Use of oxygen-ozone therapy to improve the effectiveness of antibiotic treatment on infected arthroplasty: protocol for a superiority, open-label, multicentre, randomised, parallel trial.

INTRODUCTION: Surgical site infections still remain a major public health challenge and have become an increasing universal risk, especially for the implantation of orthopaedic devices.Unfortunately, the discovery and increasingly widespread use (especially the misuse) of antibiotics have led to the rapid appearance of antibiotic-resistant strains today; more and more infections are caused by microorganisms that fail to respond to conventional treatments.Oxygen-ozone therapy has been extensively used and studied for decades across various potential medical applications and has provided consistent effects with minimal side effects.This study aims to determine the superiority of oxygen-ozone therapy in combination with oral antibiotic therapy in patients with wound infections after an orthopaedic device implantation when compared with antibiotic therapy alone. METHODS AND ANALYSIS: This is an open-label, multicentre, randomised, parallel-group study that aims to assess the efficacy and safety of oxygen-ozone therapy in combination with oral antibiotic therapy to treat infections in patients (male or female aged ≥18 years) having undergone surgery for the implant of an orthopaedic device. Patients must have at least one (but no more than three) postoperative wounds in the site of surgery (ulcers, eschars and sores) and at least one symptom (pain, burning, redness and malodour) and at least one sign (erythema, local warmth, swelling and purulent secretion) of infection of at least moderate intensity (score ≥2) in the target lesion at the screening visit (patients with wounds without signs of localised infection or with undermining wounds will be excluded).Patients (n=186) will be recruited from five Italian hospitals and studied for 7 weeks. All will be assigned to one of the two treatment groups according to a web-based, centralised randomisation procedure and placed into either the (1) intervention: oxygen-ozone therapy 2-3 times a week for 6 weeks (for a maximum of 15 sessions) simultaneously with an appropriate oral antibiotic therapy prescribed at baseline or (2) control: oral antibiotic therapy prescribed at baseline.The primary outcome is the efficacy and superiority of the treatment (ozone and oral antibiotic therapies); secondary outcomes include the resolution of signs and symptoms, modifications in lesion size and the treatment's safety and tolerability. ETHICS AND DISSEMINATION: This study has been reviewed and approved by the responsible Independent Ethics Committee (IEC) of COMITATO ETICO CAMPANIA NORD, located at 'Azienda Ospedaliera San Giuseppe Moscati di Avellino'.After completion of the study, the project coordinator will prepare a draft manuscript containing the final results of the study on the basis of the statistical analysis. The manuscript will be derived by the co-authors for comments, and after revision, it will be sent to a major scientific journal. Findings will be disseminated via online and print media, events and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04787575.

The Oxygen-Ozone Adjunct Medical Treatment According to the Protocols from the Italian Scientific Society of Oxygen-Ozone Therapy: How Ozone Applications in the Blood Can Influence Clinical Therapy Success via the Modulation of Cell Biology and Immunity.

BACKGROUND: Ozone is an allotrope of oxygen whose use in medicine has rapidly grown in recent years. Ozonated blood allows for the use of ozone in a safe modality, as plasma and blood cells are endowed with an antioxidant system able to quench ozone's pro-oxidant property and to elicit the Nrf2/Kwap1/ARE pathway. METHODS: We present two clinical studies, a case-series (six patients) observational study adopting ozone as a major autohemotherapy and topical ozone to address infected post-surgical wounds with multi-drug resistant bacteria and an observational study (250 patients) using ozonated blood for treating knee osteoarthritis. RESULTS: Ozonated blood via major autohemotherapy reduced the extent of infections in wounds, reduced the inflammatory biomarkers by more than 75% and improved patients' QoL, whereas ozonated blood via minor autohemotherapy improved significantly (p < 0.001) WOMAC and Lequesne's parameters in knee osteoarthritis. CONCLUSIONS: The models described, i.e., ozone autohemotherapy in wound antimicrobial treatment and ozonated blood in knee osteoarthrosis, following our protocols, share the outstanding ability of ozone to modulate the innate immune response and address bacterial clearance as well as inflammation and pain.

Cytokine profiles in COVID-19 patients undergoing adjunct ozone therapy: some comments.

A comment to: Ghaleh HEG, Izadi M, Javanbakht M, Ghanei M, Einollahi B, Jafari NJ, Alishiri G, Aslani J, Abolghasemi H, Simonetti V, Khafaei M, Zhao S, Saadat SH, Ahmadi M, Parvin S, Vazifedoust S, Alvanagh AG. Cytokine profile and antioxidants status in the moderate and severe COVID-19 patients: a trial of ozone therapy impact as a medicinal supplement. Inflammopharmacology. 2023 Jul 12. https://doi.org/10.1007/s10787 -023-01288-9.

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Greatly Improved Fatigue Symptoms When Treated with Oxygen-Ozone Autohemotherapy.

(1) Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic syndrome characterized by fatigue as its major and most outstanding symptom. Previous evidence has supported the ability of ozone to relief ME/CFS related fatigue in affected patients (2) Methods: A number of 200 ME/CFS previously diagnosed patients, (mean age 33 ± 13 SD years) were consecutively treated with oxygen-ozone autohemotherapy (O2-O3-AHT). Fatigue was evaluated via an FSS 7-scoring questionnaire before and following 30 days after treatment. (3) Results: Almost half (43.5%) of the treated patients evolved their FSS scale from the worst (7) to the best (1) score, assessing the highest improvement from being treated with O2-O3-AHT. Furthermore 77.5% of patients experienced significant ameliorations of fatigue, of 4-6 delta score. No patient showed side effects, yet experienced long lasting fatigue disappearance, by three months follow up (4) Conclusions: Treatment with O2-O3-AHT greatly improves ME/CFS related fatigue, aside from sex and age distribution.

Male vs. Female Differences in Responding to Oxygen-Ozone Autohemotherapy (O2-O3-AHT) in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

(1) Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a syndrome that has fatigue as its major symptom. Evidence suggests that ozone is able to relieve ME/CFS-related fatigue in affected patients. (2) Objective: To evaluate whether differences exist between males and females in ozone therapy outputs in ME/CFS. (3) Methods: In total, 200 patients previously diagnosed with ME/CFS (mean age 33 ± 13 SD years) underwent treatment with oxygen-ozone autohemotherapy (O2-O3-AHT). Fatigue was investigated via an FSS 7-scoring questionnaire before and following 1 month after treatment. (4) Results: The Mann-Whitney test (MW test) assessed the significance of this difference (H = 13.8041, p = 0.0002), and female patients showed better outcomes than males. This difference was particularly striking in the youngest age cohort (14-29 years), and a KW test resulted in H = 7.1609, p = 0.007 for the Δ = 28.3% (males = 3.8, females = 5.3). (5) Conclusions: When treated with O2-O3-AHT, females respond better than males.

Oxygen-ozone (O2-O3) immunoceutical therapy for patients with COVID-19. Preliminary evidence reported.

OBJECTIVE: This study evaluated the potential efficacy of a novel approach to treat COVID-19 patients, using an oxygen-ozone (O2-O3) mixture, via a process called Oxygen-Ozone- Immunoceutical Therapy. The methodology met the criteria of a novel, promising approach to treat successfully elderly COVID-19 patients, particularly when hospitalized in intensive care units (ICUs) Experimental design: We investigated the therapeutic effect of 4 cycles of O2-O3 in 50 hospitalized COVID-19 subjects suffering from acute respiratory disease syndrome (ARDS), aged more than 60 years, all males and undergoing non invasive mechanical ventilation in ICUs. RESULTS: Following O2-O3 treatment a significant improvement in inflammation and oxygenation indexes occurred rapidly and within the first 9 days after the treatment, despite the expected 14-20 days. A significant reduction of inflammatory and thromboembolic markers (CRP, IL-6, D-dimer) was observed. Furthermore, amelioration in the major respiratory indexes, such as respiratory and gas exchange markers (SatO2%, PaO2/FiO2 ratio), was reported. CONCLUSION: Our results show that O2-O3 treatment would be a promising therapy for COVID-19 patients. It leads patients to a fast recovery from ARDS via the improvement of major respiratory indexes and blood gas parameters, following a relatively short time of dispensed forced ventilation (about one to two weeks). This study may encourage the scientific community to further investigate and evaluate the proposed method for the treatment of COVID-19 patients.

Corrigendum to "Association of Ozone with 5-Fluorouracil and Cisplatin in Regulation of Human Colon Cancer Cell Viability: In Vitro Anti-Inflammatory Properties of Ozone in Colon Cancer Cells Exposed to Lipopolysaccharides".

[This corrects the article DOI: 10.1155/2017/7414083.].

Cerebrovascular pattern improved by ozone autohemotherapy: an entropy-based study on multiple sclerosis patients.

Ozone major autohemotherapy is effective in reducing the symptoms of multiple sclerosis (MS) patients, but its effects on brain are still not clear. In this work, we have monitored the changes in the cerebrovascular pattern of MS patients and normal subjects during major ozone autohemotherapy by using near-infrared spectroscopy (NIRS) as functional and vascular technique. NIRS signals are analyzed using a combination of time, time-frequency analysis and nonlinear analysis of intrinsic mode function signals obtained from empirical mode decomposition technique. Our results show that there is an improvement in the cerebrovascular pattern of all subjects indicated by increasing the entropy of the NIRS signals. Hence, we can conclude that the ozone therapy increases the brain metabolism and helps to recover from the lower activity levels which is predominant in MS patients.

Association of Ozone with 5-Fluorouracil and Cisplatin in Regulation of Human Colon Cancer Cell Viability: In Vitro Anti-Inflammatory Properties of Ozone in Colon Cancer Cells Exposed to Lipopolysaccharides.

INTRODUCTION: Ozone therapy is an effective medical treatment for different diseases like mucositis, psoriasis, acute pain, neurovascular diseases, and cancer. The aim of this study is based on the association of different ozone concentration with 5-fluorouracil and cisplatin in human colon cancer cell (HT29 cell line) in order to investigate possible anticancer synergistic effects. METHODS: HT29 cells were incubated with ozone at different concentration ranging from 10 up to 50 µg/ml at different incubation time alone or in combination with cisplatin and 5-fluorouracil. Cell viability was performed by using a modified MTT method. Anti-inflammatory studies were conducted incubating HT29 with or without 20, 30, or 50 µg/ml of ozone before exposure to lipopolysaccharides. RESULTS: Ozone alone has a time and concentration dependent cytotoxicity against HT29 cells (IC50 at 24 h: 30 µg/ml). Association of ozone with drugs increases cytotoxicity by 15-20%. Preincubation of ozone at 50 µg/ml decreases IL-8, IL-6, and IL-1ß production by 50, 56, and 70%, respectively, compared to untreated cells. CONCLUSION: These results indicated that ozone could be useful in colon cancer management in combination with 5-fluorouracil and cisplatin with significant inhibition of cytokines having a central role in colon cancer cell survival and chemoresistance.

[Ozone therapy: a potential adjunct approach to lower urinary tract infection? A case series report]. / Ozone Therapy: Un potenziale approccio alla infezioni delle basse vie urinarie? A Case Series Report.

Multi-resistant drug bacteria are an emerging health care concern around the world. A decreased resistance to infection as seen in Chronic Kidney Disease (CKD) and kidney transplanted patients as well as some metabolic abnormalities such as hyperglycemia and glycosuria or clinical conditions such as the neurogenic bladder may indeed portend a great risk of recurrent urinary tract infections (UTI). The common and indiscriminate use of antibiotics often provides the patients with only a transient or partial amelioration of the urinary tract discomforts and increases the risk of multi-resistant drug bacteria selection. Thus a great effort is made in order to develop new antibacterial approaches especially in the setting of multi- antibiotic resistant pathogens. We herein report on some promising yet preliminary results of the use of ozone therapy in UTI.

Intramuscular oxygen-ozone therapy in the treatment of acute back pain with lumbar disc herniation: a multicenter, randomized, double-blind, clinical trial of active and simulated lumbar paravertebral injection.

STUDY DESIGN: Multicenter randomized, double-blind, simulated therapy-controlled trial in a cohort of patients with acute low back pain (LBP) due to lumbar disc herniation (LDH). OBJECTIVE: To assess the benefit of intramuscular-paravertebral injections of an oxygen-ozone (O2O3) mixture. SUMMARY OF BACKGROUND DATA: Recent findings have shown that O2O3 therapy can be used to treat LDH that fails to respond to conservative management. However, these findings are based on intradiscal/intraforaminal O2O3 injection, whereas intramuscular-paravertebral injection is the technique used most in clinical practice in Italy and other Western countries. METHODS: Sixty patients suffering from acute LBP caused by LDH was randomized to an intramuscular O2O3 or control group. Patients were observed up to assess pain intensity, LBP-related disability, and drug intake (15 [V2] and 30 [V3] days after treatment started, and 2 weeks [V4], and 3 [V5] and 6 [V6] months after treatment ended). RESULTS: A significant difference between the 2 groups in the percentage of cases who had become pain-free (61% vs. 33%, P < 0.05) was observed at V6. Patients who received O2O3 had a lower mean pain score than patients who received simulated therapy throughout the observation period. A significant improvement was observed in LBP-related disability in the study group patients when compared with the control group patients. Active O2O3 therapy was followed by a significantly lower number of days on nonsteroidal anti-inflammatory drugs at V2 and V3 and by a lower number of days at V4. No adverse events were reported. CONCLUSION: Treatment of LBP and sciatica is a major concern. Although the natural history of acute LBP is often self-limiting, conservative therapies are not always effective; in such cases, O2O3 intramuscular lumbar paravertebral injections, which are minimally invasive, seem to safely and effectively relieve pain, as well as reduce both disability and the intake of analgesic drugs.