Identification of prognostic markers of chronic venous ulcers by the study of host – microbiome interplay, using non – invasive methods and high – throughout ‘OMIC’ approach
Summary: Chronic venous leg ulcers (CVLU) have a significant impact on patients’ quality of life, as well as on the healthcare system, requiring frequent hospitalizations and expensive treatments. Moreover, the development of resistance to antibiotics and antiseptics by the microorganisms that colonize ulcers lead to an alarming epidemiological risk. The etiopathogenesis of CVLU is complex and involves a multifaceted interplay of biochemical, immunological, hematological, and microbiological interactions. Wound colonization with pathogenic bacteria and consequently the development of microbial biofilms lead to CVLU chronic infections and a persistent low-grade inflammation. These processes are associated with a delay in healing and CVLU chronicity. The determination of prognostic markers (bacterial virulence and resistance markers, host inflammatory markers and others) could give the clinician the ability to modify treatment accordingly and to take advantage of therapeutic „windows of opportunity”. We aim to conduct a prospective, observational, cohort study, using an ”OMICS” based approach and non-invasive sampling methods, to investigate of the bacterial consortium of CVLU (species diversity, virulence and resistance to antibiotics of the strains), as well as the consecutive host inflammatory response reflected in wound fluid composition. The discovery of clinical- biological correlations, as well as of potential prognostic wound healing biomarkers could guide towards a personalized and more efficient therapeutic approach.
Project code: PN-III-P1-1.1-PD-2019-1225
Contract no: PD 167/ 2020
Acronym: ULCEROMICS
Contract start date: 01.09.2020
Date of conclusion of the contract: 31.10.2023
Duration: 24 months (2020-2023). Contract suspended from 01.08.2021 to 31.07.2022 (maternity leave, child growth leave).
Project Director:
Post PhD Mara Mădălina Mihai
e-mail: mara-madalina.mihai@icub.unibuc.ro
drmaramihai@gmail.com
Project mentor:
Prof. Univ. Dr .Veronica Lazăr
e-mail: veronica.lazar2009@gmail.com
Main objective: The study consists in the investigation of the species diversity and virulence of the strains present into the bacterial consortium colonizing chronic venous leg ulcers and the consecutive host inflammatory response in order to identify prognostic biomarkers of wound healing, aiming towards a personalized and more efficient therapeutic approach.
To achieve the main objective, we have formulated the following specific objectives:
O 1: To set up the patients cohort with the enrollment in the study of a statistically significant number of patients diagnosed with chronic venous ulcers of the lower limbs, the collection of clinical data and the biological samples required for the optimal development of the scientific research activities.
O 2: To establish the microbiological profile (species composition and virulence features of the harvested strains) of chronic venous leg ulcers (using culture-dependent and -independent methods), in order to correlate this profile with the evolution of infection and the healing outcome.
O 3: To investigate the inflammatory host response to wound colonization, by the determination/ characterization of local markers (eg. cytokines, proteolytic activity of the wound fluid) and systemic markers (hematological, biochemical, serological), in order to correlate this profile with the evolution of infection and the healing outcome.
O 4: Project management and dissemination of the results.
Estimated results:
• Report on the clinical and anamnestic data of the patients included in the study.
• Characterization of the microbiological profile of chronic leg venous ulcers (bacterial species, virulence profile).
• Characterization of the inflammatory profile of the host, locally (chronic venius ulcers) and systemic.
• Report on the statistical analysis of the data, highlighting the correlations between the clinical characteristics, the microbiological profile, the inflammatory profile and the evolution of the ulcers.
• Highlighting potential prognostic markers of chronic venous ulcers.
• Dissemination of research results by publishing at least 3 journal articles indexed in the ISI-Web of Knowledge and at least 4 oral or poster-type communications in conferences.
Total value from budget: 249.999,99 RON/ 53.191,49 EUR
Total value of the contract: 1249.999,99 RON/ 53.191,49 EUR
Dissemination:
Publications
Articles published in journals ISI- Web of Knowledge:
- Miron A, Giurcaneanu C, Mihai MM, Beiu C, Voiculescu VM, Popescu MN, Soare E, Popa LG. Antimicrobial Biomaterials for Chronic Wound Care. Pharmaceutics 2023, 15(6), 1606, DOI 10.3390/pharmaceutics15061606, IF 2022=5.4 (Co-author)
- Mihai MM, Ion A, Giurcaneanu C, Nitipir C, Popa AM, Chifiriuc MC, Popa MI, Ricar J, Popa LG, Sarbu I, Lazar V. The Impact of Long-Term Antibiotic Therapy of Cutaneous Adverse Reactions to EGFR Inhibitors in Colorectal Cancer Patients. J. Clin. Med. 2021, 10(15), 3219; https://doi.org/10.3390/jcm10153219, IF 2020= 4.241 (First author)
- Popa LG, Giurcaneanu C, Mihai MM, Beiu C, Orzan OA, Negoita S, Burcea M, Turlea RI, Enachescu CI. The use of cadaveric skin allografts in the management of extensive wounds. Rom J Leg Med. 2021; 29(1):37-44. DOI:10.4323/rjlm.2021.37 WOS:000672698000006, IF 2020=0.363 (Corresponding author)
Articles published in journals indexed in international databases:
- Mihai MM, Ion A, Khadiri H, Merticariu M, Cucu CI. The challenging management of genitoperineal hidradenitis suppurativa. DermatoVenerol. (Buc.). 2022; 67(3):25-32. (First author).
- Mihai MM, Giurcaneanu C, Popa LG, Ghorfi A, Balaceanu B, Beiu C, Popescu MN, Ion A. Negative pressure wound therapy in the management of typical chronic lower limb ulcers. DermatoVenerol. (Buc.). 2020; 66(2): 33-42. (First author).
- Balaceanu B, Giurcaneanu C, Popa LG, Beiu C, Ion A, Mageriu V, Popescu MN, Gurau CD, Mihai MM. The outcomes of negative pressure therapy on bilateral plantar lesions due to systemic sclerosis. Case report. DermatoVenerol. (Buc.). 2020; 66(2): 13-17. (Last author).
Chapters in international books:
- Chapter 4. Nano-targeted Drug Delivery Approaches for Biofilm-Associated Infections, Mihai MM, Holban AM, Ion A, Balaceanu B, Gurau CD, Veronica Lazar, în ”Emerging Nanomaterials and Nano-Based Drug Delivery Approaches to Combat Antimicrobial Resistance”, seria ”Micro & Nano Technologies (MNT)”, 2022, pagini 97-138 Elsevier, Eds. Saravanan M, Barabadi H, Mostafavi E și Webster TJ (Autor principal- Prim autor).
Conference participation
- Mihai MM, Lazar V, Chifiriuc CM, Popa MI, Holban AM, Curutiu C, Marinescu F, Boglarka Ifrim AE, Ditu LM. „The Study of the Antimicrobial Activity of Essential Oils in the Management of Chronic Wound Infections”, 33rd EWMA Conference 3-5.05.2023, Milano, Italy (Oral presentation)
- Mihai MM, Giurcaneanu C, Popa LG, Balaceanu B, Ion A, Beiu C, Popescu MN, Lazar V „Healing of bilateral plantar ulcerations in a patient diagnosed with systemic scleroderma by the use of negative pressure therapy”, 33rd EWMA Conference 3-5.05.2023, Milano, Italy (Poster)
- Mihai MM. Negtaive pressure therapy of chronic skin ulcers. National Congress- „Quo Vadis” Dermato – venerologia? Punte peste timp, un nou început. 09-13.11.2022, Bucharest, Romania (Oral presentation)
- Bălăceanu B, Giurcăneanu C, Popa LG, Ion A, Ghorfi A, Mihai MM. The effects of negative pressure therapy on the bilateral ulcerations of the soles in a patient diagnosed with systemic scleroderma, Reziderma 2021, Online, 09-11.06.2021 (Oral presentation)- Awarded presentation at the conference.
- Ghorfi A, Gliga C, Giurcaneanu C, Ion A, Balaceanu B, Mihai MM. Negative pressure therapy of atypical benign ulcers. Reziderma 2021, Online, 09-11.06.2021 (Poster)
- Mihai MM, Lazar V, Giurcaneanu C, Ion A, Stoica C, Dascalu T, Balaceanu B. Multiple chronic skin ulcers- unusual complications of seborrheic keratosis electroresection and excessive hygiene in an old male patient. The 20th National Congress of Dermatology with International Participation, Online, 11-17.10.2021 (Poster)
- Mihai MM, Dascălu AT. Negative pressure therapy in the management of lower limb ulcers. The 19th National Congress of Dermatology with International Participation, Online, 14-18.10.2020 (Poster)
- Mihai MM, Lazăr V, Chifiriuc MC, Giurcăneanu C, Holban AM, Gheorghe I, Bleotu C, Popa MI. OP18 Study on the complex interplay between virulence and antibacterial resistance of Staphylococcus aureus isolates from chronic skin ulcers, 2020 Virtual Conference of the European Wound Management Association (EWMA), 17-18.11.2020, Online Meeting (Oral presentation). The Science Comitee EMWA Conference 2020 evaluated the best presentation of the competition and awarded First Time International Presenter Prize to the projector director Mara Mădălina Mihai.










