Clinical relevance of circulating angiogenic cells in patients with ischemic stroke.

BACKGROUND: Endothelial progenitor cells (EPCs) are circulating angiogenic cells with endothelial features associated with risk for stroke. We aimed to delve into their functional characteristics. EPCs were isolated and cultured from Ischemic Stroke (IS) patients and predictors of their variance evaluated. METHODS: This is a single-center observational study evaluating 187 consecutively hospitalized patients with IS. EPCs were isolated from blood samples. The number of circulating angiogenic cells (CACs), colony-forming units (CFU-ECs) and the emergence of late outgrowths endothelial cells (LOECs) were counted. We collected clinical variables and measured the stromal cell-derived factor 1 alpha (SDF1α) serum levels. We also examined the relative telomere length and the expression of osteogenic gene markers in CACs. RESULTS: CACs counts and CFU-ECs colony numbers were positively correlated (rho = 0.41, p < 0.001, n = 187). We found significant differences according to whether thrombolytic treatment was performed in the distribution of CFU-ECs (odds ratio (OR) = 2.5; 95% confidence interval (CI) 1.01-6.35; p = 0.042) and CACs (OR = 4.45; 95% IC 1.2-15.5; p = 0.012). The main determinants of CACs variation were the number of risks factors, thrombolysis treatment, arterial hypertension, LOECs occurrence, and the vascular endothelial growth factor expression, whereas CFU-ECs variations depended on hemoglobin content and the relative reduction in the National Institutes of Health Stroke Scale (NIHSS) criteria. The main predictors of LOECs appearance were thrombolysis and length of hospital stay. CONCLUSIONS: Our study supports the relevance of patient risk factors and treatments in the analysis of the functional properties of EPCs.

A Review of Genetic Polymorphisms and Susceptibilities to Complications after Aneurysmal Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) and vasospasm are two complications of subarachnoid hemorrhages (SAHs) which entail high risks of morbidity and mortality. However, it is unknown why only some patients who suffer SAHs will experience DCI and vasospasm. The purpose of this review is to describe the main genetic single nucleotide polymorphisms (SNPs) that have demonstrated a relationship with these complications. The SNP of the nitric oxide endothelial synthase (eNOS) has been related to the size and rupture of an aneurysm, as well as to DCI, vasospasm, and poor neurological outcome. The SNPs responsible for the asymmetric dimetilarginine and the high-mobility group box 1 have also been associated with DCI. An association between vasospasm and the SNPs of the eNOS, the haptoglobin, and the endothelin-1 receptor has been found. The SNPs of the angiotensin-converting enzyme have been related to DCI and poor neurological outcome. Studies on the SNPs of the Ryanodine Receptor yielded varying results regarding their association with vasospasm.

Persistence of SARS-CoV-2 infection on personal protective equipment (PPE).

BACKGROUND: SARS-CoV-2 stability and infection persistence has been studied on different surfaces, but scarce data exist related to personal protective equipment (PPE), moreover using realist viral loads for infection. Due to the importance for adequate PPE management to avoid risk of virus infection, RNA stability was evaluated on PPE. METHODS: Persistence of SARS-CoV-2 infection and detection of genomic RNA in PPE (gowns and face masks) were determined by in-vitro assays and RT-qPCR, respectively. Samples were infected with a clinical sample positive for SARS-CoV-2 (Clin-Inf), and with a heat-inactivated SARS-CoV-2 strain sample (Str-Inf) as a control. RESULTS: PPE samples infected with Clin-Inf were positive for the 3 viral genes on gowns up to 5 days post-infection, whereas these overall genes were detected up to 30 days in the case of face masks. However, gowns and FFP2 masks samples contaminated with Clin-Inf showed a cytopathic effect over VERO cells up to 5-7 days post-infection. CONCLUSIONS: SARS-CoV-2 RNA was detected on different PPE materials for 5 to 30 days, but PPE contaminated with the virus was infectious up to 5-7 days. These findings demonstrate the need to improve PPE management and to formulate strategies to introduce viricidal compounds in PPE fabrics.

Modulation by Ozone Therapy of Oxidative Stress in Chemotherapy-Induced Peripheral Neuropathy: The Background for a Randomized Clinical Trial.

(1) Background: Chemotherapy-induced peripheral neuropathy (CIPN) decreases the quality of life of patients and can lead to a dose reduction and/or the interruption of chemotherapy treatment, limiting its effectiveness. Potential pathophysiological mechanisms involved in the pathogenesis of CIPN include chronic oxidative stress and subsequent increase in free radicals and proinflammatory cytokines. Approaches for the treatment of CIPN are highly limited in their number and efficacy, although several antioxidant-based therapies have been tried. On the other hand, ozone therapy can induce an adaptive antioxidant and anti-inflammatory response, which could be potentially useful in the management of CIPN. (2) Methods: The aims of this works are: (a) to summarize the potential mechanisms that could induce CIPN by the most relevant drugs (platinum, taxanes, vinca alkaloids, and bortezomib), with particular focus on the role of oxidative stress; (b) to summarize the current situation of prophylactic and treatment approaches; (c) to describe the action mechanisms of ozone therapy to modify oxidative stress and inflammation with its potential repercussions for CIPN; (d) to describe related experimental and clinical reports with ozone therapy in chemo-induced neurologic symptoms and CIPN; and (e) to show the main details about an ongoing focused clinical trial. (3) Results: A wide background relating to the mechanisms of action and a small number of experimental and clinical reports suggest that ozone therapy could be useful to prevent or improve CIPN. (4) Conclusions: Currently, there are no clinically relevant approaches for the prevention and treatment of stablished CIPN. The potential role of ozone therapy in this syndrome merits further research. Randomized controlled trials are ongoing.

Pulsed Ultrasounds Reduce Pain and Disability, Increasing Rib Fracture Healing, in a Randomized Controlled Trial.

INTRODUCTION: Rib fractures are an important health issue worldwide, with significant, pain, morbidity, and disability for which only symptomatic treatment exists. OBJECTIVES: Based on our previous experimental model, the objective of the current study was to assess for the first time whether pulsed ultrasound (PUS) application could have beneficial effects on humans. METHODS: Prospective, double-blinded, randomized, controlled trial of 51 patients. Four were excluded, and 47 were randomized into the control group (N = 23) or PUS group (N = 24). The control group received a PUS procedure without emission, and the PUS group received 1 Mhz, 0.5 W/cm2 for 1 min/cm2. Pain level, bone callus healing rate, physical and work activity, pain medication intake, and adverse events were blindly evaluated at baseline and one, three, and six months. RESULTS: There were no significant differences at baseline between groups. PUS treatment significantly decreased pain by month 1 (P = 0.004), month 3 (P = 0.005), and month 6 (P = 0.025), significantly accelerated callus healing by month 1 (P = 0.013) and month 3 (P < 0.001), accelerated return to physical activity by month 3 (P = 0.036) and work activity (P = 0.001) by month 1, and considerably reduced pain medication intake by month 1 (P = 0.057) and month 3 (P = 0.017). No related adverse events were found in the PUS group. CONCLUSIONS: This study is the first evidence that PUS treatment is capable of improving rib fracture outcome, significantly accelerating bone callus healing, and decreasing pain, time off due to both physical activity and convalescence period, and pain medication intake. It is a safe, efficient, and low-cost therapy that may become a new treatment for patients with stable rib fractures.

Radiation therapy improves survival for unresectable postpneumonectomy lung tumors.

BACKGROUND: Additional resection for cancer in the single lung is often considered a prohibitive risk. The role of radiation therapy (RT) in this patient population is less clear with very limited available data. In this study, we sought to examine patients with postpneumonectomy lung cancer not amenable to surgery, identify factors associated with receiving RT, and determine the impact of RT on survival outcomes. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (1988-2013) was queried for patients with inoperable contralateral lung cancer after pneumonectomy. Univariate and multivariate analyses were performed to identify factors associated with the receipt of RT. Survival outcomes were examined using the Kaplan-Meier method. RESULTS: In total, 191 patients with inoperable postpneumonectomy lung cancer were included. RT was delivered to 122 (63.9%) patients; 69 (36.1%) patients did not receive RT. On multivariate analysis, disease stage was identified as the only predictor associated with receipt of RT (P < 0.001). The median overall survival (OS) and disease-specific survival (DSS) for patients receiving RT were higher than those for patients who did not receive RT (25 versus 8 mo and 29 versus 10 mo, respectively; P < 0.001). Similarly, patients who received RT had a higher 3-y OS (34% versus 14%, P < 0.001) than those who did not receive RT. On subset analysis, survival benefit with RT was observed in patients with all tumor size groups, and there was a trend toward superior survival in patients with stage I/II disease, who received RT compared with those who did not. On multivariate Cox regression analysis, RT use was independently associated with decreased hazards of death after adjusting for other factors (HR, 0.539; P < 0.001). CONCLUSIONS: Based on our analysis of the Surveillance, Epidemiology, and End Results (SEER) database, RT is associated with improved outcomes in inoperable patients with a contralateral lung cancer after pneumonectomy compared with observation alone.

Oncological resection of lung cancer invading the aortic arch In full thickness using a non-fenestrated endograft.

T4 lung cancer invading the full thickness of the aortic arch was completely removed in a 78-year-old lady using a non-fenestrated endograft closing the left subclavian artery origin without performing surgical revascularization. Left thoracotomy and upper lobectomy with resection of superior segment of the lower lobe and full thickness of the infiltrated aorta was performed without covering the aortic defect. The margins of the specimen were free of tumor. The patient survived 32 months. J. Surg. Oncol. 2016;114:412-415. © 2016 Wiley Periodicals, Inc.

Stem cells protect the bronchial stump in rat, increasing Sox6, Col2a1, and Agc1 expression.

BACKGROUND: Post-pneumonectomy bronchopleural fistulas (BPFs) are associated with high morbidity and mortality. Currently, since the management of BPFs is difficult to assess, the best therapeutic approach is prevention. Our objective was to evaluate the effects of adipose-derived stem cells (ASCs) on the healing of the bronchial stump in an experimental animal model. METHODS: Left pneumonectomy was performed in 37 Sprague-Dawley rats. Animals were randomly assigned to a control group (n = 13), an ASC group (n = 12), and an ASC plus Tissucol(®) group (ASCT) (n = 12). The ASCs and ASCTs were locally administered at the bronchial stump after surgical pneumonectomy. Animals were killed at 10 and 20 days. We analyzed histological changes and changes in the expression of relevant genes involved in wound repair in the bronchial stump. RESULTS: Two control animals, one animal from the ASC group, and one from the ASCT group died from early BPF. All the remaining animals had an adequate postoperative outcome. ASCs and ASCTs significantly decreased the necrosis and ulcerations of the bronchial stump at 10 and 20 days. ASCs significantly decreased mRNA expression of Igf1 at 10 days and Igf1, Tgfb1, Vegfa, and Col2a1 at 20 days, whereas there was increased expression of Agc1 and Col2a1 at 10 days and Sox6 at 20 days. CONCLUSIONS: Our findings indicate that local ASCs protected the bronchial stump after pneumonectomy and induced local changes in gene expression related to their protective action. These results could lead to a potential new therapeutic modality for the prevention of BPF.

Autologous platelet-poor plasma decreases the bronchial stump necrosis in rat.

BACKGROUND: Necrosis of the bronchial stump is a very important trigger for bronchopleural fistula. The administration of local autologous platelet-poor plasma (PPP) could protect the bronchial stump. MATERIALS AND METHODS: Left pneumonectomy was performed in 25 Sprague-Dawley rats. Animals were randomly assigned to a control group (n=13) and PPP group (n=12). PPP was locally administered on the bronchial stump after pneumonectomy. We analyzed histologic changes in the bronchial stump and messenger RNA expression changes of genes involved in wound repair at 10 and 20 d. RESULTS: Local PPP treatment produced a mass of fibrous tissue surrounding the bronchial stump and significantly decreased the presence of necrosis at 20 d. PPP increased the expression of insulin like growth factor 1 at 10 d although it did not reach statistical significance. CONCLUSIONS: Our findings indicate that local PPP treatment of the bronchial stump after pneumonectomy decreased necrosis and could have a protective effect on the bronchial stump.

An Artificial Intelligence Prediction Model of Insulin Sensitivity, Insulin Resistance, and Diabetes Using Genes Obtained through Differential Expression.

Insulin is a powerful pleiotropic hormone that affects processes such as cell growth, energy expenditure, and carbohydrate, lipid, and protein metabolism. The molecular mechanisms by which insulin regulates muscle metabolism and the underlying defects that cause insulin resistance have not been fully elucidated. This study aimed to perform a microarray data analysis to find differentially expressed genes. The analysis has been based on the data of a study deposited in Gene Expression Omnibus (GEO) with the identifier "GSE22309". The selected data contain samples from three types of patients after taking insulin treatment: patients with diabetes (DB), patients with insulin sensitivity (IS), and patients with insulin resistance (IR). Through an analysis of omics data, 20 genes were found to be differentially expressed (DEG) between the three possible comparisons obtained (DB vs. IS, DB vs. IR, and IS vs. IR); these data sets have been used to develop predictive models through machine learning (ML) techniques to classify patients with respect to the three categories mentioned previously. All the ML techniques present an accuracy superior to 80%, reaching almost 90% when unifying IR and DB categories.

Effects of ozone therapy on anxiety and depression in patients with refractory symptoms of severe diseases: a pilot study.

Background: Patients with refractory symptoms of severe diseases frequently experience anxiety, depression, and an altered health-related quality of life (HRQOL). Some publications have described the beneficial effect of ozone therapy on several symptoms of this kind of patient. The aim of this study was to preliminarily evaluate, in patients treated because of refractory symptoms of cancer treatment and advanced nononcologic diseases, if ozone therapy has an additional impact on self-reported anxiety and depression. Methods: Before and after ozone treatment, we assessed (i) anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS); (ii) the HRQOL (according to the EQ-5D-5L questionnaire), which includes a dimension on anxiety and depression and a visual analog scale (VAS) measuring self-perceived general health. Results: Before ozone therapy, 56% of patients were on anxiolytic and/or antidepressant treatment. Before and after ozone therapy, the anxiety and depression HADS subscales (i) significantly correlated with the anxiety/depression dimension of the EQ-5D-5L questionnaire and (ii) inversely correlated with the health status as measured by the VAS. After ozone therapy, we found a significant improvement in anxiety and depression measured by both the (i) HADS subscales and (ii) EQ-5D-5L questionnaire. Conclusion: The addition of ozone therapy for patients with refractory symptoms of cancer treatment and advanced chronic nononcologic diseases can decrease anxiety and depression severity levels. Additional, more focused studies are ongoing to provide the needed explanatory information for this finding.

Effects of Ozone Treatment on Health-Related Quality of Life and Toxicity Induced by Radiotherapy and Chemotherapy in Symptomatic Cancer Survivors.

(1) Background: The continuous improvement in cancer treatment has led to improvement in patients' survival and a subsequent increase in the number of cancer survivors living with adverse side effects of cancer treatments, sometimes with a high and adverse impact on their health-related quality of life (HRQOL). Side effects of cancer treatments are frequently associated with chronic status of oxidative stress, inflammation, and/or ischemia. The potential for ozone treatment to modulate those processes and improve some of those adverse effects has previously been described. The aim of this study was to evaluate the effect of ozone treatment on the HRQOL and grade of toxicity in symptomatic cancer survivors. (2) Methods: Before and after ozone treatment, we assessed (i) the HRQOL (according to the EQ-5D-5L questionnaire) and (ii) the grade of toxicity (according to the Common Terminology Criteria for Adverse Events of the National Cancer Institute of EEUU (CTCAE v.5.0)) in 26 cancer survivors with chronic side effects of radiotherapy and chemotherapy. (3) Results: There was a significant (p < 0.001) improvement in the EQ-5D-5L index as per the self-reported outcome evaluation of patients' health status. All the dimensions of the EQ-5D-5L questionnaire (mobility, self-care, activities, pain/discomfort, and anxiety/depression) and the self-evaluation of the health status using the visual analog scale were significantly improved (p < 0.05). The grade of toxicity was also significantly decreased (p < 0.001). (4) Conclusions: In cancer survivors with chronic side effects of cancer treatment, ozone treatment can improve the grade of toxicity and the HRQOL. These results merit additional research. Further studies are ongoing.

Hyperspectral imaging benchmark based on machine learning for intraoperative brain tumour detection.

Brain surgery is one of the most common and effective treatments for brain tumour. However, neurosurgeons face the challenge of determining the boundaries of the tumour to achieve maximum resection, while avoiding damage to normal tissue that may cause neurological sequelae to patients. Hyperspectral (HS) imaging (HSI) has shown remarkable results as a diagnostic tool for tumour detection in different medical applications. In this work, we demonstrate, with a robust k-fold cross-validation approach, that HSI combined with the proposed processing framework is a promising intraoperative tool for in-vivo identification and delineation of brain tumours, including both primary (high-grade and low-grade) and secondary tumours. Analysis of the in-vivo brain database, consisting of 61 HS images from 34 different patients, achieve a highest median macro F1-Score result of 70.2 ± 7.9% on the test set using both spectral and spatial information. Here, we provide a benchmark based on machine learning for further developments in the field of in-vivo brain tumour detection and delineation using hyperspectral imaging to be used as a real-time decision support tool during neurosurgical workflows.

Long-term improvement by ozone treatment in chronic pain secondary to chemotherapy-induced peripheral neuropathy: A preliminary report.

Background: Pain secondary to chemotherapy-induced peripheral neuropathy (CIPN) can limit the administration of chemotherapy, cancer-treatment outcomes, and the quality of life of patients. Oxidative stress and inflammation are some of the key mechanisms involved in CIPN. Successful treatments for CIPN are limited. This report shows our preliminary experience using ozone treatment as a modulator of oxidative stress in chronic pain secondary to CIPN. Methods: Ozone treatment, by rectal insufflation, was administered in seven patients suffering from pain secondary to grade II or III CIPN. Pain was assessed by the visual analog scale (VAS). Results: All patients, except one, showed clinically relevant pain improvement. Median pain score according to the VAS was 7 (range: 5-8) before ozone treatment, 4 (range: 2-6) at the end of ozone treatment (p = 0.004), 5.5 (range: 1.8-6.3) 3 months after the end of ozone treatment (p = 0.008), and 6 (range: 2.6-6.6) 6 months after the end of ozone treatment (p = 0.008). The toxicity grade, according to the Common Terminology Criteria for Adverse Events (CTCAE v.5.0), improved in half of the patients. Conclusion: This report shows that most patients obtained clinically relevant and long-lasting improvement in chronic pain secondary to CIPN after treatment with ozone. These observed effects merit further research and support our ongoing randomized clinical trial (NCT04299893).

Ozone Eliminates SARS-CoV-2 from Difficult-to-Clean Office Supplies and Clinical Equipment.

(1) Background: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to cause profound health, economic, and social problems worldwide. The management and disinfection of materials used daily in health centers and common working environments have prompted concerns about the control of coronavirus disease 2019 (COVID-19) infection risk. Ozone is a powerful oxidizing agent that has been widely used in disinfection processes for decades. The aim of this study was to assess the optimal conditions of ozone treatment for the elimination of heat-inactivated SARS-CoV-2 from office supplies (personal computer monitors, keyboards, and computer mice) and clinical equipment (continuous positive airway pressure tubes and personal protective equipment) that are difficult to clean. (2) Methods: The office supplies and clinical equipment were contaminated in an area of 1 cm2 with 1 × 104 viral units of a heat-inactivated SARS-CoV-2 strain, then treated with ozone using two different ozone devices: a specifically designed ozonation chamber (for low-medium ozone concentrations over large volumes) and a clinical ozone generator (for high ozone concentrations over small volumes). SARS-CoV-2 gene detection was carried out using quantitative real-time polymerase chain reaction (RT-qPCR). (3) Results: At high ozone concentrations over small surfaces, the ozone eliminated SARS-CoV-2 RNA in short time periods-i.e., 10 min (at 4000 ppm) or less. The optimum ozone concentration over large volumes was 90 ppm for 120 min in ambient conditions (24 °C and 60-75% relative humidity). (4) Conclusions: This study showed that the appropriate ozone concentration and exposure time eliminated heat-inactivated SARS-CoV-2 RNA from the surfaces of different widely used clinical and office supplies, decreasing their risk of transmission, and improving their reutilization. Ozone may provide an additional tool to control the spread of the COVID-19 pandemic.

Ozone treatment effectively eliminates SARS-CoV-2 from infected face masks.

The current COVID-19 pandemic is causing profound health, economic, and social problems worldwide. The global shortage of medical and personal protective equipment (PPE) in specialized centers during the outbreak demonstrated the need for efficient methods to disinfect and recycle them in times of emergency. We have previously described that high ozone concentrations destroyed viral RNA in an inactivated SARS-CoV-2 strain within a few minutes. However, the efficient ozone dosages for active SARS-CoV-2 are still unknown. The present study aimed to evaluate the systematic effects of ozone exposure on face masks from hospitalized patients infected with SARS-CoV-2. Face masks from COVID-19 patients were collected and treated with a clinical ozone generator at high ozone concentrations in small volumes for short periods. The study focused on SARS-CoV-2 gene detection (assessed by real-time quantitative polymerase chain reaction (RT-qPCR)) and on the virus inactivation by in vitro studies. We assessed the effects of different high ozone concentrations and exposure times on decontamination efficiency. We showed that high ozone concentrations (10,000, 2,000, and 4,000 ppm) and short exposure times (10, 10, and 2 minutes, respectively), inactivated both the original strain and the B.1.1.7 strain of SARS-CoV-2 from 24 contaminated face masks from COVID-19 patients. The validation results showed that the best condition for SARS-CoV-2 inactivation was a treatment of 4,000 ppm of ozone for 2 minutes. Further studies are in progress to advance the potential applications of these findings.

Estradiol worsens the syndrome of ischemia-reperfusion injury in an experimental lung transplantation model.

Ischemia-reperfusion injury (IRI) is a common complication after lung transplantation. There is evidence that reactive oxygen species are involved in its pathogenesis. We designed an experimental study to evaluate whether the administration of antioxidants to lung transplantation recipients protects against IRI and early acute rejection (AR). Twenty-five rats received left lung transplants after 6 h of ischemia. Fifty minutes before the reperfusion, groups of five rats received a single dose of desferrioxamine (20 mg/kg), estradiol (25 mg/kg), or melatonin (10 mg/kg). The animals were killed 48 h after surgery and the postoperative outcome, IRI, and AR were evaluated. The frequency of severe injury and of moderate-to-severe edema was higher in animals treated with estradiol than in the control group (P = 0.022 and P = 0.026, respectively). No significant changes in the degree of IRI or AR were observed in the groups treated with desferrioxamine or melatonin. In our study, treatment with the antioxidants melatonin or desferrioxamine before reperfusion had no effects on IRI damage or on AR frequency or severity. However, treatment with estradiol resulted in a worse postoperative outcome and in severe edema. Therefore, despite the antioxidant capacity of estradiol, it is recommended that an evaluation of these adverse effects of estradiol in human lung transplant recipients be performed.

Ozone potential to fight against SAR-COV-2 pandemic: facts and research needs.

The greatest challenge the world is facing today is to win the battle against COVID-19 pandemic as soon as possible. Until a vaccine is available, personal protection, social distancing, and disinfection are the main tools against SARS-CoV-2. Although it is quite infectious, the SARS-CoV-2 virus itself is an enveloped virus that is relatively fragile because its protective fatty layer is sensitive to heat, ultraviolet radiation, and certain chemicals. However, heat and liquid treatments can damage some materials, and ultraviolet light is not efficient in shaded areas, so other disinfection alternatives are required to allow safe re-utilization of materials and spaces. As of this writing, evidences are still accumulating for the use of ozone gas as a disinfectant for sanitary materials and ambient disinfection in indoor areas. This paper reviews the most relevant results of virus disinfection by the application of gaseous ozone. The review covers disinfection treatments of both air and surfaces carried out in different volumes, which varies from small boxes and controlled chambers to larger rooms, as a base to develop future ozone protocols against COVID-19. Published papers have been critically analyzed to evaluate trends in the required ozone dosages, as a function of relative humidity (RH), contact time, and viral strains. The data have been classified depending on the disinfection objective and the volume and type of the experimental set-up. Based on these data, conservative dosages and times to inactivate the SARS-CoV-2 are estimated. In small chambers, 10-20 mg ozone/m3 over 10 to 50 min can be sufficient to significantly reduce the virus load of personal protection equipment. In large rooms, 30 to 50 mg ozone/m3 would be required for treatments of 20-30 min. Maximum antiviral activity of ozone is achieved at high humidity, while the same ozone concentrations under low RH could result inefficient. At these ozone levels, safety protocols must be strictly followed. These data can be used for reducing significantly the viral load although for assuring a safe disinfection, the effective dosages under different conditions need to be confirmed with experimental data.

Ozone therapy versus surgery for lumbar disc herniation: A randomized double-blind controlled trial.

OBJECTIVES: Surgery is the treatment of choice for symptomatic disc herniation after conservative management. Several studies have suggested the potential utility of intradiscal ozone infiltration in this pathology. The aim of this trial was to compare intradiscal ozone infiltration vs. oxygen infiltration vs. surgery. DESIGN AND INTERVENTIONS: This was a randomized, double-blinded, and controlled trial in patients on a waiting list for herniated disc surgery. There were three treatment groups: surgery; intradiscal ozone infiltration (plus foraminal infiltration of ozone, steroids, and anesthetic); intradiscal oxygen infiltration (plus foraminal infiltration of oxygen, steroids, and anesthetic). MAIN OUTCOME MEASURES: The requirements for surgery. RESULTS: Five years after the treatment of the last recruited patient (median follow-up: 78 months), the requirement for further surgery was 20 % for patients in the ozone group and 60 % for patients in the oxygen group. 11 % of patients initially treated with surgery also required a second surgery. Compared to the surgery group, the ozone group showed: 1) significantly lower number of inpatient days: median 3 days (interquartile range: 3-3.5 days) vs. 0 days (interquartile range: 0-1.5 days), p = 0.012; 2) significantly lower costs: median EUR 3702 (interquartile range: EUR 3283-7630) vs. EUR 364 (interquartile range: EUR 364-2536), p = 0.029. CONCLUSIONS: Our truncated trial showed that intradiscal ozone infiltrations decreased the requirements for conventional surgery, resulting in decreased hospitalization durations and associated costs. These findings and their magnitude are of interest to patients and health services providers. Further validation is ongoing.