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Diabetic foot ulcers are frequent with average lifetime risk of 15%, and can lead to bone and joint infections. Current protocols for their management include evaluation of ischemia, assessment of underlying bone infection, sharp debridement, off-loading and use of dressings that promote moist wound healing. Extensive debridement is optimal for wound healing and decreases the risk of recurrence. However, extension of surgical debridement is left at the clinician judgement and thus lacks standardised protocols. Plus, there is currently no known risk factors or specific biomarkers that can help guide the clinician for the extent of debridement or that can predict a recurrence in case of non-extensive debridement. The main objectives of the study are to either unravel a new biomarker, and/or identify risk factors associated with poor prognosis following surgical debridement in diabetic foot ulcers. Histones, more specifically H3.1 subtype, have been associated with sepsis.
The main hypothesis is that higher blood levels of H3.1 will be present in participants showing poor prognosis (i.e., having additional surgeries, amputation, death) and that a rise in H3.1 blood levels compared to baseline (before the 1st surgical intervention) would provide an early warning of relapse or treatment failure.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Diabetic foot ulcer with osteoarticular infections | Diabetic patients suffering from ulcer that led to an osteoarticular infection (e.g. chronic osteomyelitis, septic arthritis) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Histones H3.1 blood levels | Diagnostic Test | Measure of blood concentrations of histone subtype H3.1 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Clinical failure | Presence of infection (IWGDF 2019 criteria) and No change in H3.1 blood levels from baseline (day -1) or secondary increase after an initial decline ≥ 75% | day 30 and day 60 |
| Measure | Description | Time Frame |
|---|---|---|
| Mortality | Death during the study period from day-1 (day of the 1st intervention) | day 30 and day 60 |
| Amputation rate | Frequency of the event 'amputation' as incidence rate from day-1 (day of the 1st intervention) |
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Inclusion Criteria:
Exclusion Criteria:
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All diabetic patients fulfilling the inclusion criteria with no exclusion criteria.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospitals Geneva | Geneva | 1211 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32176445 | Background | Monteiro-Soares M, Russell D, Boyko EJ, Jeffcoate W, Mills JL, Morbach S, Game F; International Working Group on the Diabetic Foot (IWGDF). Guidelines on the classification of diabetic foot ulcers (IWGDF 2019). Diabetes Metab Res Rev. 2020 Mar;36 Suppl 1:e3273. doi: 10.1002/dmrr.3273. | |
| 20840517 | Background |
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| ID | Term |
|---|---|
| D017719 | Diabetic Foot |
| D001170 | Arthritis, Infectious |
| ID | Term |
|---|---|
| D003925 | Diabetic Angiopathies |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D016523 | Foot Ulcer |
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Centrifugated blood samples (serum/plasma used for analyses)
| day 1 to day 60 |
| Additional surgical interventions rate | Frequency of the event 'additional surgical intervention' (i.e., debridement, amputation) as incidence rate from day-1 (day of the 1st intervention) | day 1 to day 60 |
| Time-to-amputation | Measured in days from day-1 (day of the 1st intervention) | day 1 to day 60 |
| Time-to-additional-intervention | Measured in days from day-1 (day of the 1st intervention) | day 1 to day 60 |
| Lebrun E, Tomic-Canic M, Kirsner RS. The role of surgical debridement in healing of diabetic foot ulcers. Wound Repair Regen. 2010 Sep-Oct;18(5):433-8. doi: 10.1111/j.1524-475X.2010.00619.x. |
| 32170015 | Background | Thiam HR, Wong SL, Qiu R, Kittisopikul M, Vahabikashi A, Goldman AE, Goldman RD, Wagner DD, Waterman CM. NETosis proceeds by cytoskeleton and endomembrane disassembly and PAD4-mediated chromatin decondensation and nuclear envelope rupture. Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7326-7337. doi: 10.1073/pnas.1909546117. Epub 2020 Mar 13. |
| 26076037 | Background | Wong SL, Demers M, Martinod K, Gallant M, Wang Y, Goldfine AB, Kahn CR, Wagner DD. Diabetes primes neutrophils to undergo NETosis, which impairs wound healing. Nat Med. 2015 Jul;21(7):815-9. doi: 10.1038/nm.3887. Epub 2015 Jun 15. |
| 21878229 | Background | Li Y, Liu B, Fukudome EY, Lu J, Chong W, Jin G, Liu Z, Velmahos GC, Demoya M, King DR, Alam HB. Identification of citrullinated histone H3 as a potential serum protein biomarker in a lethal model of lipopolysaccharide-induced shock. Surgery. 2011 Sep;150(3):442-51. doi: 10.1016/j.surg.2011.07.003. |
| 33790693 | Background | Eichhorn T, Linsberger I, Laukova L, Tripisciano C, Fendl B, Weiss R, Konig F, Valicek G, Miestinger G, Hormann C, Weber V. Analysis of Inflammatory Mediator Profiles in Sepsis Patients Reveals That Extracellular Histones Are Strongly Elevated in Nonsurvivors. Mediators Inflamm. 2021 Mar 17;2021:8395048. doi: 10.1155/2021/8395048. eCollection 2021. |
| 36008932 | Background | Morimont L, Dechamps M, David C, Bouvy C, Gillot C, Haguet H, Favresse J, Ronvaux L, Candiracci J, Herzog M, Laterre PF, De Poortere J, Horman S, Beauloye C, Douxfils J. NETosis and Nucleosome Biomarkers in Septic Shock and Critical COVID-19 Patients: An Observational Study. Biomolecules. 2022 Jul 27;12(8):1038. doi: 10.3390/biom12081038. |
| D007871 |
| Leg Ulcer |
| D012883 | Skin Ulcer |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D048909 | Diabetes Complications |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
| D003929 | Diabetic Neuropathies |
| D007239 | Infections |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |