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Rapid Alpha Defensin Test Helpful for Diagnosing PJI

Synovasure for OBuzzQuick and accurate: that’s what orthopaedic surgeons want in diagnostic tools to help them determine whether patients presenting with pain after total joint arthroplasty have an infection. A prospective Level I study by Gehrke et al. in the January 3, 2018 issue of The Journal of Bone & Joint Surgery determined that a new lateral flow version of the Synovasure Alpha Defensin Test meets those requirements.

Alpha defensin is a protein secreted by neutrophils in response to bacterial infection, prior to the development of specific immune responses. Earlier research established alpha defensin in synovial aspirates to be an excellent biomarker for periprosthetic joint infection (PJI). The original ELISA-based alpha defensin test is usually sent out for 24-hour processing, limiting its intraoperative utility. However, the lateral flow version of the test (akin to an over-the-counter pregnancy test) was approved for use in Europe—and its results are available in 10 to 15 minutes.

Gehrke et al. compared the rapid test’s results to the diagnostic criteria promulgated by the Musculoskeletal Infection Society (MSIS). According to MSIS criteria, there were 76 joints with PJI among 191 study subjects on whom 195 joint aspirations were performed. Using that as the benchmark for diagnosis, the authors analyzed results from the rapid alpha defensin tests and found the following performance:

  • 92.1% sensitivity
  • 100% specificity
  • 100% positive predictive value
  • 95.2% negative predictive value
  • 96.9% overall accuracy

Although the rapid test does not provide information about the identity of specific pathogens, the authors conclude that it “enables surgeons to start proper therapy without delay.” That ability comes at a price, however. In Germany, where this study was performed, each rapid test costs about 400 Euros, which is nearly $500 US.

In a commentary on the study, Garth Ehrlich and Michael Palmer cite another possible cost with the rapid-test scenario. Prior to using any alpha defensin test, physicians must rule out metallosis with MRI, because that non-infectious entity triggers false-positive results.

What’s New in Musculoskeletal Basic Science 2017

Specialty Update Image for OBuzz

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, Matthew J. Allen, VetMB, PhD, author of the December 6, 2017 Specialty Update on Musculoskeletal Basic Science, summarized the five most compelling findings from among the more than 60 noteworthy studies summarized in the article.

Cartilage Repair

–Deriving induced pluripotent stem cells (iPSCs) from peripheral blood cells1 rather than from dermal fibroblasts obviates the need for in vitro expansion. This method may also serve to boost interest in the use of commercial cell-based therapies with defined potency that are available off-the-shelf and don’t require separate cell-harvesting procedures.

–The FDA recommends that large-animal models be used to corroborate basic-science findings from small-animal models. Recent work has demonstrated the efficacy of insulin-like growth factor (IGF)-1 in supporting mechanically competent repair tissue following chondrocyte implantation in a pig model.2

Infection

–Infection, especially from organisms that have developed antimicrobial resistance and/or that produce biofilms, continues to pose a challenging problem for orthopaedic surgeons. To provide a more rational and stratified approach to managing these complex cases, Getzlaf et al. recommend the use of a multidisciplinary approach in which patient-specific information about individual microorganisms is combined with detailed understandings of the vulnerabilities of candidate bacterial species.3

Aseptic Loosening

–There is a resurgence of interest in the role of subclinical infection in the etiopathogenesis of aseptic loosening. At the same time, molecular diagnostic methods for microbial infection are moving forward.4 Such methods may serve to highlight the relevance of subclinical microbial contamination as a cause of aseptic loosening.

Cartilage Imaging

–While the goal of cartilage imaging is to develop tools that are fast, inexpensive, sensitive, accurate, and noninvasive, there is growing interest in the use of more direct, invasive techniques such as optical coherence tomography (OCT),5 which could be used in vivo at the time of surgery to analyze cartilage damage.

References

  1. Li Y, Liu T, Van Halm-Lutterodt N, Chen J, Su Q, Hai Y. Reprogramming of blood cells into induced pluripotent stem cells as a new cell source for cartilage repair. Stem Cell Res Ther.2016 Feb 17;7:31.
  2. Meppelink AM, Zhao X, Griffin DJ, Erali R, Gill TJ, Bonassar LJ, Redmond RW,Randolph MA. Hyaline articular matrix formed by dynamic self-regenerating cartilage and hydrogels. Tissue Eng Part A.2016 Jul;22(13-14):962-70. Epub 2016 Jul 7.
  3. Getzlaf MA, Lewallen EA, Kremers HM, Jones DL, Bonin CA, Dudakovic A,Thaler R, Cohen RC, Lewallen DG, van Wijnen AJ. Multi-disciplinary antimicrobial strategies for improving orthopaedic implants to prevent prosthetic joint infections in hip and knee. J Orthop Res.2016 Feb;34(2):177-86. Epub 2015 Dec 29.
  4. Palmer MP, Melton-Kreft R, Nistico L, Hiller NL, Kim LH, Altman GT, Altman DT, Sotereanos NG, Hu FZ, De Meo PJ, Ehrlich GD. Polymerase chain reaction-electrospray-time-of-flight mass spectrometry versus culture for bacterial detection in septic arthritis and osteoarthritis. Genet Test Mol Biomarkers.2016 Dec;20(12):721-31. Epub 2016 Oct 17.
  5. Novakofski KD, Pownder SL, Koff MF, Williams RM, Potter HG, Fortier LA. High-resolution methods for diagnosing cartilage damage in vivo. 2016 Jan;7(1):39-51.

Modern Irrigation/Debridement Yields Good Results for Early Post-THA Infection

Hip Debridement for OBuzzNowadays, chronic deep periprosthetic joint infections (PJIs) are typically treated with 2-stage exchange arthroplasty, but what about acute PJIs? In the December 6, 2017 edition of JBJS, Bryan et al. report on a retrospective cohort study of acute infections after hip arthroplasty. The results suggest we’ve come a long way in identifying patients with early infections and that contemporary irrigation-and-debridement protocols are more successful than older methods.

The researchers studied 6-year outcomes in 90 hips that had undergone either total or hemiarthroplasty and that were determined to have either acute early postoperative infections (n=66) or acute hematogenous infections (n=24). All the infected hips were managed with either irrigation, debridement, and modular head and liner exchange (70%) or with irrigation and debridement alone (30%). The authors stratified the patients into those without comorbidities (A), those with 1 or 2 comorbidities (B), and those with >2 comorbidities (C). Postoperatively, patients were treated with broad-spectrum intravenous antibiotics, followed by targeted therapy administered by infectious disease specialists.

Of the 90 acute infections, failure—defined as uneradicated infection, subsequent removal of any component for infection, unplanned second wound debridement for ongoing infection, or infection-related mortality—occurred in 15 hips (17%). Of those 15, 9 required component removal. The chances of treatment failure were slightly higher in cases of hematogenous infection (21%), compared with acute early postoperative infection (15%), but that difference was not statistically significant. Significant comorbidity-related failure-rate differences were found: failure occurred in 8% of the grade-A patients, 16% of grade-B patients, and 44% of grade-C patients. The most common infecting organism was methicillin-sensitive Staphylococcus aureus (MSSA).

From this overall 6-year success rate of 83%, the authors conclude that “with modern inclusion criteria for acute infection, modern surgical techniques, and modern antibiotic therapy…the rate of success was higher than in most historic reports.”

Fructosamine Bests HbA1c for Preop Glycemic Screening

Fructosamine for OBuzzPatients with diabetes have an increased risk of postoperative complications following total joint arthroplasty (TJA). Additionally, perioperative hyperglycemia has been identified as a common and independent risk factor for periprosthetic joint infection, even among patients without diabetes. Therefore, knowing a patient’s glycemic status prior to surgery is very helpful.

In the November 15, 2017 edition of The Journal of Bone & Joint Surgery, Shohat et al. demonstrate that serum fructosamine, a measure of glycemic control obtainable via a simple and inexpensive blood test, is a good predictor of adverse outcomes among TJA patients—whether or not they have diabetes.

Researchers screened 829 patients undergoing TJA for serum fructosamine and HbA1c—a common measure, levels of which <7% are typically considered good glycemic control. Patients with fructosamine levels ≥292 µmol/L had a significantly higher risk of postoperative deep infection, readmission, and reoperation, while HbA1c levels ≥7% showed no significant correlations with any of those three adverse outcomes. Among the 51 patients who had fructosamine levels ≥292 µmol/L, 39% did not have HbA1c levels ≥7%, and 35% did not have diabetes.

In addition to being more predictive of postsurgical complications than HbA1c, fructosamine is also a more practical measurement. A high HbA1c level during preop screening could mean postponing surgery for 2 to 3 months, while the patient waits to see whether HbA1c levels come down. Fructosamine levels, on the other hand, change within 14 to 21 days, so patients could be reassessed for glycemic control after only 2 or 3 weeks.

While conceding that the ≥292 µmol/L threshold for fructosamine suggested in this study should not be etched in stone, the authors conclude that “fructosamine could serve as the screening marker of choice” for presurgical glycemic assessment. However, because the study did not examine whether correcting fructosamine levels leads to reduced postoperative complications, a prospective clinical trial to answer that question is needed.

New Hope for New Bone After Osteomyelitis Debridement

Osteomyelitis Tibia for OBuzzThis basic science tip 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.

One clinical frustration following osteomyelitis debridement is poor bone healing. Impaired bone homeostasis provokes serious variations in bone remodeling that involve multiple inflammatory cytokines.

The chemokines CCL2, CCL3, and CXCL2 are known to be strong chemoattractants for neutrophils during inflammatory states, and they play a role during osteoclastogenesis. B cells are also activators of osteoclastognesis and are regulated, in part, by tissue inhibitor of metalloprotease 1 (TIMP-1).

Researchers drilled a 1 mm hole into the proximal tibia of 126 mice. In half of the mice (63), a dose of S. aureus was injected into the canal, while the controls had no bacteria injected. At two weeks, all proximal tibiae were debrided; cultures were taken 3 and 7 days after debridement to assure no residual infection. Cytokine assays and Western blots for CCL2, CCL3, CXCL2, TIMP-1, RANKL, and TNF-α were performed in selected mice in each group. Flow cytometry and histology were also done in selected mice in each group.

In the osteomyelitis group, Western blot analysis identified increased levels of CCL2, CCL3, and CXCL2. Histology revealed increased osteoclastogenesis after osteomyelitis debridement, with calcitonin-receptor and RANKL detection via immunohistochemical and fluorescence staining. There was diminished osteogenesis and proliferation in the osteomyelitis group, but TNF-α expression seemed to have no effect on altered bone regeneration after bone infection. Flow cytometry revealed elevated B cell activity in the osteomyelitis group, with subsequent increased osteoclast activity and accelerated bone resorption.

The researchers propose a RANKL-dependent osteoclastogenesis after debridement for osteomyelitis that is associated with elevated B cells and decreased osteogenesis. These findings could lead to new interventions to improve bone healing during the course of osteomyelitis treatment, particularly following debridement.

Reference
Wagner JM, Jaurich H, Wallner C, Abraham S, Becerikli M, Dadras M, Harati K, Duhan V, Khairnar V, Lehnhardt M, Behr B. Diminished bone regeneration after debridement of posttraumatic osteomyelitis is accompanied by altered cytokine levels, elevated B cell activity, and increased osteoclast activity. J Orthop Res. 2017 Mar 6. doi: 10.1002/jor.23555. [Epub ahead of print] PMID: 28263017

D-Dimer Levels May Help with PJI Diagnoses

D-dimer for OBuzzThe percentage of periprosthetic joint infections (PJIs) among patients requiring revision arthroplasty of the hip and knee is increasing. PJIs have important clinical implications both for revision surgical procedures as well as pre- and postoperative management. Any extra help we can get making a PJI diagnosis outside of the obvious (where the patient presents with a draining wound) would be most welcome.

In the September 6, 2017 issue of The Journal, Shahi et al. present compelling data from a prospective study suggesting that serum D-dimer levels may help diagnose PJI—and thereby help determine the optimal timing of component reimplantation. The authors determined that 850 ng/mL was the optimal threshold value for D-dimer in diagnosing PJI. Moreover, with sensitivity of 89% and specificity of 93%, this test outperformed the widely used ESR and CRP tests, which until now have proven to be the “best” tools we have at our disposal.

Ideally, after these results are confirmed in larger populations of patients undergoing revision arthroplasty, the serum D-dimer test—inexpensive and almost universally available—will be used in all high-volume joint replacement centers. The continued pursuit of diagnostic and treatment methodologies for patients with suspected PJI is definitely warranted, given the increasing number of patients requiring arthroplasty and combined lifetime knee- and hip-replacement revision rates hovering around 10% to 12%. The identification of D-Dimer elevation as a potentially more accurate diagnostic tool than our currently available tests is a welcome contribution.

Marc Swiontkowski, MD
JBJS Editor-in-Chief

What’s New in Musculoskeletal Infection

PPI Image for O'BuzzEvery 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, Arvind Nana, MD, co-author of the July 19, 2017 Specialty Update on musculoskeletal infection, selected the five most compelling findings from among the more than 120 studies cited in the Specialty Update.

Periprosthetic Joint Infection

–Much of the discussion around treating periprosthetic joint infections (PJIs) centers around comparing one-stage versus two-stage exchange arthroplasty. Two-stage exchange arthroplasty requires the use of a temporary cement spacer, and one study1 found that debris from articulating spacers may induce CD3, CD20, CD11(c), and IL-17 changes, raising the possibility of associated immune modulation.

–When performing debridement to treat a PJI, instead of an irrigation solution containing antibiotics, a 20-minute antiseptic soak with 0.19% vol/vol acetic acid reduced the risk of reinfection.2

Spine

–Four studies helped bolster evidence that surgical-site infections are the leading cause of reoperations after spine surgery, both early (within 30 days)3, 4 and late (after 2 years).5, 6

Trauma

–A 100-patient prospective cohort study found that posttraumatic osteomyelitis treated with a 1-stage protocol and host optimization in Type B hosts resulted in 96% infection-free outcomes.7

Shoulder

–As in lower-extremity procedures, the risk of infection after shoulder arthroplasty and arthroscopy is higher when the surgeries are performed less than 3 months after a corticosteroid injection. This finding suggests elective shoulder procedures should be delayed for at least 90 days after such injections.8

References

  1. Singh G, Deutloff N, Maertens N, Meyer H, Awiszus F, Feuerstein B, Roessner A, Lohmann CH. Articulating polymethylmethacrylate (PMMA) spacers may have an immunomodulating effect on synovial tissue. Bone Joint J. 2016 ;98-B(8):1062–8.
  2. Williams RL, Ayre WN, Khan WS, Mehta A, Morgan-Jones R. Acetic acid as part of a debridement protocol during revision total knee arthroplasty. J Arthroplasty. 2017 ;32(3):953–7. Epub 2016 Sep 28.
  3. Medvedev G, Wang C, Cyriac M, Amdur R, O’Brien J. Complications, readmissions, and reoperations in posterior cervical fusion. Spine (Phila Pa 1976). 2016 ;41(19):1477–83.
  4. Hijas-Gómez AI, Egea-Gámez RM, Martínez-Martín J, González-Díaz RC, Losada-Viñas JI, Rodríguez-Caravaca G. Surgical wound infection rates and risk factors in spinal fusion in a university teaching hospital in Madrid, Spain. Spine. November 2016.
  5. Ohya J, Chikuda H, Takeshi O, Kato S, Matsui H, Horiguchi H, Tanaka S, Yasunaga H. Seasonal variations in the risk of reoperation for surgical site infection following elective spinal fusion surgery: a retrospective study using the Japanese diagnosis procedure combination database. Spine (Phila Pa 1976). 2016 . Epub 2016 Nov 22.
  6. Ahmed SI, Bastrom TP, Yaszay B, Newton PO; Harms Study Group. 5-year reoperation risk and causes for revision after idiopathic scoliosis surgery. Spine (Phila Pa 1976). 2016 . Epub 2016 Nov 9.
  7. McNally MA, Ferguson JY, Lau ACK, Diefenbeck M, Scarborough M, Ramsden AJ, Atkins BL. Single-stage treatment of chronic osteomyelitis with a new absorbable, gentamicin-loaded, calcium sulphate/hydroxyapatite biocomposite: a prospective series of 100 cases. Bone Joint J. 2016 ;98-B(9):1289–96.
  8. Werner BC, Cancienne JM, Burrus MT, Griffin JW, Gwathmey FW, Brockmeier SF. The timing of elective shoulder surgery after shoulder injection affects postoperative infection risk in Medicare patients. J Shoulder Elbow Surg. 2016 ;25(3):390–7. Epub 2015 Nov 30.

JBJS Editor’s Choice—Knee Sepsis: Arthroscopic or Open Treatment?

Open vs Arthroscopic Tx for Knee Sepsis.jpegIn the March 15, 2017 issue of The Journal, Johns et al. report results from a Level III cohort study comparing arthroscopic vs open irrigation for control of acute native-knee sepsis. The authors collected information on more than 160 patients with knee sepsis over a 15-year period, which is a large cohort of patients with this relatively unusual clinical problem.

The data show a cumulative success rate of 97% with arthroscopic treatment after 3 irrigations and debridements vs 83% success in the arthrotomy group after the same number of procedures—a clinically important difference. Significantly fewer arthroscopic procedures were required for successful treatment, relative to open procedures, and post-procedure median knee range of motion was significantly greater in the arthroscopic group (90°) than in the open treatment group (70°).

The fact is that arthroscopic instruments allow a greater volume of irrigation fluid to be instilled with better access to the posterior recesses of the knee. With an open arthrotomy, it is more difficult to irrigate with high volumes, and the posterior recesses of the knee are not well accessed. It seems clear that arthroscopic management of acute knee sepsis should be the standard of care for these reasons, as well as because the technique is minimally invasive in terms of soft tissue stripping and incision size.

Treating infections of major-weight bearing joints is following a trend seen in surgical management of many orthopaedic conditions—smaller exposures with use of adjunctive visualization techniques.

Marc Swiontkowski, MD
JBJS Editor-in-Chief

Smoking Boosts Rate of Reoperation for Infection after TJA

Smoking Image from Nick.jpegHere’s one thing about which medical studies have been nearly unanimous:  Smoking is a health hazard by any measure. In the February 15, 2017 edition of The Journal of Bone & Joint Surgery, Tischler et al. put some hard numbers on the risk of smoking for those undergoing total joint arthroplasty (TJA).

After controlling for confounding factors, the authors of the Level III prognostic study found that:

  • Current smokers have a significantly increased risk of reoperation for infection within 90 days of TJA compared with nonsmokers.
  • The amount one has smoked, regardless of current smoking status, significantly contributed to increased risk of unplanned nonoperative readmission.

In a commentary on the Tischler et al. study, William, G. Hamilton, MD says, “…as physicians, we should work cooperatively with our patients to enhance outcomes by attempting to reduce these modifiable risk factors. We can educate patients and can suggest smoking cessation programs and weight loss regimens that may not only improve the risk profile during the surgical episode, but also improve the patients’ overall health.”