Cho NH, Shaw JE, Karuranga S, et al: IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 138: 271, 2018.
Singh N, Armstrong DG, Lipsky BA: Preventing foot ulcers in patients with diabetes. JAMA 293: 217, 2005.
Hussain Z, Thu HE, Shuid AN, et al: Recent Advances in Polymer-based Wound Dressings for the Treatment of Diabetic Foot Ulcer: An Overview of State-of-the-art. Curr Drug Targets 19: 527, 2018.
Endris T, Worede A, Asmelash D: Prevalence of diabetes mellitus, prediabetes and its associated factors in Dessie town, Northeast Ethiopia: A community-based study. Diabetes Metab Syndr Obes 12: 2799, 2019.
Lipsky BA, Peters EJ, Senneville E, et al: Expert opinion on the management of infections in the diabetic foot. Diabetes Metab Res Rev 28: 163, 2012.
Van Asten SA, Nichols A, La Fontaine J, et al: The value of inflammatory markers to diagnose and monitor diabetic foot osteomyelitis. Int Wound J 14: 40, 2017.
Altay FA, Sencan İ, Şentürk G, et al: Does treatment affect the levels of serum interleukin-6, interleukin-8 and procalcitonin in diabetic foot infection? A pilot study. J Diabetes Complications 26: 214, 2012.
Fleischer AE, Didyk AA, Woods JB, et al: Combined clinical and laboratory testing improves diagnostic accuracy for osteomyelitis in the diabetic foot. J Foot Ankle Surg 48: 39, 2009.
Jeandrot A, Richard JL, Combescure C, et al: Serum procalcitonin and C-reactive protein concentrations to distinguish mildly infected from non-infected diabetic foot ulcers: a pilot study. Diabetologia 51: 347, 2008.
Michail M, Jude E, Liaskos C, et al: The performance of serum inflammatory markers for the diagnosis and follow-up of patients with osteomyelitis. Int J Low Extrem Wounds 12: 94, 2013.
Uzun G, Solmazgul E, Curuksulu H, et al: Procalcitonin as a diagnostic aid in diabetic foot infections. Tohoku J Exp Med 213: 305, 2007.
Yamada S, Maruyama I: HMGB1, a novel inflammatory cytokine. Clin Chim Acta 375: 36, 2007.
Yang H, Tracey KJ: High mobility group box 1 (HMGB1). Crit Care Med 33: S472, 2005.
Alsousi AA, Igwe OJ: Redox-active trace metal-induced release of high mobility group box 1(HMGB1) and inflammatory cytokines in fibroblast-like synovial cells is Toll-like receptor 4 (TLR4) dependent. Biochim Biophys Acta Mol Basis Dis 1864: 3847, 2018.
Giannoudis PV, Mallina R, Harwood P, et al: Pattern of release and relationship between HMGB-1 and IL-6 following blunt trauma. Injury 41: 1323, 2010.
Yamada S, Yakabe K, Ishii J, et al: New high mobility group box 1 assay system. Clin Chim Acta 372: 173, 2006.
Lipsky BA, Berendt AR, Cornia PB, et al: 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 54: e132, 2012.
Lavery LA, Armstrong DG, Wunderlich RP, et al: Risk factors for foot infections in individuals with diabetes. Diabetes Care 29: 1288, 2006.
Senneville E, Lombart A, Beltrand E, et al: Outcome of diabetic foot osteomyelitis treated nonsurgically: a retrospective cohort study. Diabetes Care 31: 637, 2008.
Lavery LA, Peters EJ, Armstrong DG, et al: Risk factors for developing osteomyelitis in patients with diabetic foot wounds. Diabetes Res Clin Pract 83: 347, 2009.
Mutluoglu M, Sivrioglu AK, Eroglu M, et al: The implications of the presence of osteomyelitis on outcomes of infected diabetic foot wounds. Scand J Infect Dis 45: 497, 2013.
Lipsky BA, Aragón-Sánchez J, Diggle M, et al: IWGDF guidance on the diagnosis and management of foot infections in persons with diabetes. Diabetes Metab Res Rev 32: 45, 2016.
Markanday A: Diagnosing diabetic foot osteomyelitis: narrative review and a suggested 2-step score-based diagnostic pathway for clinicians. Open Forum Infect Dis 1: ofu060, 2014.
Devillers A, Moisan A, Hennion F, et al: Contribution of technetium-99m hexamethylpropylene amine oxime labelled leucocyte scintigraphy to the diagnosis of diabetic foot infection. Eur J Nucl Med 25: 132, 1998.
Johnson JE, Kennedy EJ, Shereff MJ, et al: Prospective study of bone, indium-111-labeled white blood cell, and gallium-67 scanning for the evaluation of osteomyelitis in the diabetic foot. Foot Ankle Int 17: 10, 1996.
Palestro CJ, Caprioli R, Love C, et al: Rapid diagnosis of pedal osteomyelitis in diabetics with a technetium-99m-labeled monoclonal antigranulocyte antibody. J Foot Ankle Surg 42: 2, 2003.
Palestro CJ, Love C: Nuclear medicine and diabetic foot infections. Semin Nucl Med 39: 52, 2009.
Brownrigg JR, Schaper NC, Hinchliffe RJ: Diagnosis and assessment of peripheral arterial disease in the diabetic foot. Diabet Med 32: 738, 2015.
Prompers L, Huijberts M, Apelqvist J, et al: High prevalence of ischaemia, infection and serious comorbidity in patients with diabetic foot disease in Europe. Baseline results from the Eurodiale study. Diabetologia 50: 18, 2007.
Baykal YB, Yaman E, Burc H, et al: Is scintigraphy a guideline method in determining amputation levels in diabetic foot? JAPMA 104: 227, 2014.
Schauwecker DS: The scintigraphic diagnosis of osteomyelitis. AJR Am J Roentgenol 158: 9, 1992.
Ertugrul BM, Savk O, Ozturk B, et al: The diagnosis of diabetic foot osteomyelitis: examination findings and laboratory values. Med Sci Monit 15: Cr307, 2009.
Mutluoğlu M, Uzun G, İpcioğlu OM, et al: Can procalcitonin predict bone infection in people with diabetes with infected foot ulcers? A pilot study. Diabetes Res Clin Pract 94: 53, 2011.
Butalia S, Palda VA, Sargeant RJ, et al: Does this patient with diabetes have osteomyelitis of the lower extremity? JAMA 299: 806, 2008.
Lipsky BA, Berendt AR: Principles and practice of antibiotic therapy of diabetic foot infections. Diabetes Metab Res Rev 16: S42, 2000.
Armstrong DG, Lavery LA, Vazquez JR, et al: How and why to surgically debride neuropathic diabetic foot wounds. JAPMA 92: 402, 2002.
Grigoropoulou P, Eleftheriadou I, Jude EB, et al: Diabetic foot infections: an update in diagnosis and management. Curr Diab Rep 17: 3, 2017.
Lipsky BA, Berendt AR, Cornia PB, et al: 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. JAPMA 103: 2,2013.
Peters EJ: Pitfalls in diagnosing diabetic foot infections. Diabetes Metab Res Rev 32: 254, 2016.
Lipsky BA, Senneville É, Abbas ZG, et al: Guidelines on the diagnosis and treatment of foot infection in persons with diabetes (IWGDF 2019 update). Diabetes Metab Res Rev 36: e3280, 2020.
Background: The incidence of diabetic foot infections is increasing due to the rising number of persons with diabetes and the prolonged life expectancy. It is vital to differentiate soft-tissue infection (STI) from diabetic foot osteomyelitis (DFO), as treatment modalities and durations vary widely, but this can be challenging. We aimed to assess the blood concentration levels of the high mobility group box 1 protein (HMGB-1) in STI and DFO compared to healthy subjects, and to investigate whether this protein could contribute to differentiating STI from DFO.
Methods: Data from patients with suspected soft-tissue infection or diabetic foot osteomyelitis and healthy volunteers were prospectively recorded. Mean C-reactive protein, erythrocyte sedimentation rate, white blood cell, and HMGB-1 values in the groups were analyzed. Cut-off values of HMGB-1 between the three groups were also determined. A three-phase bone scintigraphy was accepted as the diagnostic method for differentiating STI and DFO.
Results: A total of 92 volunteers, were included in the study. Group 1 comprised 28 healthy individuals who composed the control group. Group 2 comprised the 35 patients diagnosed with STI, and Group 3 comprised 29 patients diagnosed with DFO. The HMGB-1 was significantly higher in DFO. The sensitivity, specificity, and accuracy of HMGB-1 in differentiating between STI and DFO was 55%, 94%, and 77%, respectively.
Conclusions: We concluded that measurement of the serum HMGB-1 level could be an adjunctive test in the differential diagnosis of diabetic foot infections.