Increased serum levels of proNGF, mature NGF and interleukins in burn-injured children.

OBJECTIVE: Burns are among the most common injuries in children. In burns of more than 20% of the total body surface area, a systemic inflammatory response involving several chemical mediators occurs. Among them, nerve growth factor (NGF) regulates the inflammatory response related to wound healing and promotes keratinocyte proliferation and angiogenesis. The aim of our study was to investigate the physiological response to injury in children with moderate-severe burns, assaying proNGF, mature NGF (mNGF), interleukins (IL)-1ß, and Il-10 serum levels. PATIENTS AND METHODS: This is a prospective observational study, including twelve children hospitalized for moderate-severe burns at the Gemelli Hospital (Rome). Their laboratory features were compared to those of patients with obstructive hydrocephalus who underwent surgery. RESULTS: Our results showed an increase in proNGF and mNGF serum levels. In burn patients, proNGF levels increased before mNGF, and serum concentrations of both were not correlated with burn extension and depth. The most significant levels of mNGF and proNGF were reported in scalds involving the face. Serum IL-1ß and IL-10 peak levels were reached with a time-course pattern similar to proNGF. CONCLUSIONS: Our preliminary results validate the hypothesis that serum levels of proNGF and mNGF may represent inflammatory biomarkers useful for monitoring burn patients and defining new strategies for their treatment.

Is there any correlation between otitis media and dental malocclusion in children? A systematic review.

PURPOSE: This study aims to evaluate whether there is a correlation between otitis and dental malocclusions. METHODS: Electronic databases were searched for observational studies published until July 2021 without language or time restrictions. PROSPERO: CRD42021270760. Observational studies on children with and without OM and/or malocclusion were included. After removing duplicates and excluding not-eligible articles, two reviewers screened relevant articles independently. Two reviewers independently extracted data and assessed data quality and validity through the Newcastle-Ottawa Scale (NOS) quality assessment tool for non-randomized studies. RESULTS: Five studies met the selection inclusion criteria and were included in the studies for a total of 499 patients. Three studies investigated the relationship between malocclusion and otitis media, while the remaining two studies analyzed the inverse relationship and one of them considered eustachian tube dysfunction as a proxy of OM. An association between malocclusion and otitis media and vice versa emerged, although with relevant limitations. CONCLUSION: There is some evidence that there is an association between otitis and malocclusion; however, it is not yet possible to establish a definitive correlation.

Management of late-onset fetal growth restriction: pragmatic approach.

OBJECTIVES: There is limited prospective evidence to guide the management of late-onset fetal growth restriction (FGR) and its differentiation from small-for-gestational age. The aim of this study was to assess prospectively a novel protocol in which ultrasound criteria were used to classify women with suspected late FGR into two groups: those at low risk, who were managed expectantly until the anticipated date of delivery, and those at high risk, who were delivered soon after 37 weeks of gestation. We also compared the outcome of this prospective cohort with that of a historical cohort of women presenting similarly with suspected late FGR, in order to evaluate the impact of the new protocol. METHODS: This was a prospective study of women with a non-anomalous singleton pregnancy at ≥ 32 weeks' gestation attending a tertiary hospital in London, UK, between February 2018 and September 2019, with estimated fetal weight (EFW) ≤ 10th centile, or EFW > 10th centile in addition to a decrease in fetal abdominal circumference of ≥ 50 centiles compared with a previous scan, umbilical artery Doppler pulsatility index > 95th centile or cerebroplacental ratio < 5th centile. Women were classified as low or high risk based on ultrasound and Doppler criteria. Women in the low-risk group were delivered by 41 weeks of gestation, unless they subsequently met high-risk criteria, whereas women in the high-risk group (EFW < 3rd centile, umbilical artery Doppler pulsatility index > 95th centile or EFW between 3rd and 10th centiles (inclusive) with abdominal circumference drop or abnormal Dopplers) were delivered at or soon after 37 weeks. The primary outcome was adverse neonatal outcome and included hypothermia, hypoglycemia, neonatal unit admission, jaundice requiring treatment, suspected infection, feeding difficulties, 1-min Apgar score < 7, hospital readmission and any severe adverse neonatal outcome (perinatal death, resuscitation using inotropes or mechanical ventilation, 5-min Apgar score < 7, metabolic acidosis, sepsis, and cerebral, cardiac or respiratory morbidity). Secondary outcomes were adverse maternal outcome (operative delivery for abnormal fetal heart rate) and severe adverse neonatal outcome. Women managed according to the new protocol were compared with a historical cohort of 323 women delivered prior to the implementation of the new protocol, for whom management was guided by individual clinician expertise. RESULTS: Over 18 months, 321 women were recruited to the prospective cohort, of whom 156 were classified as low risk and 165 were high risk. Adverse neonatal outcome was significantly less common in the low-risk compared with the high-risk group (45% vs 58%; adjusted odds ratio (aOR), 0.6 (95% CI, 0.4-0.9); P = 0.022). There was no significant difference in the rate of adverse maternal outcome (18% vs 24%; aOR, 0.7 (95% CI, 0.4-1.2); P = 0.142) or severe adverse neonatal outcome (3.8% vs 8.5%; aOR, 0.5 (95% CI, 0.2-1.3); P = 0.153) between the low- and high-risk groups. Compared with women in the historical cohort classified retrospectively as low risk, low-risk women managed under the new protocol had a lower rate of adverse neonatal outcome (45% vs 58%; aOR, 0.6 (95% CI, 0.4-0.9); P = 0.026). CONCLUSIONS: Appropriate risk stratification to guide management of late FGR was associated with a reduced rate of adverse neonatal outcome in low-risk pregnancies. In clinical practice, a policy of expectantly managing women with a low-risk late-onset FGR pregnancy at term could improve neonatal and long-term development. Randomized controlled trials are needed to assess the effect of an evidence-based conservative management protocol for late FGR on perinatal morbidity and mortality and long-term neurodevelopment. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Relationship between sex and clinical and imaging features of early axial spondyloarthritis: results from a 48 month follow-up (Italian arm of the SPondyloArthritis Caught Early (SPACE) study).

OBJECTIVES: To assess the association between sex and clinical and disease activity indices, and X-rays and magnetic resonance imaging (MRI) features, in early-stage axial spondyloarthritis (axSpA). METHOD: Baseline data analysis was conducted on the Italian SPACE cohort, including patients with chronic back pain (duration ≥ 3 months and ≤ 2 years; onset < 45 years). Patients underwent MRI and X-rays of the sacroiliac joints (SIJs) to establish the diagnosis of axSpA, according to Assessment of SpondyloArthritis international Society criteria and physician's judgement. Clinical features, disease activity and functional indices, and images were collected at baseline and yearly during 48 months. Spinal and SIJ X-rays and MRI images were scored by two readers following Spondyloarthritis Research Consortium of Canada (SPARCC), modified Stoke Ankylosing Spondylitis Spinal Score, and modified New York criteria. Characteristics of axSpA patients according to sex (male/female) were compared over time using descriptive statistics. RESULTS: Ninety-one patients had axSpA (83.5% non-radiographic; 16.5% radiographic); 47.3% were male. Males were younger, with shorter duration of axial symptoms, and more frequently had HLA-B27 positivity, radiographic sacroiliitis with a bilateral/symmetric pattern, and more signs of spondylitis. Females more frequently showed peripheral/entheseal involvement and the non-radiographic phenotype. Males showed increased pelvic/spinal radiographic progression and more often had active sacroiliitis on MRI. Although the frequency of inflammatory corner lesions did not differ between males and females, localization varied, with more cervical/thoracic MRI-spine lesions in females and more lumbar lesions in males. We observed a significant downward trend of SPARCC SIJ/spine scores in all patients, irrespective of sex. More fat lesions were observed on MRI-spine in females and on MRI-SIJ in males. CONCLUSION: Sex was associated with distinct axSpA features: females showed low-grade radiographic sacroiliitis and spinal progression, and a higher prevalence of cervical and thoracic spine MRI signs.

Comparative bench study evaluation of a modified snorkeling mask used during COVID-19 pandemic and standard interfaces for non-invasive ventilation.

PURPOSE: The aim of this bench study is to compare the standard NIV and nCPAP devices (Helmet, H; Full face mask, FFM) with a modified full face snorkeling mask used during COVID-19 pandemic. METHODS: A mannequin was connected to an active lung simulator. The inspiratory and expiratory variations in airways pressure observed with a high simulated effort, were determined relative to the preset CPAP level. NIV was applied in Pressure Support Mode at two simulated respiratory rates and two cycling-off flow thresholds. During the bench study, we measured the variables defining patient-ventilator interaction and performance. RESULTS: During nCPAP, the tested interfaces did not show significant differences in terms of ∆Pawi and ∆Pawe. During NIV, the snorkeling mask demonstrated a better patient-ventilator interaction compared to FFM, as shown by significantly shorter Pressurization Time and Expiratory Trigger Delay (p < 0.01), but no significant differences were found in terms of Inspiratory Trigger Delay and Time of Synchrony between the interfaces tested. At RR 20sim, the snorkeling mask presented the lower ΔPtrigger (p < 0.01), moreover during all the conditions tested the snorkeling mask showed the longer Pressure Time Product at 200, 300, and 500 ms compared to FFM (p < 0.01). A major limitation of snorkeling mask is that during NIV with this interface it is possible to reach maximum 18 cmH2O of peak inspiratory pressure. CONCLUSIONS: The modified snorkeling mask can be used as an acceptable alternative to other interfaces for both nCPAP and NIV in emergencies.

Tumor and peritumoral adipose tissue crosstalk: De-differentiated adipocytes influence spread of colon carcinoma cells.

Colorectal cancer is the second leading cause of cancer and often has a fatal course. There are many studies in the literature that have described a close functional relationship between the tumor mass and surrounding tissue, or tumor stroma, which is affected by the continuous metabolic exchange that occurs at the interface between tumor and tissues in contact with it. There is much evidence that the presence of adipose tissue in stroma plays a fundamental role in modulating the tumor microenvironment and promote tumor development, growth, and angiogenesis due to its endocrine characteristics. In this analysis, we have studied the alterations of adipose tissue surrounding colorectal tumors with MRI and optical imaging in vivo techniques to monitor tumor progression and also performed histological and molecular analysis. We detected differences in the principal adipose markers expressed by adipocytes residing around the rectal colon and observed that peritumoral adipose tissue is exposed to a mesenchymal transition process that leads to the acquisition of a less differentiated phenotype of adipocyte that represents the main cellular type present in tumor stroma. The mesenchymal transition correlated with the acquisition of more aggressive tumor phenotype and could represent a valid target for tumor therapy.

Subclinical TRAPS treated with canakinumab.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autoinflammatory disease characterized by recurrent episodes of fever and systemic inflammation. We describe the case of a 19-year-old patient who was referred to our attention with frequent subclinical TRAPS episodes characterized by mild arthralgias and crampy abdominal pain, without fever. Inflammatory markers, including serum amyloid A which increases the risk of long-term amyloidosis, were persistently high also when the patient was in good general conditions. Therapy with human anti-interleukin 1ß monoclonal antibody, canakinumab, led to disease control and normalization of the inflammatory markers, which are currently still normal. This clinical case supports the need to treat also subclinical TRAPS. In this respect, canakinumab is effective and reduces the risk of developing amyloidosis.

HMGB-1 and TGFß-1 highlight immuno-inflammatory and fibrotic processes before proteinuria onset in pediatric patients with Alport syndrome.

INTRODUCTION: Alport syndrome (ALP) is a rare genetic condition characterized by progressive involvement of the basal membranes and renal dysfunction. The purpose of the study was to evaluate urinary (u) and serum (s) levels of tumor growth factor (TGF)-beta(ß) and high mobility group box (HMGB)-1 in ALP patients with normal renal function, albuminuria and proteinuria. METHODS: A prospective, single-center study was performed with a follow-up period of 12 months, enrolling 11 pediatric ALP patients and 10 healthy subjects (HS). Normal values of serum creatinine, albuminuria and proteinuria, as well as unaltered estimated glomerular filtration rate (eGFR) were required at enrollment. RESULTS: ALP patients had significantly higher levels of serum and urinary HMGB1 compared to HS. The same trend was observed for TGF-ß1, with higher values in ALP patients than in HS. HMGB1 and TGF-ß1 correlated with each other and with markers of renal function and damage. Urinary biomarkers did not correlate with eGFR, whereas sHMGB1 and sTGF-ß1 were negatively related to filtration rate (r: - 0.66; p = 0.02, r: - 0.96; p < 0.0001, respectively). Using proteinuria as a dependent variable in a multiple regression model, only the association with sTGF-ß1 (ß = 0.91, p < 0.0001) remained significant. CONCLUSIONS: High levels of HMGB1 and TGF-ß1 characterized ALP patients with normal renal function, highlighting the subclinical pro-fibrotic and inflammatory mechanisms triggered before the onset of proteinuria. Further studies are needed to evaluate the role of HMGB1 and TGFß-1 in ALP patients.

Widening the Neuroimaging Features of Adenosine Deaminase 2 Deficiency.

Adenosine deaminase 2 deficiency (OMIM #615688) is an autosomal recessive disorder characterized by a wide clinical spectrum, including small- and medium-sized vessel vasculopathies, but data focusing on the associated neuroimaging features are still scarce in the literature. Here, we describe the clinical neuroimaging features of 12 patients with genetically proven adenosine deaminase 2 deficiency (6 males; median age at disease onset, 1.3 years; median age at genetic diagnosis, 15.5 years). Our findings expand the neuroimaging phenotype of this condition demonstrating, in addition to multiple, recurrent brain lacunar ischemic and/or hemorrhagic strokes, spinal infarcts, and intracranial aneurysms, also cerebral microbleeds and a peculiar, likely inflammatory, perivascular tissue in the basal and peripontine cisterns. Together with early clinical onset, positive family history, inflammatory flares and systemic abnormalities, these findings should raise the suspicion of adenosine deaminase 2 deficiency, thus prompting genetic evaluation and institution of tumor necrosis factor inhibitors, with a potential great impact on neurologic outcome.

Life-threatening complications of streptococcal sepsis: a PICU contemporary series.

BACKGROUND: Life-threatening streptococcal sepsis nowadays represents an uncommon event in previously healthy infants and children. Critically ill patients suffering from severe streptococcal sepsis complications may present with pre-antibiotic era clinical pictures and require a timely clinical approach to achieve restitutio ad integrum. RESULTS: We report a series of four patient groups affected by an uncommon life-threatening streptococcal sepsis, each of them exhibiting some distinct features. Streptococcus Agalactiae sepsis was associated with cerebral thrombotic/ischaemic lesions, whereas severe cardiogenic shock was prominent in the Streptococcus Viridans group; Streptococcus Faecalis and ß-hemolytic group A Streptococcus patients mostly reported lung complications. CONCLUSIONS: Previous antibiotic treatments should not delay aggressive treatment in the intensive care setting. Early diagnostic suspicion, as well as appropriate and aggressive treatment provided within an intensive care setting are crucial for the clinical outcome.

Water quality and human health: A simple monitoring model of toxic cyanobacteria growth in highly variable Mediterranean hot dry environments.

Due to population growth, urbanization and economic development, demand for freshwater in urban areas is increasing throughout Europe. At the same time, climate change, eutrophication and pollution are affecting the availability of water supplies. Sicily, a big island in southern Italy, suffers from an increasing drought and consequently water shortage. In the last decades, in Sicilian freshwater reservoirs several Microcystis aeruginosa and more recently Planktothrix rubescens blooms were reported. The aims of the study were: (1) identify and quantify the occurring species of cyanobacteria (CB), (2) identify which parameters, among those investigated in the waters, could favor their growth, (3) set up a model to identify reservoirs that need continuous monitoring due to the presences, current or prospected, of cyanobacterial blooms and of microcystins, relevant for environmental and, consequentially, for human health. Fifteen artificial reservoirs among the large set of Sicilian artificial water bodies were selected and examined for physicochemical and microbiological characterization. Additional parameters were assessed, including the presence, identification and count of the cyanobacterial occurring species, the measurement of microcystins (MCs) levels and the search for the genes responsible for the toxins production. Principal Component Analysis (PCA) was used to relate environmental condition to cyanobacterial growth. Water quality was poor for very few parameters, suggesting common anthropic pressures, and PCA highlighted clusters of reservoirs vulnerable to hydrological conditions, related to semi-arid Mediterranean climate and to the use of the reservoir. In summer, bloom was detected in only one reservoir and different species was highlighted among the Cyanobacteria community. The only toxins detected were microcystins, although always well below the WHO reference value for drinking waters (1.0 µg/L). However, molecular analysis could not show the presence of potential cyanotoxins producers since a few numbers of cells among total could be sufficient to produce these low MCs levels but not enough high to be proved by the traditional molecular method applied. A simple environmental risk-based model, which accounts for the high variability of both cyanobacteria growth and cyanotoxins producing, is proposed as a cost-effective tool to evaluate the need for monitoring activities in reservoirs aimed to guarantee supplying waters safety.

The challenge of maintaining necessary vascular and endovascular services at a referral center in Northern Italy during the COVID-19 outbreak.

OBJECTIVES: The Padova Hospital Vascular Surgery Division is located in Veneto, one of the area of the Northern Italy most hit by the Coronavirus disease 2019 outbreak. The aim of this paper is to describe the protocols adopted and to evaluate their impact during the acute phase of Coronavirus spread, focusing on the management of elective and urgent/emergent surgery, outpatients activity, and also health staff preservation from intra-hospital Coronavirus disease 2019 infection. METHODS: Several measures were progressively adopted in the Padova University Hospital to front the Coronavirus disease 2019 outbreak, with a clear strong asset established by 9 March 2020, after the Northern Italy lockdown. Since this date, the Vascular Surgery Unit started a "scaled-down" activity, both for elective surgical procedures and for the outpatient Clinical activities; different protocols were developed for health preservation of staff and patients. We compared a two months period, 30 days before and 30 days after this time point. In particular, emergent vascular surgery was regularly guaranteed as well as urgent surgery (to be performed within 24 h). Elective cases were scheduled for "non-deferrable" pathology. A swab test protocol for COVID-19 was applied to health-care professionals and hospitalized patients. RESULTS: The number of urgent or emergent aortic cases remained stable during the two months period, while the number of Hospital admissions via Emergency Room related to critical limb ischemia decreased after national lockdown by about 20%. Elective vascular surgery was scaled down by 50% starting from 9 March; 35% of scheduled elective cases refused hospitalization during the lockdown period and 20% of those contacted for hospitalization where postponed due to fever, respiratory symptoms, or close contacts with Coronavirus disease 2019 suspected cases. Elective surgery reduction did not negatively influence overall carotid or aortic outcomes, while we reported a higher major limb amputation rate for critical limb ischemia (about 10%, compared to 4% for the standard practice period). We found that 4 out of 98 (4%) health-care providers on the floor had an asymptomatic positive swab test. Among 22 vascular doctors, 3 had a confirmed Coronavirus disease 2019 infection (asymptomatic); a total of 72 swab were performed (mean = 3.4 swab/person/month) during this period; no cases of severe Coronavirus disease 2019 (deaths or requiring intensive care treatment) infection were reported within this period for the staff or hospitalized patients. CONCLUSIONS: Elective vascular surgery needs to be guaranteed as possible during Coronavirus disease 2019 outbreak. The number of truly emergent cases did not reduce, on the other side, Emergency Room accesses for non-emergent cases decreased. Our preliminary results seem to describe a scenario where, if the curve of the outbreak in the regional population is flattened, in association with appropriate hospitals containment rules, it may be possible to continue the activity of the Vascular Surgery Units and guarantee the minimal standard of care.

Impact of the environment on the health: From theory to practice.

The Erice 56 Charter titled "Impact of the environment on the health: from theory to practice" was unanimously approved at the end of the 56th course of the "International School of Epidemiology and Preventive Medicine G. D'Alessandro" held from 3rd to November 7, 2019 in Erice - Sicily (Italy) and promoted by the Study Group of "Environment and Health" of the Italian Society of Hygiene, Preventive Medicine and Public Health. The course, that included lectures, open discussions and guided working groups, was aimed to provide a general training on epidemiological and toxicological aspects of the environmental health impact, to be used by public health professionals for risk assessment, without forgetting the risk communications. At the end of the course 12 key points were agreed among teachers and students: they underlined the need of specific training and research, in the perspective of "One Health" and "Global Health", also facing emerging scientific and methodological issues and focusing on communication towards stakeholders. This Discussion highlight the need to improve knowledge of Health and Environment topic in all sectors of health and environmental prevention and management.

Kawasaki disease and cardiac involvement: an update on the state of the art.

Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. It has a self-limiting course and so far, represents the most common cause of coronary heart disease acquired in children aged between 6 months and 5 years. The inflammatory process can involve the coronary arteries with the formation of aneurysms and thrombotic occlusions with the risk of sudden death, especially in infants. Myocardial inflammation and abnormalities of cardiac contractility can occur acutely or many years after the disease onset. Therapy must be started within 10 days after the onset of symptoms to reduce the risk of heart complications. Immunoglobulin and aspirin treatment are effective in reducing heart complications. Recent studies have shown new therapeutic strategies (corticosteroids, immunosuppressive and biological drugs) in case of ineffectiveness of treatment with immunoglobulins.

Transgenic Citrange troyer rootstocks overexpressing antimicrobial potato Snakin-1 show reduced citrus canker disease symptoms.

Citrus canker is a major disease caused by Xanthomonas citri pv. citri. Snakin-1 is an antimicrobial peptide, which was previously shown to be effective against different bacterial and fungal diseases in potato, wheat and lettuce when expressed in transgenic plants. We generated transgenic Citrange Troyer citrus rootstocks constitutively expressing this peptide and 5 different transgenic lines were challenged against virulent X. citri isolates. Challenge assays conducted in vitro using detached leaves and in planta by infiltration revealed a significant reduction of the number and size of canker lesions in some of the transgenic lines.

Status of low-energy accelerator-based BNCT worldwide and in Argentina.

Existing and active low-energy Accelerator-Based BNCT programs worldwide will be reviewed and compared. In particular, the program in Argentina will be discussed which consists of the development of an Electro-Static-Quadrupole (ESQ) Accelerator-Based treatment facility. The facility is conceived to operate with the deuteron-induced reactions 9Be(d,n)10B and 13C(d,n)14N at 1.45 MeV deuteron energy, as neutron sources. Neutron production target development status is specified. The present status of the construction of the new accelerator development laboratory and future BNCT centre is shown.

Patent method for the extraction and determination of micro- and nano- plastics in organic and inorganic matrix samples: An application on vegetals.

The uncontrolled introduction into the environment of plastic polymers have caused the dispersion of plastic debries, known as microplastics (MPs), that represent an important topic for environmental and human health threats. So far, the absence of effective and efficient extraction methods of MPs (especially for plastic particles with diameters inferior than 10 µm) from complex matrices (water, food, etc.) did not allow to perform the risk estimation and, the consequent assessment of the health impact associated with the exposure to these emergent contaminants. In this paper, a new patented method for the extraction and determination of micro- and nano-plastics in organic and inorganic matrix samples is reported. The method applied in the study has been nationally and internationally protected. The code of the submitted request of international patent's extension in several country of world is PCT/IB2019/051,838 of 7 March 2019, coupled with the accepted Italian patent n. 102,018,000,003,337 of March 7 of 2018 entitled "Method for extraction and determination of microplastics in samples with organic and inorganic matrices". The method applied to our study is based on sedimentation of the particles with density higher than 1 g/cm3. The method can be applied to organic and inorganic samples as water, food, soil, waste, air, biological sample (blood, urine, tissues, etc.). After acid digestion of sample matrix, MPs are recovered by sedimentation in dichloromethane and then they are dispersed in metallic stub. Analysis is performed by SEM-EDX.•New method for the extraction and determination of total microplastics <10 µm.•The method is based on the sedimentation of particles with density higher than 1 g/cm3.•The method can be applied to organic (food, soil, biological sample, etc..) and inorganic samples.•Total micro- and nano-plastics quantification is performed by SEM-EDX.

Efficacy of ozonized water for the treatment of erosive oral lichen planus: a randomized controlled study.

BACKGROUND: Management of erosive Oral Lichen Planus (eOLP) is challenging. Currently, topical corticosteroids are widely used as first-line therapy, but they might be associated with side-effects and incomplete clinical response. Among non-pharmacological strategies, ozone at low medical concentration has proven to induce a mild activation of protective anti-oxidant pathways, thus exerting therapeutic effects in many inflammatory diseases. The aim of this randomized controlled study was to investigate the effectiveness of ozonized water in association with conventional topical corticosteroids for the treatment of eOLP. MATERIAL AND METHODS: Fifty-one patients were included in the study and randomized into 2 groups: study group (n=26) included patients receiving ozonized water treatment; control group (n=25) included patients receiving placebo treatment (i.e. double-distilled water). Treatment protocol consisted of 1-minute oral rinses, repeated for 4 times, twice a week for 4 weeks. All patients received conventional corticosteroid topical therapy (betamethasone soluble tablets, 2 rinses/day for 4 weeks). Assessment of size of lesions, sign and pain scores was performed before treatment, after 2 weeks of treatment (T1) and at the end of 4-week treatment (T2). Efficacy Index (EI) of treatment, candidiasis and relapse rates were also recorded. RESULTS: All patients experienced significant improvement of sign and pain scores with a higher rate of improvement in ozone-treated group (T1 improvement rates: Thongprasom 92.2% vs 28%; VAS pain 76.9% vs 32%; p<0.05). Pain and size reduction were significantly higher in ozone-treated group both at T1 and T2 (p<0.05). Ozone-treated group showed a higher EI at every time point (T0-T2: 72.77% vs 37.66%, p<0.01). Candidiasis (32% vs 11.5%) and relapse (40% vs 34.6%) rates were higher in control group, however the differences were not statistically significant. CONCLUSIONS: Within the limitations of this study, ozonized water seems to be effective as an adjunct therapy, in combination with topical corticosteroids, for the treatment of eOLP.