BACKGROUND: Ozone is often used as an additive therapy for skin conditions like infectious diseases, wound healing, diabetic foot, and pressure ulcers. The viability of the nasal skin has crucial importance in revision rhinoplasty cases. The study investigates the potential benefits of medical ozone therapy in healing the nasal skin in multiple-operated cases.
METHODS: The study retrospectively examined 523 revision rhinoplasty patients operated by the first author from January 2017 to January 2024. Patients consenting to ozone therapy received 3 major autohemotherapy sessions post-surgery. Patients were divided into 2 groups: those with compromised nasal skin (infection, poor vascular supply) and those with normal healing. Age, gender, smoking, diabetes, previous surgeries, grafting materials, and techniques were considered.
RESULTS: Of the 523 patients, 12 (2.3%) experienced major skin complications like infection and necrosis, while 511 (97.7%) had no or minor issues, such as discoloration. In total, 301 patients accepted and received ozone therapy. Of the patients without major complications, 299 (58.3%) received ozone therapy, while 212 (41.7%) did not. Among the 12 with major complications, two (16.7%) received ozone therapy, and the remaining 10 (83.3%) did not. Ozone therapy recipients showed statistically fewer skin problems (p<0.05). Costal cartilage as tip and septal extension graft was linked to skin issues (p<0.05). No major adverse effects from ozone therapy were noted.
CONCLUSIONS: Our findings indicate that ozone therapy may be a safe and potentially effective option for patients undergoing revision rhinoplasty, especially those with compromised nasal skin. It appears to aid in skin healing and regeneration, possibly through enhancing oxygen delivery and modulation of the immune response. Ozone therapy is a promising adjunct treatment for managing skin complications in revision rhinoplasty patients.
METHODS: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

OBJECTIVE: This study aimed to assess the effectiveness of ozone therapy in treating Diabetes-related Foot Ulcer (DFU) and its outcomes.
METHODS: A systematic search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and ProQuest databases for published studies evaluating the use of ozone as an adjunct treatment for DFU, from inception to December 21, 2022. The primary outcome measure was the change in wound size after the intervention compared to pretreatment. Secondary outcomes included time to complete ulcer healing, number of healed patients, adverse events, amputation rates, and hospital length of stay. Quantitative data synthesis for the meta-analysis was performed using a random-effects model and generic inverse variance method, while overall heterogeneity analysis was conducted using a fixed-effects model. Interstudy heterogeneity was assessed using the I2 index (<50%) and the Cochrane Q statistic test. Sensitivity analysis was performed using the leave-one-out method.
RESULTS: The meta-analysis included 11 studies comprising 960 patients with DFU. The results demonstrated a significant positive effect of ozone therapy on reducing foot ulcer size (Standardized Mean Difference (SMD): -25.84, 95% CI: -51.65 to -0.04, p = 0.05), shortening mean healing time (SMD: -38.59, 95% CI: -51.81 to -25.37, p < 0.001), decreasing hospital length of stay (SMD: -8.75, 95% CI: -14.81 to -2.69, p < 0.001), and reducing amputation rates (Relative Risk (RR): 0.46, 95% CI: 0.30-0.71, p < 0.001), compared to standard treatment.
CONCLUSIONS: This meta-analysis indicates that ozone therapy has additional benefits in expediting complete DFU healing, reducing the amputation rates, and decreasing hospital length of stay, though its effects do not differ from standard treatments for complete ulcer resolution. Further research is needed to address the heterogeneity among studies and to better understand the potential beneficial effects of ozone therapy.

Our hypothesis that controlled ozone applications interfere with the redox balance of a biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication) has been verified over the past two decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes and type 2 diabetes, and in the prevention of intoxications. Low-dose ozone acts as a redox bioregulator: the restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase in the antioxidant repair markers, here mainly shown as a glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, and relevant data are displayed, evaluated and comprehensively discussed: the repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone-treated groups and depending on the indication, the stress markers are simultaneously reduced, and the redox system regains its balance.

Acute lung injury (ALI) linked to sepsis has a high mortality rate, with limited treatment options available. In recent studies, medical ozone has shown promising results in alleviating inflammation and infection. Here, we aimed to evaluate the therapeutic potential of medical ozone in sepsis-induced ALI using a mouse model, measuring behavioral assessments, lung function, and blood flow. Western blot was used to quantify the levels of protein. In vitro, experiments on BMDM cells examine the impact of AMPK inhibitors and agonists on phagocytic activity. Results indicate that medical ozone can enhance the survival rate, ameliorate lung injury, and improve lung function and limb microcirculation in mice with ALI. Notably, it inhibits NETs formation, a crucial player in ALI development. Medical ozone also counteracts elevated TF, MMP-9, and IL-1β levels. In ALI mice, the effects of ozone are nullified and BMDMs exhibit impaired engulfment of NETs following Sr-a1 knockout. Under normal physiological conditions, the use of an AMPK antagonist produces similar effects to Sr-a1 knockout, significantly inhibiting the phagocytosis of NETs by BMDMs. On the contrary, AMPK agonists enhance this phagocytic process. In conclusion, medical ozone can alleviate sepsis-induced lung injury via the AMPK/SR-A1 pathway, thereby enhancing phagocytosis of NETs by macrophages.

Broad cellular components-initiated efficient chemical reactions that occur in malignant cells may contribute to exploring emerging strategies for cancer treatment. Herein, an ozonated oleogel (OG(O)) was developed to achieve cancer ozone therapy (O3-T) based on intracellular Criegee\'s reaction. By integrating the chemo-drug, the ozone-loaded oleogel (Dox@OG(O)) was prepared as a chemotherapeutic agent for local O3-T, associated with chemotherapy (CT)/radiotherapy (RT)/immunotherapy and wound healing. The in vitro results showed that, Dox@OG(O) could achieve high ozone loading efficiency and ensure its stability. This Oleogel-mediated O3-T could directly destroy tumor cells via intracellular Criegee\'s reaction occurred on cell membranes, as well as the effects of tumor microenvironment (TME) regulation by the generation of oxygen/reactive oxygen species (ROS) and depletion of glutathione (GSH). Meanwhile, under the stimulation of X-ray, an accelerated free radical\'s production was observed, further combined with the radio-sensitivity after TME regulation, an effective anti-tumor effect would be achieved. Further on, in vivo results demonstrated that the locally implanted Dox@OG(O) could effectively inhibit the growth of both primary and secondary tumors. Considering these results above, it will serve as inspiration for future studies investigating of O3-T, especially for postoperative skin diseases.

UNASSIGNED: A high risk diabetic foot ulcer is treated by ozone therapy and collagen powder. The goal of this study was to report a high risk case, treated by ozone therapy, and collagen powder. Ozone therapy and collagen powder can improve healing process of diabetic foot ulcers.
UNASSIGNED: This case report presents a successful nonsurgical outpatient approach for managing a high-risk diabetic foot ulcer with tendon exposure in an older adult with uncontrolled diabetes mellitus and severe heart failure. Due to the patient\'s comorbidities, surgical intervention was not an option, leading to the utilization of ozone therapy, collagen powder, and Phenytoin ointment. The significance of this case lies in the treatment of a high-risk foot ulcer through a nonsurgical approach, considering the patient\'s uncontrolled diabetes and severe heart failure. Diabetic foot ulcers (DFUs) are debilitating and life-threatening complications, often resulting in amputations, socio-psychological burdens, and lifestyle changes. Conventional treatment methods have shown limited success, necessitating the exploration of new and innovative approaches. The use of ozone therapy has emerged as a potential treatment, but its safety and efficacy in DFUs require further investigation. The positive outcomes observed in this case report suggest that ozone therapy may be a viable option for treating DFUs, and further studies are recommended to evaluate its effectiveness.

BACKGROUND: The study determined the damage caused by formaldehyde (FA) exposure in blood and liver samples using biochemical markers. Histopathological analysis was performed using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method and measurement of CD68 cell density. To what extent the antioxidant molecules thymoquinone (TQ) and ozone (O3) reversed the damage caused by FA exposure was investigated, both when used alone and combined.
METHODS: Fifty-six Sprague-Dawley male rats of eight to ten weeks of age were used in the experiment. The rats were divided into eight groups, with seven rats in each group: the untreated control group, the group treated with TQ (10 mg/kg/day), the group treated with O3 (150 μg/kg/day), the group treated with TQ+O3, the group exposed to FA (10 ppm 8 h/day), the group receiving FA+TQ, the group receiving FA+O3, and the group receiving FA+TQ+O3. Serum aspartate transaminase (AST), alanine transaminase (ALT), total antioxidant (TAS, U/mL), and total oxidant (TOS, nmol/mL) levels were analyzed. TAS and TOS levels, CD68 cell density, and apoptotic cells were determined in liver tissues.
RESULTS: FA exposure caused an increase in serum AST and ALT levels of (p<0.05) experimental animals, a decrease in TAS levels in serum (p=0.03) and liver (p>0.05) and an increase in TOS levels (p>0.05), TUNEL positivity (p<0.001), and CD68 cell density (p=0.004). Administration of TQ and O3 as antioxidants significantly reversed biochemical and histopathological alterations in the serum and liver.
CONCLUSIONS: TQ and ozone therapy suppressed oxidative stress caused by FA exposure and reversed the emerging histopathological deteriorations. Ozone therapy did not suppress the effects of TQ. Therefore, ozone therapy can be given as a supportive therapy along with the main therapeutic agents. We think TQ and ozone therapy may be useful to protect individuals exposed to FA.

Besides being scarce, the drugs available for treating cutaneous leishmaniasis have many adverse effects. Ozone is an option to enhance the standard treatment due to the wound-healing activity reported in the literature. In this study, we evaluated the efficiency of ozonated sunflower oil as an adjuvant in treating cutaneous lesions caused by Leishmania amazonensis. BALB/c mice were infected with L. amazonensis, and after the lesions appeared, they were treated in four different schedules using the drug treatment with meglumine antimoniate (Glucantime®), with or without ozonated oil. After thirty days of treatment, the lesions\' thickness and their parasitic burden, blood leukocytes, production of NO and cytokines from peritoneal macrophages and lymph node cells were analyzed. The group treated with ozonated oil plus meglumine antimoniate showed the best performance, improving the lesion significantly. The parasitic burden showed that ozonated oil enhanced the leishmanicidal activity of the treatment, eliminating the parasites in the lesion. Besides, a decrease in the TNF levels from peritoneal macrophages and blood leukocytes demonstrated an immunomodulatory action of ozone in the ozonated oil-treated animals compared to the untreated group. Thus, ozonated sunflower oil therapy has been shown as an adjuvant in treating Leishmania lesions since this treatment enhanced the leishmanicidal and wound healing effects of meglumine antimoniate.

OBJECTIVE: Medication-related osteonecrosis of the jaws has been reported to be associated with bisphosphonate and RANKL inhibitor medications. This prospective clinical study aimed to assess the outcomes of pre-operative ozone infiltration therapy in patients with established MRONJ.
METHODS: The treatment protocol for ozone applications were designed as 20 applications ozone infiltration therapy followed by surgical interventions of necrotic tissue debridement using piezoelectric surgery instruments. The evaluation of the results based on the clinical and radiologic specifications considering the necrotic lesion reduction and healing. The study included 31 lesions in 29 patients. The mean follow-up was 23.6 months.
RESULTS: 25 lesions out of 31 healed totally without any remissions. The outcomes were not affected by any variables such as gender, age, type of pharmacological treatment, lesion location, and MRONJ staging. The statistically significant results were found among the clinical condition of the patients (p = 0.01) and administration route of medications (p = 0.004). Healing was significantly less in patients that received intra-vascular administrations. Clinical conditions of the patients were divided as osteoporosis, oncologic, and arthritis. Significantly better results were obtained in osteoporosis patients. 38% of the population experienced spontaneous sequestration with signs of improvements and the surgical interventions were canceled. According to the results, total healing of MRONJ lesions was seen in 79% patients (81% lesions).
CONCLUSIONS: Ozone therapy and debridement with Piezoelectric surgery can be considered as a safe and beneficial adjunctive treatment alternative for osteonecrosis lesions in cases of established MRONJ.

The objective of this study is to evaluate the effectiveness and safety of ozone therapy (OT) in the treatment of knee osteoarthritis (KOA), which is the most common form of the disease. We analysed systematic reviews (SRs) of randomised controlled trials (RCTs) using the \"A MeaSurement Tool to Assess systematic Reviews\" (AMSTAR2) instrument to evaluate their quality. We developed a narrative synthesis report with eight SRs (15 RCTs/3,685 patients) to summarise the findings. The AMSTAR2 analysis indicated that all reviews had critically low confidence ratings. Statistically significant effects in pain reduction using OT compared to placebo groups were reported in three SRs. OT was shown to be comparable to other therapies in one SR and not superior in the other five. Six SRs highlighted the need for additional RCTs with improved methodological quality to confirm the efficacy of OT for KOA. SRs found fewer consistent effects for improving joint function. Regarding safety, seven SRs reported a low prevalence of minor adverse events linked with OT. Finally, this umbrella review highlights the beneficial effects and safety of OT in the treatment of KOA, particularly in pain control. The low methodological quality of RCTs and SRs limits the possibility of drawing conclusions on the effectiveness of the procedure in comparison to other therapies. Ensure adequate compliance with guidelines such as Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and AMSTAR2 has the ability to improve the quality of SRs in this area.