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This paper briefly describes the therapeutic mechanisms underlying hyperbaric oxygen therapy (HBOT), and reviews data concerning its effects and efficacy in Parkinson's disease (PD) and fibromyalgia (FM).The studies included in this review all evaluated the effect of HBOT in patients with diseases involving CNS. The PubMed databases were searched from 1980 to September 2019 using the keywords: 'hyperbaric oxygen therapy', 'fibromyalgia' and 'Parkinson's disease'.HBOT is already indicated in various diseases and is the subject of continuous research and development. Data from models of PD show that it may play a neuroprotective role because of its ability to reduce oxidative stress and neurodegeneration, and protect against neuronal apoptosis. It is effective in improving the symptoms and quality of life of fibromyalgia patients, and rectifies abnormal brain activity in pain-related areas. Evidence from animal studies supports its use as an alternative treatment for other rheumatic diseases as it alleviates pain and reduces inflammation.Data mainly from animal studies support the use of HBOT in the treatment of PD and rheumatic diseases, but further work is necessary to clarify its therapeutic role in patients with these chronic disorders.

Aim: To use 2D speckle-tracking echocardiography, and conventional and tissue Doppler echocardiography to detect subclinical left ventricular myocardial dysfunction in patients with rheumatoid arthritis (RA). Methods: Thirty RA outpatients were assessed before and after 18 months of treatment with anti-TNF drugs, along with 30 healthy controls. Cardiovascular risk was assessed by means of ultrasound carotid assessment and comprehensive echocardiographic evaluation (conventional and speckle-tracking calculation). Results: The speckle-tracking analyses were significantly different between the two groups, with global longitudinal strain deformation in the apical four-chamber view being significantly lower in the RA patients (median: 18.78%, interquartile range [IQR]: 15.80–20.82% vs 20.16%, IQR: 19.03–21.89%; [p, Lay abstract The different structures of the heart may be affected by rheumatoid arthritis (RA)-related inflammation, with the most frequent lesion being conduction defects, followed by pericarditis, cardiomyopathy and valve disease. We demonstrated, in a study involving 30 RA patients and using speckle-tracking echocardiography, that left ventricular myocardial longitudinal strain was impaired in the RA patients, in the absence of any clinical or other echocardiographic evidence of cardiovascular disease. The results suggest that inflammation is associated with myocardial alteration, as it returns to healthy controls levels upon therapy with anti-TNF drugs.

To correlate the expression of microRNAs (miRNAs) 146a/b, 16, the 17-92 cluster and 181a in salivary and plasma samples taken from primary Sjögren's syndrome (pSS) patients with clinical, laboratory and ultrasound findings.Plasma and salivary samples were collected from 28 patients with pSS according to 2012 ACR and/or 2016 ACR/EULAR criteria (27 females, mean age 64.4±10.1 years, mean disease duration 10.7±6.9 years), and from 23 healthy subjects used as controls. The following patient data were recorded: ESSDAI and ESSPRI scores, anti-SSA and anti-SSB antibody status and laboratory data, Schirmer's test, ultrasound scores of the four major salivary glands according to Cornec et al., and concomitant treatments. The retro-transcribed and quantified miRNAs were: miR16-5p, miR17-5p, miR18a-5p, miR19a-5p, miR19b-1-5p, miR20a, miR92-5p, miR146a-5p, miR146b-5p, miR181a-5p.SS patients had higher expression of salivary miR146a than gender- and age-matched controls (p=0.01). Spearman's regression analysis revealed that salivary miR146b was significantly more expressed in the patients with worse ESSPRI scores (p=0.02), whereas salivary miR17 and 146b and plasma miR17 expression was lower in the patients with higher ultrasound scores (respectively p=0.01, p=0.01 and p=0.04). Salivary miR18a expression was significantly increased in the patients who were anti-La/SSB positive (p=0.04). Neither salivary nor plasma miRNAs correlated with disease duration or concomitant therapies.Our data show that salivary mi146a may represent a marker of the disease, and that the expression of salivary miR17, 18a and 146b may be altered in patients with pSS, and associated with worse ultrasound and ESSPRI scores and anti-La/SSB positivity.

Background Cardiovascular (CV) mortality and morbidity is increased in rheumatoid arthritis (RA). Studies found a more than two- three-fold higher prevalence of ischaemic heart disease in RA patients compared to controls. However, a number of studies indicate that RA is also associated with various non-atherosclerotic CV manifestations. The inflammatory processes in RA may affect different structures of the heart: the most characteristic lesions are conduction defects, but other less frequent manifestations are pericarditis, cardiomyopathy and valve disease. Objectives The aim of this study was to evaluate left ventricular myocardial function with two-dimensional speckle tracking echocardiography (STE), in addition to conventional Doppler and tissue Doppler echocardiography, in order to detect subclinical left ventricular myocardial dysfunction in patients with RA. Methods The study involved 30 outpatients who fulfilled the 2010 ACR/EULAR) criteria for RA (11 males and 19 females; mean age 54.63±9.36 years, median disease duration 2 years), at baseline at after 18 months of treatment with anti-TNF drugs and 30 healthy controls matched in terms of age, gender and other anthropometric characteristics. All patients underwent a complete physical examination and routine laboratory analysis. CV risk profiles were assessed by means of standard ECG, conventional and stress trans-thoracic echocardography with the measurement of CFR, carotid ultrasonography and pulse wave velocity (PWV). Two-dimensional echocardiographic images were obtained using the apical 4-chamber view at a high frame rate of 70–80 frames/s, and three cardiac cycles were stored in cine-loop format for off-line analysis using commercially available QLAB 9 software (Philips Medical System, USA) in order to assess global longitudinal strain (GLS). Results None of the patients showed any signs or symptoms of CV disease, pulmonary involvement, or any other complication. The results of the speckle tracking analysis were significantly different between the two groups, with GLS being significantly lower in the RA patients compared to healthy controls (GLS%: 18.51±9.63 vs 20.23±2.71; p Conclusions GLS measured by means of speckle tracking echocardiography was impaired in RA patients in the absence of any clinical evidence of CV disease and echocardiographic evaluations negative. This data suggests an early myocardial alteration. Reference [1] Baktir AO, Sarli B, Cebicci MA, et al. Preclinical impairment of myocardial function in rheumatoid arthritis patients. Detection of myocardial strain by speckle tracking echocardiography. Herz2015;40(4):669–74. Disclosure of Interest None declared

Background It has been demonstrated that miRNAs expressed in PBMCs and salivary glands of patients affected by Sjogren’s Sydrome (SS) could be involved in the epigenetic control of the disease. Objectives We aimed to compare the concentration of miRNA-146a/b, 16, 17–92 cluster and 181a in salivary and plasmatic samples collected from SS patients and healthy controls and to evaluate the associations with clinical, laboratory and ultrasound findings. Methods We collected plasmatic and salivary samples from 28 patients (27 females, mean age 64.4±10.1 years, mean disease duration 10.7±6.9 years) affected by primitive SS according to ACR 2012 and/or 2016 criteria and 23 matched healthy controls. In the group of patients, the following data were recorded: ESSDAI and ESSPRI scores, anti-SSA and anti-SSB status and laboratory data, Schirmer’s test, ultrasound scores of the four major salivary glands according to Cornec et al. and concomitant treatments. The following miRNA were extracted, retro-transcribed and quantified: miR16–5 p, miR17–5 p, miR18a-5p, miR19a-5p, miR19b-1–5 p, miR20a, miR92–5 p, miR146a-5p, miR146b-5p, miR181a-5p. Results The concentration of miRNAs evaluated in plasma and saliva did not significantly match both in patients and in controls, underlining a different modulation in their expression according to the corporeal district. In patients and controls miRNAs16, 17 and 20 were hyper-expressed and miRNA146b and 181 hypo-expressed in salivary samples compared to plasmatic ones. Salivary miRNAs 18a and 146a were hyper-expressed in patients and hypo-expressed in controls, when compared to plasmatic concentrations. Comparing salivary and plasmatic patients’ miRNAs concentrations to those of healthy subjects, plasmatic miRNA16 and 181a were significantly more expressed in patients than in controls (two-tailed Wilcoxon test and Student’s T test for unpaired samples). In SS patients, salivary miRNA 181 and 146a were significantly increased in older subjects (p=0.01 and p=0.04 respectively). Spearman’s correlation revealed that salivary miRNA146b was significantly hyper-expressed in patients with worse ESSPRI scores (p=0.02); on the contrary, salivary miRNA17, 146b and plasmatic miRNA17 were reduced in patients with higher scores at ultrasound evaluation (p=0.01, p=0.01 and p=0.04 respectively). Plasmatic concentration of miRNA18a was increased in patients with less lachrymal production at Schirmer’s test (p=0.01) and plasmatic concentration of miRNA17 was reduced in patients with higher ESR values (p=0.01). Salivary miRNA18a was significantly increased in patients with anti-La/SSB (p=0.04; Mann-Whitney U test for unpaired samples). Salivary and plasmatic miRNAs did not correlate with disease duration and concomitant therapies. Conclusions Our data show that the expression of salivary miRNAs 17, 18a and 146b may be altered in SS patients and associated with worse ultrasound and ESSPRI scores and anti-La/SSB positivity. Disclosure of Interest None declared

Joint damage predicts functional limitation and mortality in psoriatic arthritis patients, but evidence from cohort studies supports the idea that early diagnosis and treatment are beneficial. Given the revolution in the treatment of rheumatoid arthritis, treating to targets and close control have become attractive concepts in the clinical management of psoriatic arthritis. The evidence in favor of the use of conventional disease modifying antirheumatic drugs is weak, but observational study results suggest that the early use of anti-TNF drugs should be encouraged. Ustekinumab and apremilast are useful alternatives for patients failing on previous anti-TNF therapy, and ampremilast can also be used for the first-line treatment of selected cases (i.e., patients who cannot tolerate other first-line treatments).

Objective Determine in a cohort of patients with normal hearing and chronic tinnitus if self-reported history for temporomandibular joint (TMJ) dysfunction and a positive modulation of tinnitus in the TMJ region could be suggestive of an underlying TMJ disorder. Patients and methods The study included 226 patients presenting to the Head and Neck Service of our University Hospital. Following audiological and somatic tinnitus evaluation, patients were divided into two groups. The study group (n = 134) included subjects that met both the following criteria: A) a self-reported history for TMJ dysfunction and B) a positive modulation of tinnitus following somatic maneuvers in the TMJ region. The control group (n = 92) included patients with similar demographic and tinnitus characteristics that did not meet the proposed criteria for somatic tinnitus. Afterwards, patients underwent clinical TMJ evaluation in the Service of Clinical Gnathology of our University. Results One hundred thirty-one patients (57.9%) received a clinical diagnosis of TMJ disorder according to DC/TMD Axis I; 79.1% in the study group and 27.2% in the control group. Ninety-five (42.1%) patients were negative for TMJ disorders; 20.9% in the study group and 72.8% in the control group. A significantly higher number of TMJ disorders was found in patients in the study group compared to the control group (p

Background Metabolic syndrome (MeS) is a cluster of cardiovascular (CV) risk factors (obesity, dyslipidemia, hypertension, alterations in glucose metabolism, and insulin resistance) whose prevalence is increasing particularly in devoloped countries. In comparison with the general population, patients with ankylosing spondylitis (AS) are at increased risk of cardiovascular (CV) disease, which is one of the main causes of mortality among them. Objectives The aim of this study was to identify the relationship between MeS and disease activity in AS patients, and evaluate the the effect of anti-tumour necrosis factor (TNF) therapy. Methods The study involved 30 outpatients who met the New York diagnostic criteria for AS: 14 males and 16 females; mean age 53.07±10.73 years; mean disease duration 5.03±4.06 years. All of the patients were being treated with DMARDs and anti-inflammatory drugs, but none had received any biological agents or steroids at baseline. The patients underwent laboratory tests (lipid profile and glucose levels), a clinical and standard echocardiographic examination, carotid ultrasonography (including the assessment of intima-media thickness and pulse wave velocity), and speckle tracking echocardiography (STE) of the left ventricle (LV) using Philips QLAB software to evaluate their CV risk profiles. Functional impairment and disease activity were assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI). All of the patients were evaluated at baseline and after 12 months of anti-TNF treatment. The data were statistically analysis using non-parametric chi-squared and Mc-Nemar tests, and the Wilcoxon-Mann-Whitney test. Results Before starting anti-TNF therapy, the cohort was divided into two groups: those with MeS (25%) and those without. The patients with MeS higher BASDAI scores (chi-squared test: 4.85; p=0.03). After 12 months of follow-up, there was a statistically significant improvement in global longitudinal strain (GLS) in both groups: from a baseline median of 19.94 (IQR 18.66–20.78) to a median of 21.46 (IQR 20.37–22.69) (p=0.02) in the non-MeS group, and from a baseline median of 18.88 (IQR 16.00–19.35) to 19.54 (IQR 18.21–19.98) (p=0.04) in the MeS group. No other changes in CV parameters were observed. The improvement in BASDAI scores was greater in the MeS group, but the difference was not statistically significant. The prevalence of MeS decreased after 12 months of anti-TNF therapy, although the McNemar test showed that the decrease was of borderline significance (p=0.048). Conclusions AS patients are affected by MeS. The effects of anti-TNF drugs on MeS are still controversial, but our findings suggest that they improve CV markers such as GLS as well as disease activity. The main limitation of this study is its small sample size and short follow-up; further studies are required in order to clarify the influence of MeS on clinical therapeutic outcomes. Disclosure of Interest None declared

Purpose: 11β-Hydroxylase deficiency (11OHD) represents the second most common cause of congenital adrenal hyperplasia. It is caused by mutations in the CYP11B1 gene localized about 40 kb from the CYP11B2 gene with which it shares a homology of 95 %. The asymmetric recombination of these two genes is involved both in 11OHD and in glucocorticoid-remediable aldosteronism (GRA). Our objective was to set up an easy and rapid method to detect these hybrid genes and other kinds of deletions, to improve the molecular diagnosis of 11OHD. Methods: A set of 8 specific probes for both the CYP11B1 and the CYP11B2 genes to be used for multiplex ligation-dependent probe amplification (MLPA) analysis was designed to detect rearrangements of these genes. Results: The method developed was tested on 15 healthy controls and was proved to be specific and reliable; it led us to identify a novel chimeric CYP11B2/CYP11B1 gene in one patient that carried the known A306V mutation on the other allele. Specific amplification and sequencing of the hybrid gene confirmed the breakpoint localization in the second intron. Conclusions: The MLPA kit developed enables the detection of deletions, duplications or chimeric genes and represents an optimal supplement to DNA sequence analysis in patients with 11OHD. In addition, it can also be used to show the presence of the opposite chimaera associated with GRA.

Purpose: To investigate functional and morphological retinal changes in the long-term follow-up in subjects with type 1 diabetes mellitus (DM1) without any signs of retinal vasculopathy. Methods: Functional testing included Humphrey Matrix perimetry (30-2 threshold program) and white-on-white Humphrey perimetry (HFA, 30-2 SITA standard), while retinal nerve fibre layer (RNFL) thickness was measured by scanning laser polarimetry with variable corneal birefringence compensator. Results: Data from 20 eyes of 20 subjects with DM1 were analysed. No changes of HFA mean deviation (MD: -2.20 ± 3.44 vs. -1.63 ± 2.47; p = 0.14) and pattern standard deviation (PSD: 2.50 ± 1.71 vs. 2.28 ± 1.36; p = 0.31), and Matrix MD (-1.06 ± 3.62 vs. -1.24 ± 2.99; p = 0.65) were found after 5 years. A significant change was found for Matrix PSD between baseline and the end of follow-up (2.76 ± 0.59 vs. 3.1 ± 0.68; p = 0.0078). RNFL parameters were not changed. A significant relationship was found between HbA1c levels and changes from baseline of Matrix PSD (R2 0.29, p = 0.02). Conclusions: Progressive retinal functional impairment could be detected in DM1 subjects by frequency doubling perimetry before the onset of any overt retinal vasculopathy and functional impairment seems to be significantly related to glycaemic control.

The purpose of the present work was to evaluate the macular sensitivity of patients with lamellar macular hole (LMH) by means of microperimetry, and to explore the relationships between macular function, LMH anatomical characteristics and vitreous status.A total of 39 eyes from 37 patients with a diagnosis of LMH and 20 age-matched control subjects were enrolled. All patients underwent a complete ophthalmological examination including visual acuity testing (logMAR) and MP1 microperimetry. LMHs were quantitatively and qualitative characterised by spectral domain optical coherence tomography (OCT) in terms of base and apex diameter, depth, central foveal and perifoveal thickness, splitting location and integrity of outer retina layers. B scan ultrasonography was performed in order to characterise the vitreoretinal relationships.Mean total (17.2 ± 2.2 vs 19.6 ± 0.5 dB, respectively, p0.0001) and mean central (16.1 ± 3.2 vs 19.2 ± 0.7 dB, p0.0001) retinal sensitivity were significantly reduced in LMH eyes in comparison with controls. Best corrected visual acuity (BCVA) (0.15 ± 0.15 vs 0.03 ± 0.06 logMar, p = 0.001) and central retinal thickness (329.05 ± 59.3 vs 265 ± 28.5 μm, p0.0001) were significantly worse in LMH eyes in comparison with controls. In our population, mean total and central retinal sensitivity showed a moderately significant relationship with LMH depth (R(2) 0.18, p = 0.006, R(2) 0.14, p = 0.02, respectively). In all, 38% of LMH eyes (15/39) showed focal interruptions of the inner-outer segment junction with lower values of BCVA and macular sensitivity. An incomplete posterior vitreous detachment with vitreopapillary adhesion was found in 48.7% (19/39) of patients with LMH.Eyes with LMH show an impaired macular function, which is partially related to LMH depth and is more pronounced in eyes with outer retinal layers abnormalities.

PURPOSE The purpose of this study was to assess long-term functional and structural retinal changes in patients with neovascular age-related macular degeneration treated with intravitreal 0.5 mg ranibizumab. METHODS Eighteen patients with neovascular age-related macular degeneration have been evaluated in this retrospective 24-month follow-up study. All patients have been treated with 3 injections of 0.5 mg ranibizumab 1 month apart and retreated according to predefined criteria. At baseline, all patients were subjected to visual acuity, fluorescein angiography, MP1 microperimetry, and Stratus optical coherence tomography. Although visual acuity and optical coherence tomography were repeated 28 +/- 2 days after each injection, MP1 was performed at 6, 12, and 24 months. RESULTS Seventeen of 18 and 14 of 18 patients completed 12 and 24 months of follow-up, respectively. Mean retinal sensitivity significantly improved from 3.89 +/- 3.0 dB to 7.33 +/- 4.11 dB at 24 months (P = 0.024). Mean visual acuity improved from 48.67 +/- 8.59 to 59.17 +/- 16.45 at 24 months (P = 0.049). Visual acuity improved to >or=15 letters in 33.3% (6 of 18) of patients and

Purpose The purpose of this study is to report the first case, to our knowledge, of intracoital subfoveal hemorrhage occurring 1 hour after tadalafil premedication in a patient with previously undiagnosed retinal angiomatous proliferation and erectile dysfunction. Methods This is an interventional case report. The patient underwent Snellen vision acuity measurement, anterior and posterior segment biomicroscopy, and indirect ophthalmoscopy. Optical coherence tomography, fluorescein angiography, and indocyanine green angiography were also performed as needed. Recombinant tissue plasminogen activator 100 μg/0.1 mL and 0.3 mL pure SF6 gas were injected in the vitreous on presentation. Four days later, the patient received 1.25 mg/0.1 mL of intravitreal bevacizumab. Results One day after recombinant tissue plasminogen activator and gas injection, visual acuity rose to 20/60-2. A week later, visual acuity was unchanged, and the subretinal hemorrhage displaced from the foveola. Optical coherence tomography showed a marked regression of submacular thickening. Conclusion Despite strict time correlation, the submacular hemorrhage cannot be unequivocally attributed to tadalafil assumption because many other risk factors are to be considered: the Valsalva maneuver above all. Nonetheless, a suspicion should be raised, at least as a cofactor, given the drug mechanism of action and the report of vascular abnormalities bleeding in the literature, including cerebral arterovenous malformation and epistaxis. Caution should be exercised in the prescription of phosphodiesterase type 5 inhibitors to patients with known vascular abnormalities including retinal and choroidal abnormalities: retinal angiomatous proliferation, classic and occult neovascularization of any origin, and also, possibly, hemangioma.

Purpose: To evaluate prospectively, on a long-term range, the clinical outcomes of transpupillary thermotherapy (TTT) as primary treatment of selected choroidal melanoma. Methods: Seventy-seven eyes of 77 patients affected by small posterior choroidal melanoma were treated with TTT as a sole treatment, using an infrared diode laser at 810 nm according to a standard procedure. Follow-up was longer than 36 months. Results: Seventeen tumours (22%) were parapapillary (PP) and 60 tumours (78%) were non-parapapillary (NPP) in location. Mean follow-up was 55.2 ± 17.9 months in PP tumours and 44.3 ± 23.7 months in NPP tumours. Thirteen (76%) PP tumours and 55 (92%) NPP tumours regressed (P > 0.05). Nine tumours recurred: seven were retreated using Iodine-125 brachytherapy and two were enucleated (both parapapillary). Four patients (5%) developed liver metastasis and died during follow-up. Tumour thickness was found to be predictive of recurrence (odds ratio: 4.3). Complications were found in 20 eyes (26%): macular pucker in 11 (14%), macular oedema in three (4%), retinal vein occlusion in six (8%), vitreous and subretinal haemorrhage in two (3%) and neovascular glaucoma in three (4%). PP tumours had more local complications (but this was not statistically significant; P > 0.05). Complications appeared more frequently in tumours treated with more than one TTT session (P = 0.01), and time-risk to develop intraocular complications seems longer in the PP group, without reaching statistical significance (P = 0.07). Conclusion: TTT may be a clinically effective method for conservative treatment of selected, non-parapapillary, small posterior choroidal melanoma.

Purpose To compare long-term choroidal vascular changes after iodine-125 brachytherapy (IBT) versus transpupillary thermotherapy (TTT) used as primary treatment of small choroidal melanoma. Methods Ninety-five small choroidal melanomas were randomized: 49 eyes with TTT and 46 eyes with IBT alone. Fluorescein and indocyanine green angiography (ICGA) were performed at 3-month intervals during the first year, and every 6 months thereafter. Results Mean follow-up was 56.2 months (range, 24–118 months; SD, 22.6). Tumor regressed in 45 (92%) TTT-treated vs 45 (98%) IBT-treated eyes (p=0.397). Four TTT-treated and one IBT-treated tumor recurred. Occlusion of choriocapillaris was present in all TTT and IBT cases. Closure of medium and large choroidal vessels was observed in 17 (35%) TTT-treated vs 44 (96%) IBT-treated eyes (pConclusions The pattern of tumor choroidal vascular changes following IBT and TTT differs. TTT is less effective in closing all tumor vasculature. The role of long-term choroidal vascular remodeling observed after these two treatments needs longer follow-up.

(2009). “Ego tanquam centrum circuli:” La Vita nuova, percorso di reminiscenza e psicocosmogramma. Italian Culture: Vol. 27, No. 1, pp. 5-23.

PURPOSE. To calculate the reliability of an eye-dedicated triaging system named Rome Eye Scoring System for Urgency and Emergency (RESCUE). METHODS. There were four coding parameters: pain, redness, loss of vision, and risk of open globe. Each parameter is assigned a score, the sum of which allows color coding. There were 1000 consecutive patients divided into urgent (U) or non-urgent (NU) based upon diagnosis, need for treatment, hospitalization, and/or follow-up visit. Correlation between RESCUE triage scoring as assigned by the nurse on presentation and urgency as estimated retrospectively was calculated. Accuracy, sensitivity, and specificity have been calculated. False positives (FP) have been defined as patients assigned a RESCUE green or yellow code while retrospectively judged NU and false negatives (FN) have been defined as patients assigned a white code despite being considered U. R ESULTS. Of 1000 patients, 332 (33.2%) were classified as U and 668 (66.8%) NU. The difference in RESCUE scoring between U and NU patients was significant (p