Medical Ozone as a Therapeutic Option in Musculoskeletal Pain Control: A Critical Review of Clinical Trials Considering Safety and Quality Indicators for Procedures and Devices.

Background: Drug therapies have been widely applied for pain management, however, there are important side effects such as those related to corticosteroids and opioids. Recent studies demonstrated promising results using medical ozone as a safe, effective, and low-cost intervention for pain control. Objective: to review and critically analyze clinical studies that used ozone therapy for musculoskeletal pain. Methods: a literature search of various databases was performed to identify relevant studies. From a total of 249 records, 27 studies were included. Quality indicators, human and device factors that strongly influence the generation of evidence were considered, such as study design and device safety. We also mitigated biases, considering the safety and efficacy of the intervention itself. Results: Regarding safety, 77 (8%) of studies reported no adverse effects; concerning efficacy outcomes, medical ozone shows to be an effective intervention on musculoskeletal pain control. Important information about used devices were missing. Conclusions: medical ozone shows to be safe and effective; qualification of health professionals as well as the device safety are mandatory. However, there is a lack of requirements to identify the best therapeutic scheme; further longer, clinical and rigorous trials are needed.

The efficacy of ultrasonography-guided oxygen-ozone therapy versus corticosteroids in patients with knee osteoarthritis: A multicenter randomized controlled trial.

BACKGROUND: Osteoarthritis (OA) is a widely-known disease distinguished by the breakdown of joint cartilage, leading to pain and morning stiffness. In this context, the role of corticosteroids is well known, but there is still a gap of knowledge on the duty of oxygen-ozone therapy (O2-O3). OBJECTIVE: To evaluate for effectiveness of ultrasound-guided O2-O3 injections compared with corticosteroid injections among patients diagnosed with knee OA. METHODS: This randomized controlled clinical trial was conducted on participants with knee OA who were randomly sorted into two groups: group A, undergoing corticosteroid group (n= 47) and group B, undergoing O2-O3 (n= 49) were injected within the knee joint under ultrasound guidance. The primary outcome measure was the change in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score between baseline and 12-weeks post-injection. Secondary outcome measures included visual analog scale scores, joint effusion and a knee flexion ROM. Assessments were recorded at baseline and 4-weeks and 12-weeks post-injection. For the examination of intra- and inter-group variations at various time points, a repeated-measure analysis of variance (two-way ANOVA) was employed. RESULTS: Ninety-six participants completed this study. Based on repeated measurement analysis of variance, a significant effect of time was found for all outcome measures in both groups. Both groups showed clinically significant improvements in knee pain, quality of life and, function. Baseline, 4-week post-injection and 12-week post-injection WOMAC scores (mean ± standard deviation) were 72.54 ± 18.89, 45,95 ± 13.30 and 37.10 ± 19.87 (p= 0.00, p= 0.00, p= 0.00; respectively) in the corticosteroid group, respectively and 68.23 ± 20.18, 42.99 ± 18.67, and 33.43 ± 18.24 (p= 0.00, p= 0.00, p= 0.00; respectively) in the ozone group, respectively. However, no significant group × time interaction was determined regarding all outcome measures. CONCLUSION: The study demonstrates the efficacy of O2-O3 compared to steroid injections regarding functioning and pain relief among patients with diagnosed knee OA.

Efficacy of ozone therapy for oral mucosa wound healing: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis to assess the effectiveness of ozone therapy in oral ulcers healing when compared to placebo or active treatments. MATERIALS AND METHODS: The search was carried out using PubMed, EMBASE, Scopus, and Lilacs databases. Clinical trials involving human participants were included. The Risk Ratio (RR) and the standardized mean difference (SMD) with 95%CI (confidence interval) were calculated. The ROBINS-I (risk of bias in non-randomized studies of interventions) and RoB2 (risk of bias tool for randomized trials) assessment tool was used to detect bias. RESULTS: After the selection process, 12 studies were included. The meta-analysis showed that ozone therapy helps to reduce the size of the traumatic and autoimmune ulcers (RR=-0.44; 95% CI -0.71,-0.17; I2=0%) in comparison to placebo. Regarding pain reduction, ozone was superior to placebo (RR = 1.29, 95% CI -1.6 to -0.95); I2=0%), and equivalent to topical corticosteroid and laser photobiomodulation (RR = 0.26, 95% CI -0.27,0.78, p = 0.34). CONCLUSION: Ozone therapy is an alternative for accelerating healing and reducing pain for both traumatic and autoimmune ulcers. However, the quality of evidence is limited. CLINICAL RELEVANCE: Oral ulcerations are usually painful and impact quality of life requiring different approaches to boost wound healing and reduce symptoms. For this purpose, ozone therapy is a promising strategy.

[Prospects for the use of ozone therapy and low-intensity laser therapy in the treatment of atrophic pharyngitis]. / Perspektivy primeneniya ozonoterapii i nizkointensivnoi lazeroterapii pri lechenii atroficheskogo faringita.

Chronic pharyngitis (CP) is one of the most common diseases of the oropharynx. The number of referrals from patients with CP reaches 70% of the total number of referrals to an otorhinolaryngologist. The development of this disease is facilitated by the neuro-reflex factor and a violation of trophic and metabolic processes. It should be noted that of all forms of CP, the greatest impact on the quality of life is noted precisely in atrophic pharyngitis (AP), due to the presence of pronounced subjective sensations from the oropharynx. Many of the modern methods of treatment do not provide a lasting effect due only to the application, superficial local effect on the altered mucous membrane of the posterior pharyngeal wall, without taking into account the changes caused by a violation of trophic processes in the tissue. A promising direction in the treatment of atrophic pharyngitis is the use of a combined technique - ozone therapy and low-intensity laser therapy. The article presents the results of the application of fine-drip irrigation of the mucous membrane of the posterior pharyngeal wall with Ozonide oil in combination with low-intensity laser radiation on the projection of vessels supplying blood to the middle parts of the oropharynx. OBJECTIVE: Improving the effectiveness of treatment of patients with atrophic pharyngitis through the use of ozone therapy and low-intensity laser therapy. MATERIAL AND METHODS: A single-center experimental controlled randomized open-label study of 90 patients with AP aged 18 and over was conducted. All patients were randomly divided into three groups depending on the treatment performed: group I - traditional treatment method (rinsing the oropharynx with antiseptic solutions, the use of tablets for resorption), group II - treatment with ozone therapy (fine drip irrigation of the mucous membrane of the posterior pharyngeal wall with Ozonide oil), group III - treatment with ozone therapy and laser therapy. During the examination of patients, anamnesis collection, examination of ENT organs, cytological and microbiological examination of the mucous membrane of the posterior pharyngeal wall, contact endoscopy of the mucous membrane of the posterior pharyngeal wall were performed. 5-point visual analogue scales (VAS) were used to assess complaints and pharyngoscopic signs. RESULTS: Our results showed a statistically significant improvement in the quality of life of patients with AP (p=0.012), an improvement in the pharyngoscopic picture (p=0.003). The results obtained by us indicate an improvement in microcirculation under the influence of ozone therapy and low-intensity laser radiation. The technique using ozone therapy and low-intensity laser therapy is characterized by a bactericidal and fungicidal effect. There is a decrease in the total contamination of the posterior wall of the oropharynx with pathogenic and saprophytic microflora (there is a decrease in the contamination of the posterior wall of the pharynx with saprophytic and pathogenic microflora (p≤0.05), the differences are statistically significant). The technique using ozone therapy and low-intensity laser therapy has a pronounced anti-inflammatory effect, which was expressed in a decrease in the severity of dyskeratosis and hyperkeratosis. Thus, the use of ozone therapy in combination with laser therapy opens up new prospects for pathogenetically sound and effective treatment of AP.

The Management of Necrotizing Gingivitis in Paediatric Patients: A Scoping Review and Two Case Reports.

Necrotizing gingivitis (NG) is an acute inflammatory process with an estimated prevalence of less than 1%. The treatment of choice is usually antibiotics in addition to periodontal treatment. This scoping review aims to detail extent and type of proof related to NG in paediatric patient; moreover, a decision tree protocol was developed to define NG management in paediatric patients based on the presence or absence of systemic compromission. In addition, we also propose the use of ozone treatment as an adjuvant therapy. Seven papers (3 case reports, 2 guidelines, and 2 reviews) were selected for evaluation by reading the full texts. This review outlines the lack of research on the treatment of NG in paediatric patients; we, however, demonstrate the efficacy of the decision tree protocol by describing two case reports in which patients were treated with antibiotics according to the presence or absence of systemic involvement through the implementation of an individualized therapeutic approach, with periodontal ozone therapy. Moreover, the supportive use of this molecule in the management of NG can be a valuable tool in the healing of gingival tissues.

Cognitive, Neuropsychological and Biological Effects of Oxygen-Ozone Therapy on Frailty: A Study Protocol for a 5-Week, Randomized, Placebo-Controlled Trial.

Cognitive frailty (CF) is a heterogeneous syndrome that is becoming one of the most serious health problems as the world's population age is increasing. Elucidating its biological mechanisms as well as prevention and treatments is becoming increasingly significant, particularly in view of the associated health costs. We presented the study protocol of a research project funded by the Italian Ministry of Health (grant number RF-2016-02363298) aiming to investigate the cognitive and neuropsychological effects of a 5-week treatment with therapy based on the regenerative properties of ozone (O3) in a cohort of subjects stratified according to CF scores. We also studied the potential effects of O3 on blood-based biomarkers indicative of specific biological systems that may be altered in CF. Seventy-five older persons were recruited and randomly assigned to receive the active treatment (150 cc of oxygen-O2-O3 mixture at the concentration of 30 µg of O3 per cc of O2), O2, or the placebo (air) for 5 weeks. The main endpoints were the change in the scores of clinical scales from baseline (T0) to weeks 3 (T3), 9 (T9), and 15 (T15) after treatment and the change in biomarker levels resulting from transcriptomics, proteomics, and metabolomic patterns at the same times. The positive results from this study could have important clinical implications.

Systemic Ozone Therapy May Improve the Perception of Quality of Life: Ozonized Glucose Solution 5% Extends Reach to Patients Ineligible for Blood Infusion.

Ozone therapy is a complementary treatment that has gained popularity due to its safety and wide range of applications. Systemic ozone therapy involves withdrawing 100 to 200 ml of blood, treating it with an oxygen-ozone mixture, and then reinfusing it. This process requires large-caliber venous access, which can be a limitation. To overcome this, alternative administration methods have been explored, including the use of ozonized solutions. The aim of this study is to evaluate the clinical effects of systemic ozone therapy on the perception of quality of life and to analyze the outcomes of different administration methods. Three groups of patients were treated: one group received classical systemic ozone therapy, another received ozone therapy via intravenous infusion of a 5% glucose solution, and the third group alternated between the two methods. The results showed an improvement in perceived quality of life in all groups, regardless of the method used. Thus, systemic ozone therapy showed efficacy in improving the perception of quality of life in our group. Moreover, intravenous infusion of a 5% glucose solution has made it possible to treat patients who could not be treated with the classical method, achieving similar results.

Effect of Medical Ozone Therapy in Preventing Compromised Nasal Skin in Revision Rhinoplasty.

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. LEVEL OF EVIDENCE IV: 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 .

Effect of Ozone Therapy on Diabetes-related Foot Ulcer Outcomes: A Systematic Review and Meta-analysis.

PURPOSE: 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. CONCLUSION: 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.

Successful treatment of severe and recurrent hand eczema with infection in human immunodeficiency virus patients: A case report.

Hand eczema is a common allergic disease characterized by a chronic relapsing course with a 15% lifetime prevalence. Human immunodeficiency virus-infected individuals have a higher risk of Staphylococcus aureus infection which is associated with the severity of hand eczema. Incidences of allergic diseases including hand eczema and chronic itch are higher in patients with human immunodeficiency virus. Pruritus is one of the most common symptoms in hand eczema, sometimes intractable pruritus provokes repeated scratching, picking, disfigurement, and can even worsen the lesion. Currently, there is no ideal treatment for hand eczema, the treatment of hand eczema in human immunodeficiency virus patients is even more difficult. Here, we present a case of recurrent and therapy-resistant hand eczema patients combined with Staphylococcus aureus infection, human immunodeficiency virus infection was better improved by being treated with topical ozone therapy.

In Vitro and In Vivo Effects of Melatonin-Containing Combinations in Human Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis and high mortality rates. Therefore, it is necessary to identify new targets and therapeutic strategies to improve the prognosis of patients with PDAC. Integrative therapies are increasingly being used to boost the efficacy of the known anticancer therapeutic approaches. Hence, this study aimed to evaluate the effects of a novel combination of different potential anticancer molecules, melatonin (MLT), cannabidiol (CBD), and oxygen-ozone (O2/O3) to treat PDAC using in vitro and in vivo models of human PDAC. The effect of this combination was investigated in combination with gemcitabine (GEM), the most common chemotherapeutic drug used for PDAC treatment. The combination of MLT + CBD + O2/O3 was more effective than the individual treatments in inhibiting PDAC cell viability and proliferation, inducing cell death, and modulating the RAS pathway protein levels. Moreover, different combinations of treatments reduced tumor mass in the PDAC mouse model, thus promoting the effect of GEM. In conclusion, a mixture of MLT + CBD + O2/O3 could serve as a potential adjuvant therapeutic strategy for PDAC.

A pilot randomized controlled trial of major ozone autohemotherapy for patients with post-acute sequelae of COVID-19.

This prospective, randomized, controlled clinical trial assessed the therapeutic effects of major ozone autohemotherapy (O3-MAH) in patients with post-acute sequelae of COVID-19 (PASC). Seventy-three eligible participants were randomly assigned to an O3-MAH plus conventional therapy group (n = 35) or a conventional therapy alone group (n = 38). Symptom score, pulmonary function, 6-minute walk distance (6MWD), and hematological, biochemical, and immunological parameters were evaluated before and after the interventions. Both groups demonstrated improvements in various parameters post-intervention, but efficacy was greater in the O3-MAH group than the conventional treatment group; with intervention effectiveness defined as a ≥ 50 % reduction in symptom score, 25 of 35 patients (71 %) responded to O3-MAH, while 17/38 patients (45 %) responded to conventional treatment alone (P = 0.0325). Significant improvements in symptom scores (P = 0.0478), tidal volume (P = 0.0374), predicted 6MWD (P = 0.0032), and coagulation and inflammatory indicators were noted in the O3-MAH group compared with the conventional treatment group. O3-MAH was more likely to be effective in patients with elevated CRP levels. Furthermore, O3-MAH markedly improved cellular immunity, and this improvement became more pronounced with extended treatment duration. In summary, combining O3-MAH with conventional treatment was more effective than conventional therapy alone in improving symptoms, pulmonary function, inflammation, coagulation, and cellular immunity in patients with PASC. Further research is now warranted to validate these findings and individualize the regimen.

Mitochondrial Dysfunction, Its Oxidative Stress-Induced Pathologies and Redox Bioregulation through Low-Dose Medical Ozone: A Systematic Review.

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.

Medical ozone alleviates acute lung injury by enhancing phagocytosis targeting NETs via AMPK/SR-A1 axis.

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-1ß 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.

Intracellular Criegee's mechanism-based synergistic ozone therapy mediated by oleogels for cancer treatment.

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.

Successful treatment of a high-risk diabetic foot ulcer by ozone therapy and collagen powder: A case report.

Key Clinical Message: 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. Abstract: 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.

Oxygen-ozone therapy for pain relief in patients with trapeziometacarpal osteoarthritis: a proof-of-concept study.

PURPOSE: Trapeziometacarpal osteoarthritis (TMC-OA) is a prevalent hand disorder affecting a growing number of people worldwide. While a multidisciplinary approach might provide additional advantages, the analgesic and anti-inflammatory role of intra-articular oxygen-ozone (O2O3) injections combined with physical therapy is still unknown. To assess the impact of a multimodal therapeutic approach combining O2O3 injections with physical therapy in patients with TMC-OA. MATERIALS AND METHODS: A prospective open-label study conducted in the Physical and Rehabilitation Medicine Unit of the "Renato Dulbecco" University Hospital of Catanzaro. We assessed patients with TMC-OA who had not responded to standard medical therapy. Participants received O2O3 therapy and targeted physical therapy for 4 weeks. Pain relief, muscle strength, and physical functioning were assessed at baseline and after 4, 12 and 24 weeks (respectively T0, T1, T2, and T3). RESULTS: Seventeen patients with a mean age of 67.1 ± 6.1 years were included in the study. Short-term improvements in pain intensity were observed (T0: 6.221 ± 1.514; T1: 3.172 ± 1.1451; p < .001) and were maintained over a 24-week follow-up period (T0: 6.221 ± 1.514; T3: 4.393 ± 1.438; p: 0.006). Significant changes were reported also in terms of muscle strength and physical functioning. O2O3 therapy was well-tolerated with no adverse effects. CONCLUSIONS: A combination of O2O3 injections and physical therapy might be considered in patients with TMC-OA. Further investigation is warranted to assess the effectiveness of O2O3 therapy in managing TMC-OA.

The addition of intra-articular trapeziometacarpal O₂O₃ injections to physical therapy is safe and reliable for thumb osteoarthritisO₂O₃ injection could be considered a second-line mini-invasive approach option when simple analgesic and non-pharmacologic interventions have failed, and surgical treatment is not yet indicatedO₂O₃ injections in combination with physical therapy may provide benefits in terms of pain relief in patients with TMC joint OA in whom previous conventional medical therapy has been unsuccessful.

Efficacy and safety of ozone therapy for knee osteoarthritis: an umbrella review of systematic reviews.

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.

Ozone infiltration as an adjunctive treatment to piezoelectric surgery in the management of medication-related osteonecrosis of the jaws: case series of 29 patients.

PURPOSE: 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). CONCLUSION: 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.

Use of Ozone Therapy and Thymoquinone in the Prevention of Formaldehyde Toxicity by Inhalation: An Experimental Study.

INTRODUCTION: 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. CONCLUSION: 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.