Archive | December 2019

Predicting ‘Fast,’ ‘Slow Starters’ and ‘Late Dippers’ after THA

Based on ample published data and experience, today’s hip surgeons can give patients who are considering total hip arthroplasty (THA) a good general idea of outcomes to expect. But what if orthopaedists could provide more tailored predictions of THA outcome, and thus help patients more realistically manage expectations?

That is essentially what Hesseling et al. set out to do in their database analysis of 6,030 THA patients gleaned from the Dutch Arthroplasty Register; the findings appear in the December 18, 2019 issue of JBJS. Using the patients’ Oxford Hip Scores (OHS) collected up to 1 year postoperatively and a sophisticated statistical technique called latent class growth modeling, the authors categorized outcome trajectories into 3 categories:

  1. Fast Starters (n = 5,290)—steep improvement in OHS during the first 3 postoperative months, after which the OHS leveled out
  2. Late Dippers (n = 463)—more modest improvement in OHS initially, followed by subsequent decline toward the 1-year mark
  3. Slow Starters (n = 277)—virtually no change at the 3-month mark, followed by an improvement in OHS at 1 year postoperatively

Although the authors were unable to tease out factors that clearly distinguished between late dippers and slow starters, they did identify several factors associated with less-than-fast-starter outcomes:

  • Female sex
  • Smoking
  • Age >75 years
  • Obesity
  • Anxiety and depression
  • American Society of Anesthesiologist (ASA) grade III or IV
  • Hybrid fixation (cemented acetabular implant)
  • Direct lateral surgical approach

Emphasizing that all 3 subgroups experienced functional improvement after THA, Hesseling et al. nevertheless provide useful information that can help surgeons more accurately estimate which patients might be at risk of a less favorable recovery.

What’s New in Musculoskeletal Tumor Surgery 2019

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 OrthoBuzz summaries of these “What’s New” articles. This month, author Peter S. Rose, MD selected the most clinically compelling findings from the 40 studies summarized in the December 18, 2019 “What’s New in Musculoskeletal Tumor Surgery.

Staging Primary Bone Tumors
–The American Joint Committee on Cancer (AJCC) issued new staging criteria for primary bone tumors,1 largely in response to clinician reports that pelvic and spinal bone tumors have adverse clinical outcomes compared with extremity tumors. In the AJCC staging system, different criteria are applied to extremity, pelvic (inclusive of the sacrum), and mobile spinal tumors—an important step toward gathering data to better define the prognosis of these tumors.

Bone Metastases
–The skeletal system is the third most common site of metastatic disease, and the most common location of symptomatic skeletal metastases is about the hip. In a risk-adjusted analysis of US Veterans Administration data, Philipp et al. showed that patients with femoral metastases treated prophylactically have a lower risk of death (hazard ratio, 0.75) than similar patients treated after pathological fracture.2

Post-Resection Reconstruction
–Aponte-Tinao et al. investigated the ≥10-year survival of bulk allografts for the femur and tibia, demonstrating 60% graft survival in 166 patients.3 However, proximal tibial osteoarticular grafts fared poorly.

Soft-Tissue Sarcomas
–An analysis of the impact of obesity on soft-tissue sarcoma presentation and management4 arrived at 3 conclusions. Relative to non-obese patients,

  1. Obese patients presented with larger tumors (presumably because of difficulty detecting them).
  2. Obese patients required more complex wound closures.
  3. Obese patients experienced more complications.

–A retrospective analysis of the value of radiotherapy and chemotherapy in treating different subtypes of soft-tissue sarcomas5 revealed that myxoid liposarcomas, vascular sarcomas, and myxofibrosarcomas had the greatest benefit from radiation in terms of local control rates, although there was no difference in overall survival. Chemotherapy resulted in a 5% survival benefit.

References

  1. Kniesl JS, Rosenberg AE, Anderson PM, Antonescu C, Bruland O, Cooper K, Horvai A, Holt G, O’Sullivan B, Patel S, Rose P. Bone. In: Amin M.B., Edge S.B., Greene F.L., Byrd D.R., Brookland R.K., Washington M.K., Gershenwald J.E., Compton C.C., Hess K.R., Sullivan D.C., Jessup J.M., Brierley J.D., Gaspar L.E., Schilsky R.L., Balch C.M.,Winchester D.P., Asare E.A., Madera M., Gress D.M., Vega L.M., editors. AJCC cancer staging manual. 8th ed. Springer; 2018. p 471-86.
  2. Philipp T, Mikula J, Doung Y-C, Gundle K. Is there an association between prophylactic femur stabilization and survival in patients with metastatic bone disease? Clin Orthop Relat Res. 2019 May 17. [Epub ahead of print.]
  3. Aponte-Tinao L, Ayerza M, Albergo J, Farfalli GL. Do massive allograft reconstructions for tumors of the femur and tibia survive 10 or more years after implantation? Clin Orthop Relat Res. 2019 May 17. [Epub ahead of print.]
  4. Montgomery C, Harris J, Siegel E, Suva L, Wilson M, Morell S, Nicholas R. Obesity is associated with larger soft-tissue sarcomas, more surgical complications, and more complex wound closures (obesity leads to larger soft-tissue sarcomas). J Surg Oncol. 2018 Jul;118(1):184-91. Epub 2018 Jun 7.
  5. Callegaro D, Miceli R, Bonvalot S, Ferguson P, Strauss DC, Levy A, Griffin A, Hayes AJ, Stacchiotti S, Le P`echoux C, Smith MJ, Fiore M, Dei Tos AP, Smith HG, Catton C, Casali PG, Wunder JS, Gronchi A. Impact of perioperative chemotherapy and radiotherapy in patients with primary extremity soft tissue sarcoma: retrospective analysis across major histological subtypes and major reference centres. Eur J Cancer. 2018 Dec;105:19-27. Epub 2018 Oct 29.

Vancomycin-Soaked ACL Grafts Cut Already-Low Infection Rates

The word “infection” contains 9 letters, but it’s a four-letter word for orthopaedic surgeons. Postoperative infections are complications that we all deal with, but we try hard to avoid them. Infections after elective sports surgeries can have especially devastating long-term consequences. Thankfully, scientific advances such as  improved sterile techniques and more powerful prophylactic antibiotics have helped us decrease the rates of perioperative infections. But more can always be done in this arena.

Baron et al. discuss one additional infection-fighting approach in the December 18, 2019 issue of JBJS, where they report on findings from a retrospective cohort study that looked at 90-day infection rates after >1,600 anterior cruciate ligament (ACL) reconstructions. Specifically, they investigated whether the rates of infection differed when the ACL grafts were prepared with or without a vancomycin irrigant. The average patient age was 27 years old, and all the surgeries (84.1% of which were primary reconstructions) were performed by 1 of 6 fellowship-trained surgeons. The graft was soaked in vancomycin solution in 798 cases (48.7%), while the remaining 51.3% did not use vancomycin.

Baron et al. found that 11 of the reconstructions were complicated by infection within 90 days, but only 1 of those 11 infections occurred in the vancomycin group (p=0.032). After controlling for various confounding factors, the authors found that increased body mass index and increased operative time were also significantly associated with postoperative infection, while age, sex, smoking, surgeon, and insurance type were not.

These results reveal an 89.4% relative risk reduction in postoperative infections after ACL reconstructions when grafts are bathed in vancomycin solution, although the absolute rate of infection among non-soaked grafts (1.2%) was still quite low. Time and more rigorous study designs will tell us whether this is a big step forward in the evolution of infection prevention, but these results should at least prompt further investigation.

Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media

Total Ankle Arthroplasty: Maybe Not as Finicky as We Thought?

As the orthopaedic community continues to solve complex issues related to joint replacement, it has become apparent that deformity correction and component positioning are keys to long-term success. In terms of hip, knee, and shoulder arthroplasty, we have progressed throughout the last 50 years with improved functional outcomes and component longevity. Elbow arthroplasty development has lagged somewhat because indications for that procedure are much less common.

Meanwhile, total ankle arthroplasty (TAA) experienced a short-lived decade of enthusiasm in the late 1970s and early 1980s before it became apparent that improved component designs and surgical techniques were needed. Progress with TAA stalled until the late 1990s, but TAA has now become more predictable, and several successful designs are available with reasonable revision rates demonstrated during 10-plus years of follow-up. As with all arthroplasties, component alignment in TAA is critical, and we have therefore assumed that significant preoperative frontal plane deformity is a contraindication for this procedure.

However, in the December 18, 2019 issue of The Journal, Lee et al. challenge that assumption with midterm follow-up data on 146 TAAs that suggest patients with frontal plane deformities >20° should not necessarily be disqualified from having this procedure. In this study, prior to surgery, 107 ankles had moderate frontal plane deformity (5° to <15° of varus or valgus) and 41 ankles had severe deformity (>20° to 35° of varus or valgus). The authors found no difference between these groups in terms of functional outcomes, complications, or implant survival at a mean follow-up of 6 years. Lee et al. conclude that frontal malalignment >20° in patients with end-stage ankle osteoarthritis may not be a contraindication to proceeding with TAA. However, the authors emphasize that concomitant realignment procedures at the time of index arthroplasty (including ligament releases and corrective osteotomies) were much more common in the severe group.

These findings need confirmation from other groups and with longer-term follow-up so that data from lower-volume surgeons can be analyzed and later complications can be investigated. Still, it just may be that ankle arthroplasty is not as finicky as we have been thinking.

Marc Swiontkowski, MD
JBJS Editor-in-Chief

Shedding Low-Level Laser Light on Knee OA

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.

Low-level laser therapy (LLLT) has been used in multiple countries to treat the pain and function deficits associated with knee osteoarthritis (OA). The wavelength typically used is in the near-infrared region. However, this therapy is not recommended by most clinical guidelines, including those of the Osteoarthritis Research Society International. The hesitancy to recommend LLLT is due largely to conflicting published findings and unresolved dose-related issues such as wavelength, intensity, and frequency of treatment. For treating knee OA, the World Association for Laser Therapy (WALT) recommends applying four times the laser dose with continuous rather than pulsed irradiation.

To try to resolve conflicting evidence, Stausholm et al. conducted a systematic review and meta-analysis of randomized, placebo-controlled trials of LLLT, distilling 22 trials from 2,735 initially identified articles.1 Pain, as measured by a 0 to 100 mm visual analog scale (VAS), was significantly reduced by LLLT compared with placebo at the end of therapy (14.23 mm VAS; 95% CI 7.31 to 21.14) and during follow-ups 1 to 12 weeks later (15.92 mm VAS; 95% CI 6.47 to 25.37). Subgroup analysis revealed that pain was significantly reduced by the recommended LLLT doses compared with placebo at the end of therapy (18.71 mm VAS; 95% CI 9.42 to 27.99) and during follow-ups 2 to 12 weeks after the end of therapy (23.23 mm VAS; 95% CI 10.60 to 35.86).

Pain reduction from the recommended doses peaked during follow-ups 2 to 4 weeks after the end of therapy. Disability was also significantly reduced by LLLT, and no adverse events were reported in any of the studies. Notably, in light of JBJS Editor-in-Chief Marc Swiontkowski’s recent comments about the quality of meta-analyses, this meta-analysis was reported in accordance with PRISMA guidelines and all included trials were evaluated for risk of bias.

What remains unclear is how far past the skin the varied wavelengths and intensities (usually 1 to 8 Joules) of laser energy penetrate. Likewise, tissue heating has not been measured or analyzed. Still, at present, it appears that LLLT used with WALT guidelines is a safe and potentially effective treatment for the pain and dysfunction of knee OA.

Reference

  1. Stausholm MB, Naterstad IF Msc, Joensen J, Lopes-Martins RÁB, Sæbø H Msc, Lund H, Fersum KV, Bjordal JM. Efficacy of low-level laser therapy on pain and disability in knee osteoarthritis: systematic review and meta-analysis of randomised placebo-controlled trials. BMJ Open. 2019 Oct 28;9(10):e031142. doi: 10.1136/bmjopen-2019-031142. PMID: 31662383

What’s New in Musculoskeletal Basic Science 2019

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 summaries. This month, co-author Philipp B. Leucht, MD selected the most clinically compelling findings from the 40 studies summarized in the December 4, 2019 “What’s New in Musculoskeletal Basic Science.

Muscle Regeneration
–Recent findings about the cellular players in muscle regeneration may allow further development of clinical treatment options for patients with muscle sprains, tears, and loss. Toward that end, Wosczyna et al. established the crucial role of fibroadipogenic progenitors (FAPs, also called mesenchymal stromal cells) in muscle repair and maintenance.1 Using a mouse model, the researchers showed that FAPs are necessary for muscle regeneration by supporting muscle stem cells.

Bone-Brain Crosstalk
–The bone-derived hormone osteocalcin supports development of the musculoskeletal system and the brain. Osteocalcin can regulate anxiety and cognition in adult mice, and Obri et al. postulated that declining levels of osteocalcin may be responsible for the cognitive decline seen in aging.2 This finding may spur investigations into exogenous treatment with osteocalcin to restore brain function.

Tendon Regeneration
–Tendon cells express the transcription factor Scleraxis, which has facilitated the identification of the tendon stem progenitor cell (TSPC). Best and Loiselle identified a Scleraxis-positive cell population in the bridging scar tissue after tendon injury.3 These findings suggest that TSPCs are present in the adult tendon and contribute to the healing response; however, their small number does not result in successful tendon regeneration, but rather in scar formation with interspersed tendon tissue.

–Abraham et al. identified the upregulation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and its downstream targets in tendinopathy-affected human rotator cuff tendons.4 Using a transgenic mouse model in which IKKß (inhibitor of nuclear factor kappa-B kinase subunit beta), a key regulator of inflammation, was overexpressed, they demonstrated the development of tendinopathy in mouse rotator cuff tendons. The deletion of IKKß had a protective effect from chronic overuse.

Bone Regeneration
–Successful bone healing after fracture is highly dependent on the presence and activation of skeletal stem cells. Chan et al. precisely defined the human skeletal stem cell (hSSC), demonstrated the hSSC’s role in human fracture repair, and provided evidence that these cells generate a bone marrow-supportive niche.5 These cells also give rise to bone, cartilage, and stromal progenitor cells.

References

  1. Wosczyna MN, Konishi CT, Perez Carbajal EE, Wang TT, Walsh RA, Gan Q, Wagner MW, Rando TA. Mesenchymal stromal cells are required for regeneration and homeostatic maintenance of skeletal muscle. Cell Rep.2019 May 14;27(7):2029-2035.e5.
  2. Obri A, Khrimian L, Karsenty G, Oury F. Osteocalcin in the brain: from embryonic development to age-related decline in cognition. Nat Rev Endocrinol.2018 Mar;14(3):174-82. Epub 2018 Jan 29.
  3. Best KT, Loiselle AE. Scleraxis lineage cells contribute to organized bridging tissue during tendon healing and identify a subpopulation of resident tendon cells. FASEB J.2019 Jul;33(7):8578-87. Epub 2019 Apr 5.
  4. Abraham AC, Shah SA, Golman M, Song L, Li X, Kurtaliaj I, Akbar M, Millar NL, Abu-Amer Y, Galatz LM, Thomopoulos S. Targeting the NF-κB signaling pathway in chronic tendon disease. Sci Transl Med.2019 Feb 27;11(481):eaav4319.
  5. Chan CKF, Gulati GS, Sinha R, Tompkins JV, Lopez M, Carter AC, Ransom RC, Reinisch A, Wearda T, Murphy M, Brewer RE, Koepke LS, Marecic O, Manjunath A, Seo EY, Leavitt T, Lu WJ, Nguyen A, Conley SD, Salhotra A, Ambrosi TH, Borrelli MR, Siebel T, Chan K, Schallmoser K, Seita J, Sahoo D, Goodnough H, Bishop J, Gardner M, Majeti R, Wan DC, Goodman S, Weissman IL, Chang HY, Longaker MT. Identification of the human skeletal stem cell. 2018; Sep 20;175(1):43-56.e21.

3 Reference Axes Help Ensure Rotational Alignment During TKA

Rotational malalignment of the femoral component during total knee arthroplasty (TKA) is associated with poor outcomes, but how best to assess femoral component rotation intraoperatively remains an unanswered question for arthroplasty surgeons. Now, in the largest study of its kind, Jang et al. conclude in the December 4, 2019 issue of JBJS that combining 3 reference axes is the optimal strategy for ensuring accurate femoral component positioning, sex/ethnic generalizability, and intraoperative efficiency.

The authors compared 5 reference axes commonly used for intraoperative assessment of femoral component rotation by mapping them to >2,100 entire-femur CT scans from patients with nonarthritic knees. Using the surgical transepicondylar axis (sTEA) as the gold-standard reference, Jang et al. found that no single other axis was both highly accurate and relatively immune to ethnic and sex variability. Based on their findings, they instead recommend using a combination of 3 axes—posterior condylar axis externally rotated 3° (PCA + 3° ER), the Whiteside or sulcus line, and the anatomical transepicondylar axis (aTEA)—to ensure rotational alignment.

The authors also suggest a straightforward intraoperative process for using these 3 axes:

  1. Start with the PCA + 3° ER, which most accurately approximates the gold-standard sTEA.
  2. Then use the Whiteside or sulcus line, neither of which is significantly affected by sex or ethnicity.
  3. Finally, palpate for the aTEA to narrow the margin of error.

Citing a limitation to this CT-based study of nonarthritic knees, the authors note that “we could not account for the effects of cartilage wear or other changes caused by degenerative arthritis.”

RCT: Single IV Dose of TXA Is Safe, Effective for TKA

Along the spectrum of early and late adopters in medicine, most orthopaedic surgeons fall in the middle. They wait for science to prove the efficacy and safety of an innovation, carefully review the published studies regarding that innovation, and adopt it if it will improve their patients’ outcomes.

In the December 4, 2019 issue of JBJS, Jules-Elysee et al. compare tranexamic acid (TXA) administered intravenously (IV) versus topically in a double-blinded, randomized controlled trial (RCT) of patients undergoing primary total knee arthroplasty (TKA).  Level-I evidence is rare in the orthopaedic literature, so when a well-performed RCT comes out, we should closely evaluate its findings.

A potent antifibrinolytic, TXA has been shown in multiple studies to decrease blood loss associated with major orthopaedic procedures. However, there are persistent (but not necessarily evidence-based) concerns about its potential to cause thrombogenic complications,  and the safest and most effective route of TXA administration remains an open question.

In this study, the IV group received TXA once before tourniquet inflation and again 3 hours later, along with a topical placebo given 5 minutes before tourniquet release.  The topical group received an IV placebo at the same time intervals as the IV group, along with TXA delivered topically in the wound prior to tourniquet release. The authors found lower systemic levels of plasmin-anti-plasmin (PAP, a measure of fibrinolysis) in both groups 1 hour after tourniquet release, but PAP levels remained significantly lower in the IV group (indicating higher antifibrinolytic activity) 4 hours after tourniquet release, which was likely related to the second IV dose of TXA.

The authors also found no between-group difference in systemic or wound levels of prothrombin fragment 1.2 (PF1.2, a marker of thrombin generation), indicating there was no increase in thrombogenicity in the IV group.  Interestingly, Jules-Elysee also found that the IV group had significantly higher hemoglobin and hematocrit levels 1 and 2 days after surgery, and those patients had a significantly shorter hospital stay.

Finding no major between-group differences in the mechanism of action, coagulation, or fibrinolytic profile, the authors concluded that a single IV dose of TXA may be the most simple protocol for hospitals to adopt if they are still concerned about TXA safety. Perhaps these Level-I findings will help some of the late adopters get over their fears about the safety of IV TXA.

Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media

Meta-Analysis Quality Improving, But Issues Remain

Hip and knee arthroplasty are common procedures worldwide and are increasing annually as demographics change and the technical aspects of these surgeries become more accessible to a broader swath of surgeons. The sheer number of these procedures makes them an appropriate focus for randomized controlled trials (RCTs). The aggregation of RCT data into more powerful statistical frameworks is the job of a meta-analysis.

Not surprisingly, we have seen an increasing number of meta-analyses related to hip and knee replacement published across all major orthopaedic journals during the last two decades. Authors have two common motivations for conducting meta-analyses. The first, to summarize data from carefully conducted RCTs into clinically relevant and important recommendations, is hopefully the most common motivation—and certainly the most justifiable. The second, to merely use previously published data as an analytic exercise to advance one’s academic career without investing the time and effort to do prospective research, is not justifiable, in my estimation.

In the December 4, 2019 issue of The Journal, Park et al. conduct quality and usefulness assessments of 114 published meta-analyses about hip and knee arthroplasty that appeared in 3 major orthopaedic journals (one of which was JBJS) from 2000 to 2017. They document a nearly 4-fold increase in the number of meta-analyses published on these topics when comparing 2000 to 2009 with 2010 to 2017. Based on Oxman-Guyatt Index scores of overall study quality, only 12 of the 114 studies were assessed as high quality, 87 as moderate quality, and 15 as low quality.

Here are some additional findings:

  • The majority of these meta-analyses were not performed in accordance with established PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.
  • Only 39% of these articles showed the risk of bias.
  • Many of these meta-analyses covered redundant topics within the same year or within a few years of each other.
  • A review by expert attending surgeons of the 24 studies determined to be high quality per PRISMA found that 71% were either clinically unimportant or inconclusive.

It is a positive step to highlight for our readers the important quality issues surrounding meta-analyses, and I agree with James Stoney, who commented on these findings: “The onus is on surgeons to carefully scrutinize meta-analyses…and come to individual conclusions about the quality of the research rather than accept the conclusions at face value.”

But I am discouraged to see the number of problematic meta-analyses that have appeared in our literature, and I suspect most of these quality problems arise from the second, unjustifiable motivation noted above. We need to do better as a research community, as peer reviewers, and as journal editors to improve the quality of published meta-analyses so that we can favorably impact patient care and advance the clinical practice of hip and knee arthroplasty.

Marc Swiontkowski, MD
JBJS Editor-in-Chief