António Diogo Paiva

Desenvolvimento da linguagem em crianças com implante coclear: terá o gênero alguma influência?

PURPOSE:to evaluate the influence of gender in the development of language skills in children with severe to profound sensorineural deafness after cochlear implant.METHODS:thirty children were studied, 12 females and 18 males, aged between 8 years and 1 month and 10 years of age, with severe to profound congenital bilateral sensorineural deafness with cochlear implant. The language structures analyzed were semantics, morphosyntax and phonology. The assessment tool used was the Language Observation Grid - school level.RESULTS:the average hearing age was of 72 months for females and 72.7 months for males. The scores obtained in the three linguistic structures were statistically similar between genders. Into each structure, the comparasion of each test, were also similar.CONCLUSIONS:gender did not influence the development of oral language in children with cochlear implants, in the three linguistic structures studied.

COCHLEAR IMPLANTS AND TELEPHONE USE: PERFORMANCE ASSESSMENT IN ADULT PATIENTS

Introduccion: El uso de telefono en la comunicacion diaria por los pacientes con perdida auditiva profunda, a los que se habia insertado el implante coclear, y la interaccion social de dichos pacientes, permite aumentar su independencia y su autoestima. El uso de telefono es una habilidad, en la que, por definicion, se entiende el habla sin ayuda de lectura de labios y sin otras senales visuales.

Cochlear implantation in children with anomalous cochleovestibular anatomy

OBJECTIVE The aim of the study is to assess the audiological and surgical outcome after cochlear implantation in children with inner ear malformation and to compare them with a group of congenitally deaf children implantees without inner ear malformation. INTRODUCTION Children with profound sensorineural deafness with malformations of the inner ear represent a challenge, accounting to 5-15% of congenital sensorineural deafness. These cases were originally regarded as a contraindication for cochlear implant surgery. METHODS Retrospective study of 26 patients with congenital inner ear malformation, from a total population of 329 cochlear implant patients. Radiological evaluation with high resolution computed tomography and magnet resonance was performed to all patients in order to evaluate all the preoperative conditions. All patients were tested using European Portuguese word discrimination tests (monosyllabic test, number test and sentences test), capacity of auditory performance (CAP) and speech intelligibility rating (SIR). RESULTS In all 7.9% of deaf children in our center study have inner ear abnormalities. All children underwent successful implantation. CAP yielded an average 7.1 (+/-1.7), SIR 4.3 (+/-1.0). The children without inner ear abnormalities did not achieve statistically significant better scores. Two children had a perilymph gusher, and there were no other complications. CONCLUSION Cochlear implantation can be successfully performed in children with inner ear malformation. Audiological performance after cochlear implantation in malformed inner ears is comparable to that found in other congenitally deaf patients. The risk of CSF leak is associated with inner ear abnormalities and should be anticipated during surgery.

SAT0324 Increased frequencies of circulating CXCL10-, CXCL8- and CCL4-producing monocytes and SIGLEC-3-expressing myeloid dendritic cells in systemic sclerosis patients

Background Systemic sclerosis (SSc) is an inflammatory and fibrotic disease characterized by vascular dysfunction, excessive extracellular matrix deposition and immune dysregulation. Recent observations suggest that monocytes and dendritic cells (DCs) might be involved in SSc; including cell recruitment, trafficking, activation and an enhanced pro-fibrotic phenotype. Hence these cells might be important contributors to the disease pathogenesis. However, detailed analysis of circulating monocytes and DCs in SSc in relationship to disease activity has not been performed so far. Objectives To investigate the ex vivo pro-inflammatory properties of classical and non-classical monocytes as well as myeloid dendritic cells (mDCs) in SSc patients in relationship to disease activity. Methods This study enrolled 43 SSc patients, 30 classified as limited cutaneous SSc (lcSSc) and 13 as diffuse cutaneous (dcSSc). The healthy control group (HC) included 20 age- and gender- matched individuals. The Spontaneous production of CXCL10, CCL4, CXCL4 and IL-6 was intracellularly evaluated in classical and non-classical monocytes and Siglec-3-expressing mDCs from peripheral blood using flow cytometry. In addition, the production of these cytokines was determined upon toll like receptor 4 (TLR4) plus Interferon-γ (IFN-γ) in vitro stimulation. Results The frequency of non-classical monocytes spontaneously producing CXCL10 was increased in both lcSSc and dcSSC subsets of SSc patients (p<0.05) and CCL4 was augmented in the dcSSc patient subset (p<0.05). The proportion of CCL4 producing- mDCs were also elevated in dcSSc patients (p<0.01) and the percentage of mDCS producing CXCL10 only in lcSSc patients (p<0.05 compared to HC, but p<0.01 comparing to dcSSc). Upon in vitro stimulation the frequency of non-classical monocytes expressing CXCL8 was increased in both patient groups (p<0.01) and mDCs expressing CXCL8 only in lcSSc (p<0.01). SSc patients characterized by the presence or history of lung fibrosis, displayed a higher frequency of non-classical monocytes expressing CCL4 and CXCL10 in dcSSc patients as compared to those without this clinical manifestation (p<0.01 and p<0.05 respectively). Strikingly, the percentage of classical monocytes producing CXCL8 was augmented upon in vitro stimulation in lcSSc patients with lung fibrosis as compared to those without (p<0.01). No differences were found in the percentage of IL-6 producing cells. Conclusions These data point towards a role of activated non-classical monocytes and mDCs producing enhanced levels of proinflammatory cytokines in SSc, potentially contributing to lung fibrosis. Acknowledgements TC is supported by a grant from the Portuguese national funding agency for science, research and technology: Fundação para a Ciência e a Tecnologia [SFRH/BD/93526/2013]. Disclosure of Interest None declared

RESULTS OF COCHLEAR IMPLANTATION IN CHILDREN WITH CONGENITAL CYTOMEGALOVIRUS INFECTION VERSUS GJB2 MUTATION

Background: Children with congenital cytomegalovirus (CMV) infection face a bigger risk of neurological deficits and developmental delays associated with sensorineural hearing loss (SNHL). Their rehabilitation with a cochlear implant (CI) may therefore be inferior to the paediatric population in general. This study describes post-implant outcomes in children with CMV-related deafness and compares them to children with genetic deafness caused by GJB2 mutation (connexin 26) rehabilitated at the Centro Hospitalar e Universitário de Coimbra, Portugal.

A1.10 Human bone marrow-derived mesenchymal stromal cells strongly inhibit cytokine production by naive, memory and effector CD4+ and CD8+ T cells from rheumatoid arthritis patients, independently of disease activity status

Background and objectives Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by autoimmune activation leading to local and systemic consequences. Self-reactive T cells play a decisive role in the initiation and maintenance of the disease process. This disease course has been deeply modified by disease-modifying anti-rheumatic drugs that block pro-inflammatory cytokines, but still more than 1/3 of patients do not respond adequately to treatment. To overcome this limitation, mesenchymal stromal cells (MSC) based therapies have been recently explored. MSC are a population of adult non-hematopoietic stem cells with the ability to immunomodulate different cells of the immune system. The aim of this study was to verify the immunomodulatory activity of bone marrow (BM)-derived MSC on peripheral blood helper (Th) and cytotoxic T cells (Tc), distributed among their different functional compartments (naïve, central memory, effector memory and effector) from RA patients and healthy individuals. Materials and methods To this purpose we preformed co-cultures with mononuclear cells and BM-MSC from 12 RA patients and 8 controls during 20 h in a ratio of 2:1 (MNC:BM-MSC). Then, T cells were activated with PMA and ionomycin for 4 h to induce cytokine production by T cells. The frequency of Th and Tc cells producing cytokines (IL-2, IFN-γ, TNF-α, IL-6, IL-17 and IL-9) among the different functional compartments was measured by flow cytometry. Moreover, IL-4, IL-10, TGF-β and CTLA-4 mRNA expression was assessed after cell sorting of CD4+ and CD8+ T cells. Results BM-MSC clearly induced a decrease in the frequency of CD4+ and CD8+ T cells producing pro-inflammatory cytokines (for all the cytokines analysed) in all functional compartments and in both groups under study. However, the intensity of inhibition varied with the cytokine and the T cell functional compartment. Regarding the mRNA expression, in the presence of BM-MSC, we observed an increase of IL-4, IL-10, TGF-β and CTLA-4 in purified CD4+ T cells for both groups, although in a lower extent in RA patients. Likewise, BM-MSC induced an augment of mRNA levels of the abovementioned molecules in CD8+ T cells, although a more pronounced mRNA expression was observed in RA patients, excepting for IL-4, which expression decreased in both groups. Conclusions Our data show that BM-MSC effectively inhibit pro-inflammatory cytokines production by Th and Tc in all functional compartments and increase the mRNA expression of anti-inflammatory molecules in both T cell subpopulations. These results support their potential utility in the treatment of autoimmune diseases.

Auditory rehabilitation after cochlear implantation in adults with hearing impairment after head trauma

Abstract Introduction In this paper, the authors analyze the auditory rehabilitation after cochlear implantation in adults with hearing impairment after head trauma, comparing their performance with that of other cochlear implant (CI) adult users who have post-lingual hearing impairment with other etiologies. Methods The participants were divided into two groups: group 1 (N = 14) composed of CI adult users who have acquired severe to profound hearing loss after head trauma; group 2 (N = 231) composed of CI adult users who have severe to profound hearing loss from other etiologies. Performance was assessed using the following tests: tonal audiometry, speech audiometry, consonantal phonemes identification test, 100 words test, 100 words through the telephone test, monosyllables test, numbers test, sentences test, and sentences through the telephone test. Results Average results from group 1 were lower when compared with those of group 2 in all the tests used. No statistically significant difference was found for most tests. Statistically significant difference was found for consonantal phonemes identification test, 100 words through the telephone test, monosyllables test (when analyzed regarding the phonemes correctly repeated), and sentences through the telephone test. Discussion The performance of the group of CI adult users who have acquired hearing impairment after head trauma was globally lower than that observed on the group of hearing impairment with other etiologies. However, the difference was not statistically significant for most tests. Despite this difference in performance, the results from the group of CI adult users who have acquired hearing impairment after head trauma show the effectiveness of auditory rehabilitation through cochlear implantation in these situations.

AB0144 Increased frequency of interleukin-2 production by th17 and tc17 lymphocytes in peripheral blood of systemic sclerosis patients

Background The pathogenesis of systemic sclerosis (SSc) is largely unknown, although proinflammatory cytokines are considered to play a central role. We hypothesized that Th17 and/or Tc17 cell populations and cytokine expression may be altered in SSc. Objectives Our purpose was to investigate the pattern of expression of proinflammatory cytokines by peripheral blood (PB) IL-17+ T cell populations in SSc and to explore clinical associations. Methods This study included 41 SSc patients and 20 age- and sex-matched healthy controls (HC). All SSc patients fulfilled the American College of Rheumatology Criteria for the classification of SSc and were classified according to LeRoy et al. as having limited cutaneous SSc (lSSc, n=29) or diffuse cutaneous SSc (dSSc, n=12). A clinical evaluation was made, including disease duration, disease activity as measured by the European Scleroderma Study Group criteria, modified Rodnan skin score (mRSS), digital necrosis and target organs’ involvement. The autoantibody profile was collected from medical records. Each participant was submitted to a blood sample collection, which was processed in order to separately analyze the intracellular expression of IL-2, TNF-α and IFN-γ in IL-17+ T cell populations, within the CD4 and CD8 T cell subsets. Data was statistically analyzed using the SPSS® version 20.0 for windows. Mann-Whitney test was used to evaluate differences between groups. Correlations between continuous variables were assessed by Spearman’s correlation coefficient. P values < 0.05 were considered statistically significant. Results The mean age was 56.1±11.8 and 52.0±9.9 years for SSc patients and HC respectively. Females represented 78% of the SSc group and 80% of the HC. The patients had a mean mRSS of 11.32±7.76 and mean disease activity of 2.76±2.44. The frequency of PB Th17 and Tc17 cells was not statistically different in SSc patients when compared to HC. The percentage of Th17 and Tc17 cells expressing IL-2 was significantly higher in SSc patients than in HC (p<0.001 and p=0.006, respectively). There were no differences in the frequency of Th17 and Tc17 cells expressing either TNF-α or IFN-γ between patients and controls. There were no differences between lSSc and dSSc patients regarding the frequency of IL-2, TNF-α and IFN-γ expression among Th17 or Tc17 cells populations. We had similar negative findings regarding disease duration and internal organs’ involvement. The frequency of IL-2-producing Th17 cells showed a positive correlation with mRSS (p=0.002). Conversely, the frequency of IL-2-producting Tc17 cells presented a positive correlation with disease activity (p=0.021). SSc patients with history of digital ulcer presented higher frequencies of IL-2 expression among Tc17 cells (p=0.001). Conclusions IL-2-producing Th17 and Tc17 cells frequency is higher in SSc than in HC, no differences being found between the two clinical subtypes of the disease. The frequency of IL-2-producing Tc17 cells was correlated with disease activity whereas the frequency of IL-2-producing Th17 cells was correlated with the extension of skin involvement. These findings support the hypothesis that IL-2 produced by Th17 and Tc17 cells may be involved in the pathological process of SSc, regardless of the disease subset. References Arthritis Rheum. 1992 Jan;35(1):67-72. Disclosure of Interest None Declared

AB0146 Increased frequency of th1 and tc1 lymphocytes producing tumor necrosis factor alpha in peripheral blood of late-stage systemic sclerosis

Background Substantial evidence supports the implication of immune-activated cells, cytokines and chemokines in the pathogenesis of systemic sclerosis (SSc). The frequency of T cells expressing activation markers is increased in the peripheral blood (PB) of SSc patients. Proinflammatory cytokines, such as IL-2, TNF-α and IFN-γ, seem to be mostly involved in immune responses at early stages of the disease. However, discrepancies exist between the results of several studies. Objectives We undertook the present study to investigate the pattern of expression of proinflammatory cytokines by PB Th1 and Tc1 populations and to explore associations with disease duration. Methods Forty SSc patients and 18 healthy controls (HC) were included. All SSc patients fulfilled the American College of Rheumatology Criteria for the classification of SSc (limited cutaneous SSc (lSSc, n=29) or diffuse cutaneous SSc (dSSc, n=11), according to LeRoy et al.). A further subdivision was made, based upon the duration of disease, as early- (n=11) and late-stage (n=30), and these groups were individually compared with HC. A thorough clinical evaluation was performed and registered. The autoantibody profile was collected from medical records. All patients signed an informed consent and provided a PB sample, which was processed to separately analyze the intracellular expression of IL-2, TNF-α and IFN-γ in Th1 and Tc1 cell populations. Data was statistically analyzed using the SPSS® version 20.0 for windows. Mann-Whitney and Kruskal-Wallis tests were used to evaluate differences between groups. Correlations between continuous variables were assessed by Spearman’s correlation coefficient. P values < 0.05 were considered statistically significant. Results The mean age was 56.0±11.9 and 51.7±9.9 years for SSc patients and HC respectively. Females represented 77.5% of SSc and 83.3% of the control group. The mean disease duration was 9.6±8.55 years, the mean mRSS was 11.60±7.65 and the mean disease activity was 2.74±2.47. The frequency of Th1 and Tc1 circulating cells was not statistically different between SSc patients and HC. The percentage of Th1 and Tc1 cells producing TNF-α was significantly higher in late-stage than in early-stage SSc (p=0.034 and p=0.005, respectively). The percentage of Tc1 cells producing IFN-γ was significantly lower in early-stage than in late-stage SSc (p=0.017). No statistically significant differences were observed between early and late-stage SSc, concerning IL-2 expression among Th1 and Tc1 cells and IFN-γ expression among Th1 cells. There were no significant association between disease subset, history of digital necrosis and internal organs’ involvement, mRSS or disease activity and the frequency of IL-2, TNF-α and IFN-γ expression among Th1 or Tc1 cells. Conclusions The frequency of TNF-α-producing Tc1 cells was higher in late-stage SSc. The potential pathogenic relevance of these observations justifies further investigation, concerning the profile of proinflammatory cytokines and their potential involvement in different stages of the disease. References Arthritis Rheum. 1992 Jan;35(1):67-72. Disclosure of Interest None Declared

AB0145 Enhanced il-8 production by monocytes in systemic sclerosis patients with pulmonary fibrosis

Background Substantial evidence supports the implication of immune-activated cells, cytokines and chemokines in the pathogenesis of systemic sclerosis (SSc). In fact, interleukin 6 (IL-6) and IL-8 play a crucial role in immunity and fibrosis, both key aspects of SSc. Recent evidence, suggests that an increase of activated circulating monocytes (Mo) on peripheral blood of SSc patients have a potential role on SSc pathogenesis. This could be the source of macrophages that accumulate in injured areas and are active producers of fibrosis-inducing cytokines. Objectives Our purpose was to investigate the pattern of expression of IL-6 and IL-8 cytokines by peripheral blood (PB) Mo and to explore clinical associations. Methods This study included 43 SSc patients and 20 healthy controls (HC). All SSc patients fulfilled the American College of Rheumatology Criteria for the classification of SSc and were classified according to LeRoy et al. as having limited cutaneous SSc (lSSc, n=30) or diffuse cutaneous SSc (dSSc, n=13). A clinical evaluation was made, including disease duration, disease activity as measured by the European Scleroderma Study Group criteria, modified Rodnan skin score (mRSS), digital necrosis and target organs’ involvement. The autoantibody profile was collected from medical records. Each participant was submitted to a blood sample collection, which was processed according to a protocol, designed to separately analyze the intracellular expression of IL-6 and IL-8 in Mo cells Data was statistically analyzed using the SPSS® version 20.0 for windows. Mann-Whitney U-test was used to evaluate differences between groups. Correlations between continuous variables were assessed by Spearman’s correlation coefficient. P values < 0.05 were considered statistically significant. Results The mean age was 56.7±12.3 and 52.0±10.0 years for SSc patients and HC respectively. Females represented 79.1% of SSc and 80.0% of the control group. The mean disease duration was 9.4±8.3 years, the mean mRSS was 12.0±8.1 and the mean disease activity was 2.8±2.4. The frequency of circulating IL-6 and Il-8-producing Mo cells was not statistically different between SSc patients and HC. The percentage of IL-8-producing Mo cells was significantly higher in patients with pulmonary fibrosis (p=0.009). No statistically significant differences were observed between early and late-stage SSc, concerning IL-6 and IL-8 expression among Mo. There were no significant association between disease subset, history of digital necrosis, mRSS or disease activity and the frequency of IL-6 and IL-8 expression among Mo cells. Conclusions IL-8-producing Mo cells frequency is higher in SSc patients with pulmonary fibrosis, no differences being found between the two clinical subtypes of the disease. These findings support the hypothesis that IL-8 produced by these cellular type may be involved in the pathological process of SSc, regardless of the disease subset. References Ann Rheum Dis. 2011 Jun;70(6):1115-21. Clin Exp Rheumatol. 2011 Mar-Apr;29(2 Suppl 65):S46-52. Disclosure of Interest None Declared