The ozone: a therapeutic mediator in MODIC processes.

MODIC changes of signal in lumbar MRI offered a new vision of the spine degenerations process. Several theories try to explain this phenomenom. After a critical apraisal and based on our own experience, we propose ozone intradiscal injection as an effective and safe treatment for disc degeneration disease.

Clinical and imaging selection criteria treating lumbar disc herniations by oxygen-ozone therapy, corticosteroid and local anaesthetic.

Radicular lumbar back pain is an important public health problem not already provided with a unequivocal treatment approach. Medical and physical therapies represent the first solution, however when these are not successful, the second therapeutic step is still controversial and mini-invasive treatment may play an important role. In these cases oxygen-ozone therapy has been proved to be a very safe and effective option that is widely used with different modalities. This paper, by reviewing oxygen-ozone therapy literature data, aims to propose an effective procedural technique and to clarify patient’s selection criteria; furthermore complications and follow-up management are also considered.

Use of medical ozone in fail back surgery syndrome: a systematic review.

The safety and efficacy of ozone injections in the spine for lumbar disc herniation has been proved in two systematic reviews with one metaanalysis. Many other papers with lower evidence level were published before encouraging its use for this pathology and other degenerative spinal diseases. Fail back surgery syndrome (FBSS) is a terrible situation with no clear treatment option presently. Some authors have dared to use ozone injections in these patients, based on its antiinflammatory action and its highly save portfolio. Due to the great disability and dramatic situation of FBSS patients, a systematic review is mandatory in order to clarify the potential role of ozone in this pathology.

The role and the effects of the ozone paravertebral injections, in lumbar disc herniation patients.

The results obtained from a group of patients suffering from discoradicular conflict syndrome treated with paravertebral oxygen-ozone injections were analyzed. From a total number of 8500 patients treated with ozone during the period 2002/2015, 880 patients underwent intradiscal injection and 7620 patients were treated with paravertebral ozone injections. This paper analyses a subgroup of 1850 patients (24.28% of the patients who were treated with paravertebral injections), including those patients who underwent the total 10-session treatment, complied with a 5-year follow-up and with the sample homogeneity parameters following a predictability therapeutic effectiveness (PET) index devised for such purpose (PET index O3) by us in 2009. The outcomes were assessed based on the VAS score and modified Mac Nab criteria. Definite results determined positive post-treatment outcomes considered excellent and good in 81% of the cases. Such effectiveness percentage resulted lower than the one achieved with the intradiscal injection technique (89%), and higher than the percentage seen in papers on the selective nerve root block technique.

The diamod tip.

This issue 5 is devoted to spine diseases that can be treated or improved by using medical ozone. Dr. Alberto Alexandre compiled during 2015 and 2016 a number of papers from experienced authors in order to prepare a monographic issue but found a lot of difficulty in publishing it. I offered him our Journal to publish these scientific works and he agreed. COVID-19 pandemic has produce a huge increase in publishing time for all journals but we finally have been able to produce this issue. Due to the delay in its publication, some papers have been published by their authors in other journals. We are hardly working in issue 6 that will be opened for different topics and we are preparing issue 7 that we expect to be a monographic on dental applications. All papers are welcomed!

Ozone as integrative and complementary support for pharmacological therapy.

Ozone is not nowadays used in a single medical branch, due to its immune and metabolic effects. This molecule is considered as a pro-drug which can induce at certain non-toxic doses a rearrangement of the biochemical pathways with the activation of a second messenger in a cascade with a multiple system action. Nonetheless, its difference from a drug consists in the fact that its action can’t be explained as a simple interaction between a molecule and a receptor, thus, it can’t be considered according to the classical pharmacological schemes and new concepts must be defined. Furthermore, ozone is able to activate Nfr2 protein. Our study reflects how the levels of Nrf2 in peripheral blood mononuclear cells were found to increase immediately after ozone exposure and when measured 30 minutes following reinfusion demonstrating that the oxidative stress was able to activate all the blood components. After a series of 3 systemic indirect endovenous applications, Nrf2 returned back to the basal level. At the end of the experiment the activities of superoxide dismutase and catalase were increased. This metabolic pathway is common to all cell lines. In light of the above, ozone could be very helpful as integrative and complementary support for pharmacological therapy modulating the oxidative stress component in many illnesses, elderly and rare diseases, according to not only a legal regulation but also a proper education and training of physicians.

Ozone therapy as complementary treatment for surgical infection: case report.

Background: Infection is a serious surgical complication that increases significantly morbidity and mortality rates as well as health care expenses. Bacterial ever-growing resistance to antibiotics makes the treatment of such events even more troublesome. Objective: Report on a surgical infection case treated with ozone as a complementary therapy. Methods and Materials: Female, 65 years old, submitted to a complex surgical procedure for adult kyphotic deformity correction that presented with early post-surgical infection. The patient was treated with revision surgery and antibiotics that improved the condition but were unable to delete the infection. Ozone, in its gaseous form, was injected subcutaneously and paravertebraly twice weekly for three weeks. Results: After 3 weeks of treatment the wound healed completely and repeated visits and blood exams up to one year after the surgery did not show recurrence of infection. Conclusions: Although not a definite indication on validity of ozone therapy for surgical infections, the results of this case report indicate a new way that merits to be explored.

“Not just herniated disc” back pain: Outcome of oxygen-ozone treatment in selected applications.

Low back pain and sciatica are highly debilitating conditions affecting all socioeconomic groups at an increasingly early age. They are caused by different often concomitant spinal disorders: disc or facet joint disease, spondylolisthesis (with or without listhesis), vertebral body and interapophyseal arthrosis, spinal stenosis, radicular and synovial cysts and, more rarely, infections and primary or metastatic cancer.Treatment of low back pain and/or sciatica requires an accurate diagnosis based on thorough history-taking and physical examination followed by appropriate imaging tests, namely computed tomography and/or magnetic resonance scans in addition to standard X-rays of the spine.In recent years, several reports have demonstrated the utility of oxygen-ozone therapy in reducing the size of herniated discs. The present study reports on the outcome of oxygen-ozone treatment in 416 patients with non-discogenic low back pain caused by degenerative disease of the posterior vertebral compartment (facet synovitis, Baastrup syndrome, spondylolysis and spondylolisthesis, facet degeneration).

Treatment of Degenerative Disc Disease associated with Modic changes, with ozone therapy. A new therapeutic proposal.

Introduction. Modic Changes (MCs) represent signal changes in the vertebral endplate and subchondral bone region visualized on T1 and T2 weighted magnetic resonance images (MRI). Three types of MCs It have been identified (Types 1 to 3). Modic changes are commonly associated with low-back pain (LBP). In the last few years scientific papers have shown that one of the causes of MCs (fundamentally, the MCs type 1) is the infection caused by an anaerobic bacterium of very low virulence: Propionibacterium acnes (P. acnes). This bacterium resides on the human skin, oral cavity, intestinal tract, and external ear canal as normal flora. As a consequence of tooth brushing and endodontic-therapy, could invade the blood stream leading to transient bacteremia. The authors propose a treatment which consists of Amoxicillin-clavulanate (500 mg/125 mg) three times a day, at 8-hour intervals, for 90 days/100 days. Objectives. Ozone therapy could be the gold standard therapy for MC1 because ozone is a powerful anti-microbial, anti-inflammatory and analgesic agent, which regulates oxidative stress, immune system and oxygen metabolism. Materials and Methods Patients with LBP lasting 6 months or more and MC1 confirmed by MRI of lumbar spine L3/L4 or L4/L5 or L5/S1 and who responded with 5 or more points on the VAS scale were treated with three intradiscal sessions of ozone therapy and ten paravertebral sessions. Results. Patients who were treated with ozone therapy according to our treatment proposal showed a substantial improvement on VAS comparing the beginning and the end of the treatment. They show a significant difference in pain, and general condition. However, these results were not reflected on ODI scale, neither on the MRI but we could notice certain improvements.

Systemic Ozone Therapy as a complementary treatment in Internal Medicine [abstract]

INTRODUCTION: Some data available in the literature and the common clinical experience of the physicians that use ozone therapy suggest that the treatment with systemic ozone is useful as supportive treatment in Internal Medicine. Nonetheless some criticism raise from the scientific community concerning the demonstration of the real effectiveness of this treatment. The criticism is based on the observation that the outcomes are often not clearly defined. Recently we published two studies in which the exercise capacity improved by systemic ozone both in patients with severe heart failure and in patients with COPD (Chronic Obstructive Pulmonary Disease). (1, 2) Most of the patients admitted in the departments of Internal Medicine can be considered complex according to the Italian multicenter study (COMPLIMED – FADOI 2013). In a study recently published by our group similar results have been observed.(3). In clinical practice the therapeutic approach is aimed to treat each single, specific, pathophysiological target but in complex diseases a new approach should be desirable with the aim to support the effectiveness of the specific treatments in order to improve the clinical outcomes. To achieve this objective both clinicians and people involved in clinical research should take in account the scientific concept of complexity. According to its’ definition a system can be defined as a complex system if it consist of many constituents interrelated which reciprocally interfere inducing a change of the equilibrium of the whole system. For this reasons the analysis of a complex system cannot be made by the evaluation of the single components but must be done by the evaluation of the global changes due to the interference of the different elements. It is well known that systemic administration of ozone induces changes in several physiological targets that contribute to obtain a re-modulation of the whole biological system. Therefore the systemic treatment with ozone could be considered of interest as a supportive treatment in internal medicine aimed to obtain a modulation of different pathophysiological targets in complex diseases. Based on these clinical and theoretical assumptions different systematic observations have been carried out in our department in order to answer to the following questions about the efficacy and the usefulness of systemic ozone therapy in internal medicine: 1) May complexity be measured in Internal Medicine? 2) Does supportive systemic ozone therapy improve the outcome of the treatment in complex patients? 3) May oxidative stress value predict the effect of systemic ozone therapy in complex patients? According to the scientific and epistemological definition of complexity Morin and Prigogine (1996) stated that a complex system cannot be understood merely by the evaluation of the single constituents. By analogy the ultimate causes of a complex problem are not merely the bare bones. In fact a complex problem cannot be resolved simply by splitting up it in single factors but requires the analysis of the interaction between the constituent factors and a comprehensive vision. In medical research and in clinical practice several factors must be considered in order to evaluate the complexity of a clinical condition: 1) the phenotype (the specific way to react to the pathogenic agent); 2) the specific pathophysiological changes due to the primary disease; 3) the biological and biochemical features; 4) the wear and the time course of the pathophysiological changes; 5) the possibility to remove the primary cause of the disease; 6) the associate pathologies MATERIAL and METHODS: As far as the measurement of complexity in medicine it concerns it is necessary to achieve at least three results: 1) to identify a multi-parametric function which could take in account the status variables involved; 2) to homogenize different pathological condition on the basis of the changes of the whole alteration of the system; 3) to evaluate the changes induced by treatments with multiple targets. According to these major premises a complexity score for clinical research has been built up by our group. It has been named Paideia Complexity Score (PCS). PCS is divided in four indexes: 1) Quality Of Life Index from the Standard Questionnaire SF-36; 2) Biological and Biochemical Index of Severity; 3) Therapeutical Impact Index; 4) Clinical Impression Index (C.I.). Each index is graded in a numeric scale from 0 to 15 points. The maximum value of the score is 60 and the severity is graded into three groups: Mild (0-20); Moderate (20-40) ; Severe (40-60). 135 patients consecutively admitted in our department have been evaluated by the Paideia Complexity Score (PCS). The admittance diagnosis was: Chronic Obstructive Pulmonary Disease (59 pts); Ischemic Heart Disease (34 pts);Sleep Apnea Syndrome (29 pts); Diabetes Mellitus (13 pts). PCS resulted Mild or Moderate in 65 patients and Severe in 70 cases. The result indicates that more or less half of the patients admitted in a department of Internal Medicine must be considered in terms of complexity. Effectiveness of Systemic Ozone Therapy in patients with moderate or severe complexity score (PCS) 70 pts with Severe PCS (> 40 ) were treated by Systemic Ozone Therapy added to the regular medical treatment in order to evaluate the changes in the complexity score (PCS). Systemic Ozone Therapy was performed according to the standard procedure: ozone administered in 100 ml of blood at a concentration ranging from 15 mcrg/mL to 25 mcrg/mL twice a week both during the hospitalization and after discharge from the hospital for six weeks. The changes in PCS were evaluated at the end of the treatment by a member of the medical staff unaware about the treatment with ozone (single blind). In 29 out of the 70 pts the PCS evaluated changed from severe to mild, in 7 patients a reduction from severe to moderate was recorded whereas 34 pts did not change the complexity score. 15 with PCS between 20 and 40 (moderate) who received the same schedule of treatment were also evaluated. In 13 pts the PCS changed from moderate to mild and in two pts no changes were recorded. No differences in terms of diagnosis and/or concomitant pathologies have been observed between the group of patients who improved the PCS and the group in which no changes were observed. Oxidative stress and effectiveness of Systemic Ozone Therapy BAP (biological antioxidant potential) test and dROMs (reactive oxygen metabolites) test are commonly used as the laboratory tests aimed to measure the degree of the oxidative stress in several clinical conditions. Nonetheless systematic studies in different clinical conditions are not yet available in literature and the clinical usefulness of these test remains still unclear. On the other hand, in clinical practice, it is commonly accepted that high plasma levels of reactive oxygen metabolites indicate the presence of a condition of exposure to endogenous or exogenous oxidants both in healthy subjects and in patients. In order to evaluate the usefulness of the measurement of the plasma levels of the reactive oxygen metabolites in predicting the effectiveness of Systemic Ozone Therapy we evaluated: 1)The relationship between dROMs Values and PCS (Paideia Complexity Score) in 55 patients by simple linear regression. 2)The changes in dROMs in 21 COPD patients treated with Systemic Ozone Therapy. 3)The per cent changes of dROMs and of SF – 36 Quality of Life index in 25 patients with severe PCS (Paideia Complexity Score). RESULTS: 1) The correlation coefficient (r) between dROMs and PCS resulted 34. Therefore no correlation has been demonstrated between the level of oxidative stress and the degree of complexity of the pathologies treated. 2) COPD patients treated with Systemic Ozone Therapy showed an improvement of the dROMs values in 14 out of the 21 patients (66%). 3) In 25 patients with severe PCS the treatment with Systemic Ozone Therapy induced a not significant decrease of 8% of the dROMs values whereas the Quality of Life SF – 36 increased of 40%. DISCUSSION: The systematic observation of patients admitted in our department of internal medicine indicate that roughly one half of cases must be considered characterized by the complexity. Therefore on theoretical basis the supportive treatment with Ozone should be considered useful. The use of an index of complexity allows to evaluate the effect of treatment with Systemic Ozone. According to the results obtained by the evaluation of the changes of the index of complexity the supportive treatment with ozone was effective in 58% of cases. No clinical and pathophysiological parameters have been identified to predict the effectiveness of the treatment. The evaluation of the oxidative stress do not correlate both with the degree of complexity of the disease and with the effectiveness of Systemic Ozone Therapy.