{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:24:34Z","timestamp":1777861474450,"version":"3.51.4"},"reference-count":25,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Diabetes mellitus (DM) is a major global health concern, with diabetes-related foot disease (DFD) representing one of its most severe complications, often resulting in chronic infection, osteomyelitis, and limb amputation. Conventional therapies frequently fail in refractory cases, necessitating novel adjunctive strategies. Ozone therapy (OT) possesses antimicrobial, immunomodulatory, and oxygen-enhancing properties, while negative pressure wound therapy (NPWT) facilitates granulation, exudate removal, and tissue perfusion. This study explored the combined efficacy of OT and NPWT in advanced DFD. Materials and Methods: An exploratory, retrospective, observational cohort study was conducted at a specialized wound care center in Gda\u0144sk, Poland, between 2019 and 2022. The study included 30 patients (n = 30) with refractory DFD involving both soft tissue and bone infection who had not responded to previous conventional treatment. The analyzed treatment approach consisted of surgical debridement, application of topical ozonated preparations, and (NPWT) with instillation of ozonated saline administered over a six-week period. Clinical outcomes included wound healing assessed using the Wagner classification and wound volume reduction, pain intensity measured using the Numeric Rating Scale (NRS), inflammatory biomarkers (C-reactive protein [CRP] and procalcitonin [PCT]), and microbiological characteristics of wound cultures. Statistical analyses were performed using the Wilcoxon signed-rank test and the chi-square test, and regression modeling was applied to identify potential predictors of therapeutic response. Statistical significance was defined as p &lt; 0.05. Results: By week six, 100% of ulcers improved to Wagner stage \u22641, with 26.7% achieving stage 0. Median wound volume decreased from 5.5 cm3 to 0 cm3 (p &lt; 0.001). Pain scores declined from 7.2 \u00b1 0.96 points to 0.2 \u00b1 0.5 points (p &lt; 0.001). CRP and PCT levels decreased significantly (p &lt; 0.001), and microbiological clearance was observed in all cases. Higher body mass index (BMI) was associated with poorer pain reduction. Conclusions: The combination of standard wound care with OT and NPWT was associated with clinically relevant improvements in wound healing, infection control, systemic inflammation, and pain reduction in patients with refractory DFD. Although limited by a non-controlled design and small cohort size, these findings support further randomized controlled trials to define the role of this combined approach in integrated diabetic foot care.<\/jats:p>","DOI":"10.3390\/medicina62050827","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:32:22Z","timestamp":1777469542000},"page":"827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Combined Use of Ozone and Negative Pressure Wound Therapy in the Management of Diabetes-Related Foot Disease: A Retrospective Exploratory Cohort Study"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0625-148X","authenticated-orcid":false,"given":"Izabella","family":"Ku\u017amiuk-Glembin","sequence":"first","affiliation":[{"name":"Department of Nephrology, Transplantology and Internal Diseases, Medical University of Gdansk, University Clinical Centre, 80-214 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Bia\u0142omyzy","sequence":"additional","affiliation":[{"name":"ETER-MED, Wound Care Clinic, Non-Public Healthcare Centre, 80-822 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micha\u0142","family":"Sadowski","sequence":"additional","affiliation":[{"name":"ETER-MED, Wound Care Clinic, Non-Public Healthcare Centre, 80-822 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bogdan","family":"Biedunkiewicz","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantology and Internal Diseases, Medical University of Gdansk, University Clinical Centre, 80-214 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5515-5072","authenticated-orcid":false,"given":"Leszek","family":"Tylicki","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantology and Internal Diseases, Medical University of Gdansk, University Clinical Centre, 80-214 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Niew\u0119g\u0142owski","sequence":"additional","affiliation":[{"name":"ETER-MED, Wound Care Clinic, Non-Public Healthcare Centre, 80-822 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/ndt\/gfaf177","article-title":"IDF Diabetes Atlas 11th edition 2025: Global prevalence and projections for 2050","volume":"41","author":"Duncan","year":"2025","journal-title":"Nephrol. 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