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Residual Infection After Forefoot Amputation in Diabetic Foot Infection: Is New Information Helpful Even When Negative?

Sangeorzan, Bruce J. MD

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The Journal of Bone and Joint Surgery: September 5, 2018 - Volume 100 - Issue 17 - p 1447
doi: 10.2106/JBJS.18.00593
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In their paper, “Culture of Bone Biopsy Specimens Overestimates Rate of Residual Osteomyelitis After Toe or Forefoot Amputation,” published in this issue of JBJS, Mijuskovic et al. address a difficult diagnostic problem—i.e., whether there is residual bone infection after an amputation involving the forefoot. During a 2-year period, clinicians acquired culture and tissue biopsy specimens from the site of the residual bone after completion of an amputation in 51 patients. The decisions to perform surgery and regarding the level of the surgery were made clinically. In this paper, as well as in most clinical scenarios, those decisions are not rigidly based on clear and discrete measures.

Both pathological and culture findings were compared with clinical outcome assessed 2 years postoperatively. While nearly two-thirds of the patients had a positive culture, only 27% showed histological signs of infection. Both culture and histological findings were positive in 24% of the cases. The authors speculated, not unreasonably, that the false-positive findings may be related to cross-contamination. They did not report how the markers of infection affected treatment decisions.

Some aspects of this paper, such as the nuance of a positive pathological diagnosis and the interpretation of multiple organisms grown on culture from specimens from an open wound, are outside the knowledge and comfort zone of many orthopaedic surgeons. Yet orthopaedic surgeons are drawn into the discussion when surgery is deemed necessary or bone biopsy and culture are requested, and most face uncertainty when selecting an amputation level.

Practice guidelines for infections of the foot related to diabetes are based in part on bone biopsy1. The authors of this widely cited guideline explicitly stated that infection is “difficult to diagnose … {and} optimally defined by bone culture and histology.” They proposed recommendations based on these biopsies as well as on legacy assessment instruments to grade the wounds. Others have acknowledged the shortcomings of evidence, recognizing that there is “only limited high-quality evidence for many of the critical questions.”2

The JBJS review process is multidisciplinary and robust. Consultants with expertise in surgery, infection, and pathology were engaged in the review of this paper, and there were strong differences among them regarding whether the paper should be published. It is likely that both clinical discipline and personal experience had an impact on the reviews. Negative results are not often published as reviewers are not likely to be enthusiastic about publishing a lack of treatment effect or to see value in negative data that do not help support guidelines3,4. The conclusions of this study are largely negative. One cannot support or refute the current guidelines for diabetic foot infection. Readers are likely to interpret these data differently. There are 2 conclusions that may be agreed on. First, information gained from biopsy of bone may not be the gold standard that it is believed to be. Second, in the absence of a gold standard, the surgical treatment of infection in patients with morbid diabetes is best provided by a multidisciplinary team with different perspectives and a willingness to work together to help patients. It is our sincere hope that publishing this manuscript will stimulate further high-quality research in this area of high clinical need.

Disclosure: The author indicated that no external funding was received for any aspect of this work. The Disclosure of Potential Conflicts of Interest form is provided with the online version of the article (


1. Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG, Deery HG, Embil JM, Joseph WS, Karchmer AW, Pinzur MS, Senneville E; Infectious Diseases Society of America. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012 Jun;54(12):e132-73.
2. Hingorani A, LaMuraglia GM, Henke P, Meissner MH, Loretz L, Zinszer KM, Driver VR, Frykberg R, Carman TL, Marston W, Mills JL Sr, Murad MH. The management of diabetic foot: a clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine. J Vasc Surg. 2016 Feb;63(2)(Suppl):3S-21S.
3. Hopewell S, Loudon K, Clarke MJ, Oxman AD, Dickersin K. Publication bias in clinical trials due to statistical significance or direction of trial results. Cochrane Database Syst Rev. 2009 Jan 21;1:MR000006.
4. Fanelli D. Negative results are disappearing from most disciplines and countries. Scientometrics. 2012 Mar;90(3):891-904.

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