resources and health-care budgets, there is a need to reduce hospital costs. To that end, a number of surgeons have begun to perform these procedures on an outpatient basis.
Indeed, as the demand for joint replacements grows, it will be imperative to improve patient safety and satisfaction while minimizing costs and optimizing the use of health-care resources. In order to accomplish this goal, surgical teams, nursing staff, and physiotherapists will need to work together to discharge patients from the hospital as soon as safely possible, including on the same day as the operation. The development of accelerated clinical pathways featuring a multidisciplinary approach and involving a range of health-care professionals will result in extensive preoperative patient education, early mobilization, and intensive physical therapy.
In the December 2016 issue of JBJS Reviews, Pollock et al. report on a systematic review that was performed to determine the safety and feasibility of outpatient total hip, total knee, and unicompartmental knee arthroplasty. The authors hypothesized that outpatient arthroplasty would be safe and feasible and that there would be similar complication rates, similar readmission and revision rates, similar clinical outcomes, and decreased costs in comparison with the findings associated with the inpatient procedure. The investigators demonstrated that, in selective patients, outpatient total hip, total knee, and unicompartmental knee arthroplasty can be performed safely and effectively.
A major caveat of this well-conducted study, however, is that, like any systematic review, its overall quality is based on the quality of the individual studies that make up the analysis. In this case, the studies included those that lacked sufficient internal validity, sample size, methodological consistency, and standardization of protocols and outcomes. Thus, going forward, there is a need for more rigorous and adequately powered randomized trials to definitively establish the safety, efficacy, and feasibility of outpatient hip and knee arthroplasty.
Thomas A. Einhorn, MD
Editor, JBJS Reviews
JBJS Reviews Editor’s Choice–Treating ACL Injuries
One of the observations that I have made during my years in academic medicine is that the more popular a topic appears to be in the literature, the less likely we are to really understand it. After all, if we need to write about it so much, it must mean that there is still much to learn. This certainly seems to be the case with regard to injuries of the anterior cruciate ligament (ACL). ACL injuries are among the most common injuries sustained in the United States. Over 100,000 ACL reconstructions were performed in the United States in 2006, and the annual rate has continued to increase over time. Although some patients have achieved good results after nonoperative treatment, a survey of the American Orthopaedic Society for Sports Medicine showed that the majority of respondents used nonoperative treatment for fewer than 25% of their patients with ACL injuries.
Noyes et al.1 described the so-called “rule of thirds.” According to this rule, one-third of patients with an ACL injury will compensate well with nonoperative treatment (copers), one-third will avoid symptoms of instability by modifying activities (adapters), and one-third will require operative reconstruction (noncopers). Unfortunately, there does not seem to be any way to predict which group an individual patient will fall into. Thus, there is still substantial ambiguity in determining which patients are most likely to benefit from early intervention with ACL reconstruction following injury.
In this month’s issue of JBJS Reviews, Secrist et al. used the literature to perform a comparison of operative and nonoperative treatment of ACL injuries. They noted that only 3 randomized controlled trials have compared operative and nonoperative treatment of ACL injuries and that 2 of those studies involved the use of ACL suturing as opposed to more modern forms of reconstruction. The third study involved only 32 patients. All studies had substantial methodological limitations. The authors concluded that there have been no Level-I studies comparing ACL reconstruction with nonoperative treatment.
In their review article, Secrist et al. attempted to define and evaluate the available data on the natural history of nonoperatively treated ACL injuries and to determine how the functional outcomes and injury risks associated with nonoperative treatment compared with those associated with reconstruction. Moreover, they sought to define prognostic factors and rehabilitation protocols associated with successful operative outcomes. Finally, they compared the outcomes following early versus delayed ACL reconstruction.
However, by the end of the article, one gets the feeling that the authors have “come full circle.” The authors summarize their findings by saying that some patients can cope with a torn ACL and return to preinjury activity levels, including participation in pivoting sports. On the other hand, patients who have an ACL injury along with a concomitant meniscal injury are at increased risk for osteoarthritis, and it is unclear what effect reconstruction of an isolated ACL has on future osteoarthritis risk in ACL-deficient patients who are identified as “copers.”
I suspect that we will continue to see articles on this topic for many years to come. In light of the “rule of thirds” and the additional impact of meniscal injury, the allocation of a particular patient to operative or nonoperative treatment remains unclear.
Thomas A. Einhorn, MD
Editor, JBJS Reviews
Reference
- Noyes FR, Matthews DS, Mooar PA, Grood ES. The symptomatic anterior cruciate-deficient knee. Part II: the results of rehabilitation, activity modification, and counseling on functional disability. J Bone Joint Surg Am. 1983 Feb;65(2):163-74 Medline.
JBJS Reviews Editor’s Choice–Open Fracture Care During War
Injuries to the musculoskeletal system are among the most common wounds of war. Compared with extremity injuries in the civilian population, injuries sustained in combat tend to be due to high-energy explosions and are associated with a greater degree of contamination and a longer timeline for recovery and healing. Importantly, the sequelae of musculoskeletal injuries sustained during combat tend to lead to more long-term disability than those affecting other organ systems.
In this month’s Editor’s Choice article, Rivera et al. review the current literature on combat injuries of the lower extremity and suggest that explosions are the most common mechanism of injury encountered by deployed service members. While exposure to an explosion does not necessarily result in a specific limb injury, the explosion mechanism does contribute to more severe injuries. Moreover, among service members who sustain open fractures of the tibia, foot, and ankle, infection is a common complication and is associated with more severe soft-tissue injury. As a result, surgeons who are deployed in combat settings are now performing more fasciotomies for limbs that are at risk. However, the outcomes and complication rates associated with these procedures are not well established, and the causes of late amputations are not always clear.
As part of a comprehensive review of this topic, Rivera et al. pose 3 important clinical questions that are ideal for translational research investigation. First, they ask, “What is the best way to manage and transport patients who have severe open fractures in order to minimize infection?” Indeed, while negative-pressure wound therapy (NPWT) appears to be a promising wound-care technique, additional study is needed in order to know how to best augment the standard of care for battlefield medicine. Second, “What is the best way to treat fasciotomy wounds and the late sequelae of the compartment syndrome?” In order to answer this question, a broader understanding of compartment syndrome detection and the indications for surgical treatment are needed. Finally, “What is the best way to select limbs for salvage and to optimize the reconstruction of injured tissues?” This question must explore not only the patient’s perspective but also the multitude of causes that lead to late amputation.
Thomas A. Einhorn, MD
Editor, JBJS Reviews
JBJS Reviews Editor’s Choice—Pediatric Infection
Infection, whether acute, chronic, local, or systemic, is something that all surgeons respect and fear. To counter infection, tissue injury activates an acute-phase response mediated by the liver and promotes coagulation, immunity, and tissue regeneration. However, microorganisms are able to survive and disseminate throughout tissues because of virulence factors that they express. These virulence factors help to modulate and hijack the acute-phase response.
In this month’s Editor’s Choice article, An et al. discuss how an understanding of virulence strategies of musculoskeletal pathogens will help to guide clinical diagnosis and decision-making through monitoring of acute-phase markers such as C-reactive protein, the erythrocyte sedimentation rate, and fibrinogen. As pathogenic bacteria possess virulence factors that allow them to invade, persist, and disseminate within the human body, this review focuses on the pathophysiology of musculoskeletal infection and the virulence factors that enable pathogens to thrive within the context of tissue damage.
The authors demonstrate that tissue injury ruptures anatomic compartment boundaries, leading to the contamination of microenvironments that require complex physiological processes for proper temporary repair. Certain organisms, such as Staphylococcus aureus and Streptococcus pyogenes, have evolved mechanisms for evading and hijacking the hemostatic, tissue regenerative, and antimicrobial properties of the acute-phase response. Indeed, a better understanding of the virulence strategies used by pathogenic microorganisms should enhance our ability to treat infections and improve patient outcomes in the future.
Thomas A. Einhorn, MD
Editor, JBJS Reviews
JBJS Reviews Editor’s Choice—Trunnion Wear After THA
Total hip arthroplasty made its debut about 60 years ago. As with most new technologies, it was anticipated that advances and improvements would occur. However, the improvements have been incremental and in some cases have led to problems, particularly with regard to interchangeable parts, modularity, and the materials used for articulating surfaces. Some still believe that total hip arthroplasty was close to being optimized at the time that it was introduced.
Some may view these comments as somewhat provocative, but I would not be surprised if a lot of surgeons agree. The issue of trunnion wear is one example of these problems. One of the main contributing factors is the fact that each implant manufacturer uses tapers with their own specifications, which vary in terms of angle, diameter, straightness, roundness, and surface properties. Therefore, most femoral neck implant tapers are not necessarily compatible with each other. It is important to note that femoral heads should not be used interchangeably between designs as the cone angle may differ. ?If this is done, trunnionosis will be a likely outcome.
In the August 2016 issue of JBJS Reviews, Lanting et al. provide an important and very worthwhile discussion of the risk factors for trunnionosis. Trunnionosis may be enabled by the disruption of the protective oxidative layer on the metal by fretting, potentiating the corrosion of the exposed metal beneath the oxidative layer through an active combination of biochemical and electrochemical processes. Time in vivo consistently has been shown to be a risk factor for trunnionosis. Flexural rigidity of the trunnion has been demonstrated to have an important role in the development of trunnionosis. A flexible trunnion may allow fretting as well as point loading. Edge loading is known to make tribocorrosion more likely to occur. In the presence of any degree of angular mismatch, the effect of trunnionosis may be increased.
The role of design and manufacturing variables in the development of trunnion problems continues to be debated. Surgeon-related factors, especially the greater variability and taper assembly with smaller-incision surgery, also may contribute to this phenomenon. Patients presenting with unexplained pain who have modular neck-body implants should be considered to have an adverse local tissue reaction resulting from corrosion of the neck-stem interface as potential cause of the pain.
In most cases, I suspect that removal of the femoral head, cleaning of the taper, and replacement with a different femoral head (usually a ceramic head with a titanium adapter sleeve) represents adequate treatment based on care recommendations. In contrast, in cases involving adverse local tissue reactions associated with the modular neck designs, removal of the modular stem and neck may be required.
Thomas A. Einhorn, MD
Editor, JBJS Reviews
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