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Oxygenation Status in Chronic Leg Ulcer After Topical Hemoglobin Application May Act as a Surrogate Marker to Find the Best Treatment Strategy and to Avoid Ineffective Conservative Long-term Therapy

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Abstract

Purpose

Chronic leg ulcers can be a challenge to treat and long-term therapy a significant cost factor in western public health budgets. Objective wound assessment assays enabling selection of appropriate wound therapy regimes would be desirable. Oxygenation status in ulcer tissue has obtained increased attention as a relevant factor in wound healing. To increase oxygenation in wounds, a topical hemoglobin spray was developed. Although favorable results have been noted, the link between clinical efficacy and the mode of action has not been demonstrated. The aims were to determine if changes in tissue oxygenation can be measured after topical application of hemoglobin on chronic wounds and to evaluate the findings in terms of therapy strategies.

Procedures

Photoacoustic imaging was used to measure the local oxygen saturation (StO2) in leg ulcers before and after hemoglobin spray treatment. Sclerosis of the leg ulcers was histopathologically graded and the change in wound size was documented in a follow-up examination.

Results

Measuring 49 patients, an increase in StO2 after topical hemoglobin application from on average 66.1 to 71 % (p = 0.017) after 20 min was observed. Depending on the increase in StO2 (>10 % or <10 %) patients were stratified into a Responder and a Non-Responder group. Wound size significantly decreased in the Responder Group (p = 0.001), while no significant difference in the Non-Responder group (p = 0.950) was noted.

Conclusion

Our findings suggest that the likelihood of wound healing under conservative therapy can be predicted by measuring changes in StO2 after topical hemoglobin application. This assay may reduce treatment time and costs by avoiding ineffective conservative long-term therapy.

Trial Registration

German Clinical Trials Register: DRKS00005993

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References

  1. Fowkes FG, Evans CJ, Lee AJ (2001) Prevalence and risk factors of chronic venous insufficiency. Angiology 52(Suppl 1):S5–15

    Article  PubMed  Google Scholar 

  2. Margolis DJ, Cohen JH (1994) Management of chronic venous leg ulcers: a literature-guided approach. Clin Dermatol 12:19–26

    Article  CAS  PubMed  Google Scholar 

  3. Posnett J, Franks PJ (2008) The burden of chronic wounds in the UK. Nurs Times 104:44–45

    PubMed  Google Scholar 

  4. Augustin M, Brocatti LK, Rustenbach SJ et al (2014) Cost-of-illness of leg ulcers in the community. Int Wound J 11:283–292

    Article  PubMed  Google Scholar 

  5. Fox JD, Baquerizo Nole KL, Berriman SJ et al (2016) Chronic wounds: the need for greater emphasis in medical schools, post-graduate training and public health discussions. Ann Surg 264:241–243

    Article  PubMed  Google Scholar 

  6. Dissemond J, Bultemann A, Gerber V et al (2016) Definitions for wound treatment. Hautarzt 67:265–266

    Article  CAS  PubMed  Google Scholar 

  7. Schreml S, Meier RJ, Kirschbaum M et al (2014) Luminescent dual sensors reveal extracellular pH-gradients and hypoxia on chronic wounds that disrupt epidermal repair. Theranostics 4:721–735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Korber A, Klode J, Al-Benna S et al (2011) Etiology of chronic leg ulcers in 31,619 patients in Germany analyzed by an expert survey. J Dtsch Dermatol Ges 9:116–121

    PubMed  Google Scholar 

  9. Heng MC (1993) Topical hyperbaric therapy for problem skin wounds. J Dermatol Surg Oncol 19:784–793

    Article  CAS  PubMed  Google Scholar 

  10. Tawfick WA, Sultan S (2013) Technical and clinical outcome of topical wound oxygen in comparison to conventional compression dressings in the management of refractory nonhealing venous ulcers. Vasc Endovasc Surg 47:30–37

    Article  Google Scholar 

  11. Thackham JA, McElwain DL, Long RJ (2008) The use of hyperbaric oxygen therapy to treat chronic wounds: a review. Wound Repair Regen 16:321–330

    Article  PubMed  Google Scholar 

  12. Arenbergerova M, Engels P, Gkalpakiotis S et al (2013) Topical hemoglobin promotes wound healing of patients with venous leg ulcers. Hautarzt 64:180–186

    Article  CAS  PubMed  Google Scholar 

  13. Petri M, Stoffels I, Jose J et al (2016) Photoacoustic imaging of real-time oxygen changes in chronic leg ulcers after topical application of a haemoglobin spray: a pilot study. J Wound Care 25:87–91

    Article  CAS  PubMed  Google Scholar 

  14. Ntziachristos V, Razansky D (2010) Molecular imaging by means of multispectral optoacoustic tomography (MSOT). Chem Rev 110:2783–2794

    Article  CAS  PubMed  Google Scholar 

  15. Wang LV (2008) Prospects of photoacoustic tomography. Med Phys 35:5758–5767

    Article  PubMed  PubMed Central  Google Scholar 

  16. Mallidi S, Luke GP, Emelianov S (2011) Photoacoustic imaging in cancer detection, diagnosis, and treatment guidance. Trends Biotechnol 29:213–221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Barnikol WKR, Wahler W (1978) Eine verbesserte Modifikation der Mikromethode nach Niesel und Thews (1961) zur Messung von O2-Hb-Bindungskurven in Vollblut und konzen-trierten Hb-Lösungen. Respiration 36:86–95

    Article  CAS  PubMed  Google Scholar 

  18. Döhring W, Diefenthaler K, Barnikol WKR (1973) The production and application of 0.2 to 1.0 μ thick polytetrafluorethylene membranes to continuous polarographic measurement of oxygen tension in the gas phase. Oxygen supply: theoretical and practical aspects of oxygen supply and microcirculation of tissues. 86–91

  19. Dissemond J, Augustin M, Eming SA et al (2014) Modern wound care—practical aspects of non-interventional topical treatment of patients with chronic wounds. J Deutschen Dermatol Gesellschaft 12:541–554

    Google Scholar 

  20. Needles A, Heinmiller A, Sun J et al (2013) Development and initial application of a fully integrated photoacoustic micro-ultrasound system. IEEE Trans Ultrason Ferroelectr Freq Control 60:888–897

    Article  PubMed  Google Scholar 

  21. Xia J, Yao J, Wang LV (2014) Photoacoustic tomography: principles and advances. Electromagn Waves (Camb) 147:1–22

    Article  Google Scholar 

  22. Wang X, Xie X, Ku G et al (2006) Noninvasive imaging of hemoglobin concentration and oxygenation in the rat brain using high-resolution photoacoustic tomography. J Biomed Opt 11:024015

    Article  PubMed  Google Scholar 

  23. Mooij MC, Huisman LC (2016) Chronic leg ulcer: does a patient always get a correct diagnosis and adequate treatment? Phlebology 31(1 Suppl):68–73

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank VisualSonics Fujifilm for providing us with the VEVO LAZR System for the conducted measurements and Sastomed for providing us with the hemoglobin spray. We thank Ms. M. Kretschmer for reliable technical assistance in performing the in vitro suitability tests.

Author information

Authors and Affiliations

  1. Department of Dermatology, Venerology and Allergology, University-Hospital Essen, University of Duisburg-Essen, Essen, Germany

    Maximilian Petri, Ingo Stoffels, Klaus Griewank, Andrea Schulz, Philipp Jansen, Dirk Schadendorf, Joachim Dissemond & Joachim Klode

  2. FUJIFILM VisualSonics Inc., Amsterdam, The Netherlands

    Jithin Jose

  3. Sastomed, Georgsmarienhütte, Germany

    Peter Engels

  4. SanguiBioTech, Witten, Germany

    Harald Pötzschke

Authors
  1. Maximilian Petri
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  2. Ingo Stoffels
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  3. Klaus Griewank
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  4. Jithin Jose
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  5. Peter Engels
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  6. Andrea Schulz
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  7. Harald Pötzschke
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  8. Philipp Jansen
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  9. Dirk Schadendorf
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  10. Joachim Dissemond
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  11. Joachim Klode
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Corresponding author

Correspondence to Joachim Klode.

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Funding

This study was funded by SastoMed GmbH.

Conflict of Interest

Prof. Dissemond received honorarium for lectures, advisory boards and/or clinical studies from the following companies: 3 M, B. Braun, BSN, Coloplast, Convatec, Draco, Hartmann, KCI, Lohmann&Rauscher, Medoderm, Merz, Sastomed, Systagenix, UCB-Pharma, Urgo. Dr. Engels reports personal fees from Sastomed GmbH, during the conduct of the study and personal fees from Sastomed GmbH, outside the submitted work. Prof. Schadendorf received consultancy fees, having board membership, and receiving lecture fees from GlaxoSmithKline, Novartis, Amgen, Bristol-Myers Squibb, Roche, Genentech, Boehringer Ingelheim and MSD. Dr. Klode received research grants from the following companies: VisualSonics, Sastomed, FujiFilm. All other authors declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.

Ethical Approval

This open interventional trial was approved by the institutional review board at the University Hospital Essen (13-5687-BO) and registered at the German Clinical Trials Register (DRKS00005993). All experimental procedures were in accordance with the principles laid down in the Declaration of Helsinki.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

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Petri, M., Stoffels, I., Griewank, K. et al. Oxygenation Status in Chronic Leg Ulcer After Topical Hemoglobin Application May Act as a Surrogate Marker to Find the Best Treatment Strategy and to Avoid Ineffective Conservative Long-term Therapy. Mol Imaging Biol 20, 124–130 (2018). https://doi.org/10.1007/s11307-017-1103-9

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  • DOI: https://doi.org/10.1007/s11307-017-1103-9

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