FDA OKs Synthetic Implant for Repairing ACL Tears
OrthoBuzz has been following the development of the Bridge-Enhanced ACL Repair (BEAR) implant—a synthetic alternative to graft-based anterior cruciate ligament reconstruction—since 2015 (see previous OrthoBuzz posts). On December 16, 2020 the FDA granted authorization to Miach Orthopaedics, Inc. to market the implant.
The BEAR implant is made from bovine collagen. After securing it with sutures to the torn ends of a completely ruptured ACL, the surgeon injects the patient’s own blood into the implant, which forms a clot that enhances ligament healing. Within 8 weeks, the implant is resorbed and replaced by the body’s own tissue.
The FDA’s authorization was based on results from a 100-patient randomized clinical trial, in which 65 patients received the BEAR implant and 35 underwent conventional autograft reconstruction. After 2 years, patient-reported outcomes in both groups were similar for pain, knee function, and sports activity, and arthrometry showed nearly identical joint-laxity outcomes. It remains to be seen how durable the BEAR implant will be over time and how much arthritis will develop in BEAR-treated knees 15 or 20 years from now.
The FDA’s marketing authorization for the BEAR implant was granted under the agency’s de novo device review pathway. That means that subsequent similar devices can be reviewed through the FDA’s 510(k) process, which requires a demonstration of “substantial equivalence” to the predicate device.
Elite Reviewer Spotlight: Steven Olson
JBJS is pleased once again to highlight our Elite Reviewers. The Elite Reviewers Program recognizes our best reviewers for their outstanding efforts. All JBJS reviewers help us maintain the highest standards for quality orthopaedic publishing.
Name:
Steven A. Olson, MD
Affiliation:
Duke University School of Medicine
Years in practice: 27
How did you begin reviewing for other journals and for JBJS in particular?
I was sent a request for a review by Bob Bucholz years ago.
What is your top piece of advice for those reviewers who aspire to reach Elite status?
Be thoughtful, and try to help the authors find ways to make the manuscript better for the reader.
Aside from orthopaedic manuscripts, what have you been reading lately?
Founding Brothers, How to be an Anti-Racist.
Learn more about the JBJS Elite Reviewers program.
Knee OA: Does It Start with Stiff Menisci or Soft Cartilage?
This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.
As an orthopaedic surgeon, I often noticed the rigidity of the meniscus as I excised it during a total knee replacement. Focused on the job at hand, however, I never closely considered the involvement of menisci in degenerative joint disease. But German researchers recently hypothesized that early biomechanical changes in meniscal tissue occur before articular cartilage changes in knee osteoarthritis.1
To test their hypothesis, they dissected 12 cadaver knees with Kellgren-Lawrence (KL) scores between 1 and 2 and 12 knees with KL scores between 3 and 4. The menisci were carefully embedded in a cast of polymethylmethacrylate using bony attachments to hold the specimens for Einst testing at the anterior horn, pars intermedia, and posterior horn. (Instantaneous modulus of elasticity [Einst] is the measure of the initial response of a viscoelastic material to an initial load before long-term deformity occurs.) The exposed tibial surface was then cut 10 mm below the joint for Einst testing at the same zones, and the researchers also measured the articular cartilage-to-cartilage contact area.
Mann-Whitney U-testing revealed higher meniscal Einst values with increasing degeneration for both lateral and medial menisci, while the underlying tibial articular cartilage showed a decrease in Einst in the medial compartment. These findings suggest that knee joint degeneration might very well begin with a stiffening of the menisci, followed by articular cartilage softening.
The wide variation in Einst values uncovered in this study leaves open the possibility there is more than one pathway by which the biochemical response to meniscal cytokine expression would lead to subsequent articular cartilage breakdown. Nevertheless, the authors suggest that their findings might prompt the treatment and diagnostic paradigms of knee osteoarthritis to change, “focusing on the degeneration detection of the menisci instead of the articular cartilage.”
Reference
- Seitz AM, Osthaus F, Ignatius A, Dürselen L. Degeneration alters first the biomechanical properties of human menisci before affecting the tibial cartilage. ORS 2020 Annual Meeting Paper No.0687
A Deeper Dive into Diabetes and Total Joint Replacement
There are many more “types” of diabetes than the pathophysiologic designations of Type 1 and Type 2. In the December 16, 2020 issue of The Journal of Bone & Joint Surgery, Na et al. delineate 4 different diabetes categories and determine their impact on 90-day complications and readmission rates after elective total joint arthroplasty (TJA) among Medicare patients. One premise for this investigation was that, although diabetes is a known risk factor for arthroplasty complications, alternative payment models such as the federally run Comprehensive Care for Joint Replacement (CJR) program adjust their payments only in diabetes cases where the comorbidity is coded as severe.
The authors stratified diabetes into 4 groups as follows:
- No diabetes
- Controlled-uncomplicated diabetes
- Controlled-complicated diabetes
- Uncontrolled diabetes
Among the >500,000 total knee arthroplasties (TKAs) and total hip arthroplasties (THAs) analyzed, the authors found the following when comparing data from the 3 diabetes groups with the no-diabetes group:
- The odds of TKA complications were significantly higher for those with uncontrolled diabetes (odds ratio [OR] = 1.29).
- The odds of THA complications were significantly higher for those with controlled-complicated diabetes (OR = 1.45).
- The odds of readmission were significantly higher in all diabetes groups for both TKA (ORs = 1.21 to 1.48) and THA (ORs = 1.20 to 1.70).
The authors come to 3 basic conclusions based on these findings:
- The odds of hospital readmission and complications following an elective TKA or THA are increased for Medicare beneficiaries who have diabetes.
- It would be reasonable to defer arthroplasty surgery for those with uncontrolled diabetes to allow them to achieve glycemic control.
- The Centers for Medicare & Medicaid Services should include less-severe diabetes and associated systemic complications in alternative-payment model adjustments.
Click here for an “Author Insight” video about this study from co-author Annalisa Na, PhD, DPT.
A Thank You to JBJS Elite Reviewers
We would like to express our sincerest gratitude for all of our Elite Reviewers. These are a select group of individuals who go above and beyond the Reviewer duties and provide consistent, quality reviews for all submissions. We would not be able to uphold our high standards for peer-review without their contributions.
- Julie Agel
- Robert Arciero
- Jan Bartoníček
- Ross A. Benthien
- John G. Birch
- R. Dale Blasier
- Thomas J. Blumenfeld
- Martin Boublik
- Keith Bridwell
- Chew Ee Ming Darryl
- Charles N. Cornell
- Roger Cornwall
- Thomas A. DeCoster
- Douglas R. Dirschl
- Lori Ann Dolan
- Lawrence D. Dorr
- Shivi Duggal
- Paul, J. Duwelius
- Nicholas J. Giori
- H. Kerr Graham
- A. Seth Greenwald
- Allan E. Gross
- Christopher D. Harner
- Iftach Hetsroni
- Nitin Jain
- David S. Jevsevar
- Charles E. Johnston
- Grant Lloyd Jones
- Michael P. Kelly
- Andrew P. Kurmis
- Nicholas Kusnezov
- William D. Lack
- Simon M. Lambert
- Mark Chong Lee
- Paul E. Levin
- Jonathan C. Levy
- Morio Matsumoto
- Terence E. McIff
- Michael D. McKee
- Harry A. McKellop
- Dana C. Mears
- Saeed Miramini
- Fred R. Nelson
- Peter O. Newton
- Kanu Okike
- Steven A. Olson
- Terrance Peabody
- Stephen Pinney
- Kodali Siva Rama Krishna Prasad
- Per-Henrik Randsborg
- David Ring
- Peter S. Rose
- Robert C. Schenck, Jr.
- Herbert S. Schwartz
- Edward M. Schwarz
- William F. Scully
- Howard Seeherman
- David A. Spiegel
- Michael A. Stone
- James B. Talmage
- Lauren M. Tatman
- James E. Tibone
- Daniel G. Tobert
- Thomas Parker Vail
- Andre J. van Wijnen
- Arvind G. von Keudell
- Brian C. Werner
- Carol A. Wise
- David A. Wong
- Jacques T. YaDeau
- Adolph J. Yates, Jr.
Read more about our Elite Reviewers Program here.
What’s New in Musculoskeletal Tumor Surgery 2020
Every month, JBJS publishes 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 such OrthoBuzz specialty-update summaries.
This month, author Peter S. Rose, MD summarized the 5 most compelling findings from the 40 studies highlighted in the December 16, 2020 “What’s New in Musculoskeletal Tumor Surgery.”
Primary Bone Tumors
–A retrospective analysis of data from the Euro-EWING99 trial1 is probably the most thorough examination to date of local tumor-control options in Ewing’s sarcoma of the pelvis–a difficult and controversial condition. The authors conclude with a recommendation for aggressive surgery and radiation in many patients, which goes beyond what most North American centers provide.
Metastatic Tumors
–Anderson et al. validate a fracture-risk calculating app2 that provides immediate clinical guidance on the risk of fracture and the role for surgery in patients with skeletal metastases. It is an early example of applying digital technology to provide real-time, individualized clinical guidance.
Phantom Limb Pain
–Alexander et al. provide an excellent early report of a new surgical technique3 (targeted muscle reinnervation) and a focused rehabilitation protocol to decrease phantom limb pain and maximize function after oncologic amputations.
Soft-Tissue Sarcomas
–After analyzing >1,600 patients treated for a soft-tissue sarcoma, Bedi et al. put forth a nomogram4 to predict postoperative wound complications, the single most frequent surgical complication in this population. The finding that BMI, tumor location, and timing of radiation are associated with the risk of wound complications is clinically relevant to all surgeons who treat these patients.
Carcinogenesis from Radiation Exposure
–This thought-provoking study predicted a lifetime fatal cancer risk of 3.5% from medical imaging studies used in the care of polytrauma patients. While the study focused on trauma patients rather than oncology patients, the striking results may have implications for how we use CT imaging to follow tumor patients as well.
References
- Andreou D, Ranft A, Gosheger G, Timmermann B, Ladenstein R, Hartmann W, Bauer S, Baumhoer D, van den Berg H, Dijkstra PDS, Dürr HR, Gelderblom H, Hardes J, Hjorth L, Kreyer J, Kruseova J, Leithner A, Scobioala S, Streitbürger A, Tunn PU, Wardelmann E, Windhager R, Jürgens H, Dirksen U; GPOH-Euro-EWING99 Consortium. Which factors are associated with local control and survival of patients with localized pelvic Ewing’s sarcoma? A retrospective analysis of data from the Euro-EWING99 trial. Clin Orthop Relat Res.2020 Feb;478(2):290-302.
- Anderson AB, Wedin R, Fabbri N, Boland P, Healey J, Forsberg JA. External validation of PATHFx version 3.0 in patients treated surgically and nonsurgically for symptomatic skeletal metastases. Clin Orthop Relat Res.2020 Apr;478(4):808-18.
- Alexander JH, Jordan SW, West JM, Compston A, Fugitt J, Bowen JB, Dumanian GA, Pollock R, Mayerson JL, Scharschmidt TJ, Valerio IL. Targeted muscle reinnervation in oncologic amputees: early experience of a novel institutional protocol. J Surg Oncol.2019 Sep;120(3):348-58. Epub 2019 Jun 13.
- Bedi M, Ethun CG, Charlson J, Tran TB, Poultsides G, Grignol V, Howard JH, Tseng J, Roggin KK, Chouliaras K, Votanopoulos K, Cullinan D, Fields RC, Cardona K, King DM. Is a nomogram able to predict postoperative wound complications in localized soft-tissue sarcomas of the extremity? Clin Orthop Relat Res.2020 Mar;478(3):550-9.
Elite Reviewer Spotlight: Adolph Yates
JBJS is pleased once again to highlight our Elite Reviewers. The Elite Reviewers Program recognizes our best reviewers for their outstanding efforts. All JBJS reviewers help us maintain the highest standards for quality orthopaedic publishing.
Name:
Adolph “Chick” Yates, Jr., MD
Affiliation:
University of Pittsburgh
Pittsburgh, PA
Years in practice: 31
How did you begin reviewing for other journals and for JBJS in particular?
For some I volunteered and for others I got “volunteered”.
What is your top piece of advice for those reviewers who aspire to reach Elite status?
- Take on every request
- Strive to make the review helpful to the author(s).
- Look for ways to reward hard work that needs help getting expressed.
Aside from orthopaedic manuscripts, what have you been reading lately?
Given the election year, the offerings from Real Clear Politics as well as multiple papers on COVID-19 from PubMed searches.
Learn more about the JBJS Elite Reviewers program.
Patient Misperception of Musculoskeletal Disease Onset
Often when I ask patients about the reason for their visit, I inquire about specific events. For example, “What were you doing when you hurt your knee?” For acute injuries, they can usually describe the exact moment they tore their ACL or dislocated their shoulder. In an adolescent sports clinic, where I spend much of my time, this acute scenario is the norm, but what about patient conversations regarding gradual-onset disease processes such as carpal tunnel syndrome (CTS) or osteoarthritis? These pathologies develop over many years, but patients with such conditions may fixate on when their disease became symptomatic–and may therefore mistakenly attribute a chronic condition to an acute injury.
Lemmers et al. investigate this complex body-mind concept in the December 16, 2020 issue of The Journal. The authors sought to analyze factors associated with the misperception of disease onset due to the recent experience of symptoms in 121 adult patients with CTS, cubital tunnel syndrome, upper-extremity osteoarthritis, or rotator cuff tendinosis. The patients filled out questionnaires for depression, anxiety, pain catastrophizing, self-efficacy, and upper-extremity physical function, in addition to supplying basic demographic information.
Based on the responses, most patients understood that their problem was not new but was instead “age-appropriate.” However, 18% of patients perceived the sudden onset of symptoms as a “new” disease, and 24% felt the problem was related to at least 1 injury or event. After multivariable analysis, Lemmers et al. found that Hispanic ethnicity and publicly funded or no insurance were independently associated with the perception that an event/injury caused the problem. The authors candidly admit that this area needs much more research, but they surmise that this latter finding could be related to lower health literacy.
This work highlights that we need to make sure our patients understand exactly what is happening with their musculoskeletal system. Because misperception of a disease’s cause and onset could affect patient decision-making, it is incumbent upon us as surgeons to be vigilant for possible misconceptions during our shared decision-making discussions with patients. As Lemmers et al. conclude, “Patients who do not understand what is happening to their body might choose different health strategies than they would if their understanding were accurate.”
Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media
Surgical Costs: Just the Half of It
Total-cost breakdown for ankle-fracture patients treated nonoperatively.
The Journal is receiving an increasing number of manuscripts related to value assessments and cost-effectiveness analyses of treatments for orthopaedic pathologies. This line of investigation is crucial to helping the larger healthcare system lower costs while improving patient outcomes. One aspect of determining the total cost of a musculoskeletal intervention is the impact of so-called indirect costs. Components of indirect costs include lost patient wages from not working, higher transportation costs, and extra dollars spent by the individual or family to manage household chores and self-care.
In the December 16, 2020 issue of The Journal, Noback et al. examine the total, direct, and indirect costs of care among 60 patients with a lateral malleolar fracture that was treated either nonsurgically or surgically. They found that in many cases, indirect costs exceeded the direct cost of delivering medical/surgical care. Not surprisingly, this was especially true in nonoperatively treated patients, where three-quarters of the total cost were indirect costs (see Figure).
I believe that our community needs to more widely appreciate and study the impact of patients’ lost wage-earning opportunities and out-of-pocket expenditures. Every treatment recommendation we make in clinical practice involves these financial implications for our patients. Noback et al. go so far as to claim that “any cost-effectiveness analysis… must assess indirect costs or it risks drastically mischaracterizing a treatment’s value.”
We therefore should continue pushing our treatment and rehabilitation strategies to more aggressively limit time lost to full weight-bearing or use of the upper limb. Also, orthopaedic research should be directed toward strategies that limit the impact of indirect costs and family burdens as we seek to continuously improve care for our patients.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
What’s New in Musculoskeletal Basic Science 2020
Every month, JBJS publishes 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 such OrthoBuzz specialty-update summaries.
This month, co-author Philipp Leucht, MD selected the most compelling findings from the 15 studies summarized in the December 2, 2020 “What’s New in Musculoskeletal Basic Science.”
Spine: Annulus Fibrosus Findings
The relatively high prevalence of repeat discectomies has caused researchers to focus on characteristics of the annulus fibrosus, the healing of which often remains incomplete after disc herniation.
–Knowing that the neonatal annulus fibrosus shows regenerative capacity, researchers recently identified Scleraxis-lineage cells as the main contributors to those regenerative properties.1 They discovered that the neonatal cellular programming that results in complete functional restoration of the annulus fibrosus is completely absent in the adult annulus fibrosus after injury. Knowledge of this regenerative mechanism could help scientists develop new treatments for annulus fibrosus regeneration in adults.
–Related research demonstrated that the residual strain of the healthy nucleus pulposus generates pre-strain in the outer annulus fibrosus, and that the loss of residual strain, as seen in disc herniation, results in short-term apoptosis and the emergence of a fibrotic cell phenotype in the annulus fibrosus.2 Blocking cell contractility pathways may therefore offer a viable target to prevent post-injury fibrosis.
Spine: Somitogenesis
–The somitogenesis process in vertebrate development is believed to be controlled by an oscillating genetic “clock.” Researchers developed an in vitro modeling system to recapitulate the human segmentation clock,3 determining that the clock causes a new somite to be formed every 5 hours. This model allowed investigators to assess the function of mutations involved in segmentation defects such as congenital spondylocostal dysostosis. This easily manipulated model could provide the framework for discoveries of the gene oscillations and molecular underpinnings in both normal and abnormal vertebral development.
Osteoarthritis
–Transforming growth factor beta (TGF-β) signaling has been revealing in studying osteoarthritis. Researchers found that mice lacking in Prx1 osteochondral progenitors during development showed joint developmental defects.4 They further found that both postnatal ablation of Tgfbr2 in osteochondral progenitors and pharmacological inhibition of TGF-β receptor 2 led to an osteoarthritis phenotype with accompanied upregulation of the receptor antagonist IL-36α. They then discovered that an IL-36Ra intra-articular injection attenuates osteoarthritis progression in both Tgfbr2-deletion and posttraumatic arthritis models, confirming the IL-36 family as a viable target in fighting osteoarthritis.
Bone Regeneration
–Skeletal stem and progenitor cells migrate to sites of damage after an injury to participate in the repair process. Researchers recently discovered that the quiescent CXCL12-expressing perisinusoidal bone marrow stromal cells also participate in the repair process5 by converting into a skeletal stem-cell-like state after injury. These CCXL12-positive cells are highly malleable and long-living and thus represent an ideal source for bone tissue regeneration.
References
- Torre OM, Mroz V, Benitez ARM, Huang AH, Iatridis JC. Neonatal annulus fibrosus regeneration occurs via recruitment and proliferation of Scleraxis-lineage cells. NPJ Regen Med.2019 Dec 20;4:23.
- Bonnevie ED, Gullbrand SE, Ashinsky BG, Tsinman TK, Elliott DM, Chao PG, Smith HE, Mauck RL. Aberrant mechanosensing in injured intervertebral discs as a result of boundary-constraint disruption and residual-strain loss. Nat Biomed Eng.2019 Dec;3(12):998-1008. Epub 2019 Oct 14.
- Matsuda M, Yamanaka Y, Uemura M, Osawa M, Saito MK, Nagahashi A, Nishio M, Guo L, Ikegawa S, Sakurai S, Kihara S, Maurissen TL, Nakamura M, Matsumoto T, Yoshitomi H, Ikeya M, Kawakami N, Yamamoto T, Woltjen K, Ebisuya M, Toguchida J, Alev C. Recapitulating the human segmentation clock with pluripotent stem cells. 2020 Apr;580(7801):124-9. Epub 2020 Apr 1.
- Li T, Chubinskaya S, Esposito A, Jin X, Tagliafierro L, Loeser R, Hakimiyan AA, Longobardi L, Ozkan H, Spagnoli A. TGF-β type 2 receptor-mediated modulation of the IL-36 family can be therapeutically targeted in osteoarthritis. Sci Transl Med.2019 May 8;11(491):eaan2585.
- Matsushita Y, Nagata M, Kozloff KM, Welch JD, Mizuhashi K, Tokavanich N, Hallett SA, Link DC, Nagasawa T, Ono W, Ono N. A Wnt-mediated transformation of the bone marrow stromal cell identity orchestrates skeletal regeneration. Nat Commun.2020 Jan 16;11(1):332.
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