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O objetivo deste trabalho consistiu em analisar e diferenciar as principais causas e consequências da inadimplência sob diferentes dimensões. As análises do estudo foram realizadas por meio de levantamento bibliográfico. Entre as causas da inadimplência, foi preciso fazer uma diferenciação deste fenômeno entre o setor público e o privado, visto que há um conjunto de causas que trazem um grau de complexidade ao se tratar dessa questão. Na área privada, as causas da inadimplência têm praticamente as mesmas origens, destacando-se fatores conjunturais, sócio-políticos, institucionais, ligados ao serviço, falta de atualização das informações cadastrais, consumismo, falta de planejamento, restrições orçamentárias e falta de conhecimentos financeiros. Na área pública, a inadimplência dos impostos também está relacionada à fatores conjunturais, ações dos governos, problemas relacionados cobrança e incentivo da inadimplência. Em relação aos fatores conjunturais tem-se a carga tributária excessiva, legislações tributárias inadequadas e punições existentes mínimas. Referente ao consequências da inadimplência houve a distinção entre três agentes impactados. Dentre estes cita-se a perspectiva do indivíduo, das instituições e da sociedade. Na perspectiva pessoal nota-se que a inadimplência traz implicações negativas tanto financeiras, quanto sociais ou psicológicas. Em relação às instituições as principais consequências da inadimplência, é que essas, muitas vezes, têm que recorrer a empréstimos bancários, aumentando seu custo operacional, ou mesmo atrasar o pagamento de suas obrigações tributárias e fiscais. Por último, com relação a sociedade a inadimplência pode causar redução no nível de emprego e salários, problemas de saúde, maximização do número de suicídios e elevação da violência.

A demanda por serviços públicos municipais cresce, sendo imprescindível que as atividades de arrecadação e fiscalização sejam desenvolvidas de forma a combater a inadimplência, a sonegação fiscal e a ocorrência de processos em cobrança administrativa ou judicial. Esse estudo teve como objetivo identificar os determinantes da inadimplência do IPTU no município de Santa Maria (RS). Utilizou-se uma pesquisa descritiva, com abordagem quantitativa e técnicas estatísticas multivariadas. A regressão logística evidenciou que a inadimplência é influenciada pela alíquota, pela existência de área irregular, pelo aumento do valor tributável do imóvel, manifestando-se favoravelmente nas pessoas físicas, relacionando-se aos valores e localização dos imóveis, bem como as posturas dos contribuintes. Em uma perspectiva municipal, destaca-se que a identificação dos determinantes da inadimplência oportunizarão ao fisco o desenvolvimento de ferramentas objetivando a sua redução. Em relação a sociedade, o combate à inadimplência faz com que sejam reduzidas as obrigações tributárias para os contribuintes, impedindo o aumento dos impostos.

A Prefeitura de Santa Maria (RS) buscando aumentar a arrecadação própria implantou, após a vigência da Lei Federal nº 12.767/ 2012, a cobrança de débitos através do envio das Certidões de Dívida Ativa para protesto extrajudicial. O objetivo do presente artigo foi analisar o panorama dessa nova modalidade de cobrança segundo a percepção dos agentes da administração tributária municipal, no período de 2014 a 2017. Para tal, foram realizadas 10 entrevistas, que após transcrição foram submetidas a análise de conteúdo para sistematizar os dados. As unidades de análise basearam-se na literatura brasileira e internacional que trata da observância fiscal e seus paradigmas. As análises apontaram que os entrevistados em sua maioria destacaram os aspectos positivos dessa cobrança, a qual consolida-se como uma eficaz ferramenta para o combate à inadimplência perante a Prefeitura. Como limitações evidenciam-se a dificuldade de obtenção de dados segregados de receita, sugerindo-se para futuros estudos a confirmação estatística das informações bem como a análise da percepção sob a ótica dos contribuintes.

Os municípios devem promover a arrecadação dos tributos de sua competência para a realização das suas múltiplas atividades visando o bem comum dos cidadãos. No Município de Santa Maria (RS), o Imposto Sobre Propriedade Predial e Territorial Urbana - IPTU destaca-se pelo baixo nível de arrecadação, influenciado, em parte, pela defasagem da Planta Genérica de Valores. Para tanto, o estudo teve como objetivo constatar e identificar os percentuais da defasagem da Planta Genérica de Valores. Então, utilizou-se uma pesquisa descritiva, com abordagem quantitativa e técnicas estatísticas descritivas. Serviram de amostra os dados cadastrais e financeiros de 126.190 imóveis registrados no setor imobiliário. Com base na estatística descritiva, constatou-se que os valores venais e tributáveis estão abaixo do valor de mercado, devido a aplicação de redutores e defasagem da planta genérica de valores. O desequilíbrio estimado entre os valores praticados pelo mercado e pela Prefeitura através da PGV, apresentam uma defasagem média de 461,29% e 1.575,53%, respectivamente para os valores venais e valores tributáveis dos imóveis. A desatualização de ambos é perceptível em toda cidade, demonstrando a necessidade de uma revisão dos valores que compõem a base de cálculo do IPTU.

Tuftsin-PhosphorylCholine (TPC) is a novel bi-specific molecule which links tuftsin and phosphorylcholine. TPC has shown immunomodulatory activities in experimental mouse models of autoimmune diseases. We studied herein the effects of TPC ex vivo on both peripheral blood mononuclear cells (PBMCs) and temporal artery biopsies (TABs) obtained from patients with giant cell arteritis (GCA) and age-matched disease controls. GCA is an immune-mediated disease affecting large vessels. Levels of 18 cytokines in supernatants, PBMC viability, T helper (Th) cell differentiation of PBMCs and gene expression in TABs were analyzed. Treatment ex vivo with TPC decreased the production of IL-1β, IL-2, IL-5, IL-6, IL-9, IL-12(p70), IL-13, IL-17A, IL-18, IL-21, IL-22, IL-23, IFNγ, TNFα, GM-CSF by CD3/CD28 activated PBMCs whereas it negligibly affected cell viability. It reduced Th1 and Th17 differentiation while did not impact Th22 differentiation in PBMCs stimulated by phorbol 12-myristate 13-acetate plus ionomycin. In inflamed TABs, treatment with TPC down-regulated the production of IL-1β, IL-6, IL-13, IL-17A and CD68 gene expression. The effects of TPC were comparable to the effects of dexamethasone, included as the standard of care, with the exception of a greater reduction of IL-2, IL-18, IFNγ in CD3/CD28 activated PBMCs and CD68 gene in inflamed TABs. In conclusion our results warrant further investigations regarding TPC as an immunotherapeutic agent in GCA and potentially other autoimmune and inflammatory diseases.

MiRNAs are single stranded RNAs of 18–22 nucleotides. They are promising diagnostic and prognostic markers for several pathologies including tumors, neurodegenerative, cardiovascular and autoimmune diseases. In the present work the development and characterization of anti-miRNA radiolabeled probes based on peptide nucleic acids (PNAs) for potential non-invasive molecular imaging in vivo of giant cell arteritis are described. MiR-146a and miR-146b-5p were selected as targets because they have been found up-regulated in this disease. Anti-miR and scramble PNAs were synthesized and linked to carboxyfluorescein or DOTA. DOTA-anti-miR PNAs were then labelled with copper-64 (64Cu) to function as non-invasive molecular imaging tools. The affinity of the probes for the targets was assessed in vitro by circular dichroism and melting temperature. Differential uptake of fluorescein and 64Cu labeled anti-miRNA probes was tested on BCPAP and A549 cell lines, expressing different levels of miR-146a and -146b-5p. The experiments showed that the anti-miR-146a PNAs were more effective than the anti-miR-146b-5p PNAs. Anti-miR-146a PNAs could bind both miR-146a and miR-146b-5p. The uptake of fluorescein and 64Cu labeled anti-miR-146a PNAs was higher than that of the negative control scramble PNAs in miRNA expressing cells in vitro. 64Cu-anti-miR-146a PNAs might be further investigated for non-invasive PET imaging of miR-146 overexpressing diseases.

The municipalities should promote the collection of taxes of their competence to carry out their multiple activities for the common good of citizens. In the Municipality of Santa Maria (RS), the Tax on Predial and Urban Territorial Property - IPTU stands out for the low level of collection, influenced, in part, by the default. This comes from several causes and presents several consequences, which can only be softened with its ample knowledge. Therefore, the purpose of this study was to identify the determinants of IPTU default in the Municipality of Santa Maria (RS), seeking to list alternatives for its reduction. So, a descriptive research was used, with a quantitative approach and descriptive and multivariate statistical techniques. The register data and financial data of 126,190 properties registered in the real estate cadaster were sampled. Based on the descriptive statistics, the characteristics and location of the real estate were verified, showing that the sales and taxable values are below the market value, due to the application of reducers and lags of the generic plant of values. Through the observation of the payment options, a default of around 40.00% was verified, and in those, the payment installments delays were of 53.00%. The cross reference tables provided a diagnosis of default, showing that the highest indexes are in residential neighborhoods, whose average nominal income is lower than the average of the municipality; located far from the central area; predominating in registries located in tax zones, whose price of the m² of the land is lower. Through test t was verified that the average of the areas and values are lower for the group of defaulters compared to the regular ones. The logistic regression showed that the default rate is influenced by the tax rate, the existence of irregular area, the increase in the taxable value of the property, favorably manifesting in the individuals, relating to the values and location of the properties, as well as the positions of the taxpayers. Thus, the study pointed to causes to be attributed to the taxpayers, to the institution and to the economic situation. As institutional causes are including the structural and registration deficiencies that hamper collection actions. Hence, it is indispensable to restructure the collection sectors, with adjustments in equipment, computer systems and human resources. Subsequently, in order to reduce delinquency, a broad registry update and intensification of collection should be promoted, through the monitoring of payments, prioritizing the neighborhoods with the largest number of properties, with differentiated action plans for taxpayers who fail to remove a few plots, of those who are habitual debtors. For the first, soft actions; for the others, strict control of reparcelling, immediate sending of the debits for registration in the organs of credit protection and fiscal execution. It was shown that the study about the defaults brought contributions to the institution, to the academy and to the society. As suggestions for future studies it is recommended to research with defaulting taxpayers to identify their profile, income and perceptions. Os municípios devem promover a arrecadação dos tributos de sua competência para a realização das suas múltiplas atividades visando o bem comum dos cidadãos. No Município de Santa Maria (RS), o Imposto Sobre Propriedade Predial e Territorial Urbana - IPTU destaca-se pelo baixo nível de arrecadação, influenciado, em parte, pela inadimplência. Essa é derivada de várias causas e apresenta diversas consequências, as quais somente poderão ser amenizadas com seu amplo conhecimento. Para tanto, o estudo teve como objetivo identificar os determinantes da inadimplência do IPTU no Município de Santa Maria (RS), buscando elencar alternativas para sua redução. Então, utilizou-se uma pesquisa descritiva, com abordagem quantitativa e técnicas estatísticas descritivas e multivariadas. Serviram de amostra os dados cadastrais e financeiros de 126.190 imóveis registrados no setor imobiliário. Com base na estatística descritiva demonstrou-se as características e a localização dos imóveis, constatando-se que os valores venais e tributáveis estão abaixo do valor de mercado, devido a aplicação de redutores e defasagem da planta genérica de valores. Através da observação das opções de pagamento, constatou-se uma inadimplência em torno 40,00%, sendo que, dessas, o atraso das parcelas corresponde a 53,00%. As tabelas de referência cruzada oportunizaram um diagnóstico da inadimplência, demonstrando que os maiores índices estão em bairros residenciais, com rendimento nominal médio inferior à média do Município; com localização afastada da área central; predominando em cadastros situados em zonas fiscais, cujo preço do m² do terreno é mais baixo. Através do teste t constatou-se que a média das áreas e dos valores é menor para o grupo dos inadimplentes, quando comparada àquela dos adimplentes. A regressão logística evidenciou que a inadimplência é influenciada pela alíquota, pela existência de área irregular, pelo aumento do valor tributável do imóvel, manifestando-se favoravelmente nas pessoas físicas, relacionando-se aos valores e localização dos imóveis, bem como as posturas dos contribuintes. Logo, o estudo apontou causas que devem ser atribuídas aos contribuintes, à instituição e à conjuntura econômica. Como causas institucionais elenca-se as deficiências estruturais e cadastrais que dificultam as ações de cobrança. Por isso, é indispensável a reestruturação dos setores de arrecadação, com adequações de equipamentos, sistemas informatizados e recursos humanos. Posteriormente, para a redução da inadimplência, deve-se promover uma ampla atualização cadastral e intensificar a cobrança, através do monitoramento dos pagamentos, priorizando os bairros com o maior número de imóveis, e com planos de ações diferenciados para os contribuintes que deixam de quitar poucas parcelas, daqueles que são devedores habituais. Para os primeiros, ações brandas; para os demais, controle rigoroso dos reparcelamentos, envio imediato dos débitos para registro nos órgãos de proteção ao crédito e promoção de execução fiscal. Ficou demonstrado que o estudo sobre a inadimplência trouxe contribuições para a instituição, a academia e a sociedade. Como sugestão para estudos futuros recomenda-se pesquisa com os contribuintes inadimplentes para identificar o perfil, a renda e as percepções destes.

The diagnosis of cytomegalovirus (CMV) anterior uveitis in immunocompetent patients requires confirmation by polymerase chain reaction (PCR) analysis and/or intraocular antibody index (AI) assay. In this study, we analyzed the different contributions of PCR and AI to CMV diagnosis by performing one single aqueous tap. A retrospective chart review was conducted of HIV-negative patients attending the Ocular Immunology Unit of Azienda Unita Sanitaria Locale – IRCCS, Reggio Emilia, Italy, from March 2015 to April 2018 with a diagnosis of hypertensive anterior granulomatous uveitis compatible with suspected CMV etiology. Diagnosis was confirmed by real-time PCR (RT-PCR) and intraocular antibody production against CMV on aqueous humor samples. Clinical features were compared to antibody titer and diagnostic delay. Twenty-three patients with suspected CMV uveitis (13 males, 10 females, mean age 48 ± 16 years) were included in the analysis. AI was positive in 20/23 (87%) samples, and PCR tested positive in 9/23 (39%). By combining both tests, the sensitivity was 100%. Median diagnostic delay was 29 months (IQR 9–107). Diagnostic delay and antibody titer were significantly associated with glaucoma (r = 0.714, p

Objectives GCA is characterized by arterial remodelling driven by inflammation. IL-22 is an attractive cytokine which acts at the crosstalk between immune and stromal cells. We hypothesized that IL-22 might be induced in GCA and might be involved in disease pathogenesis. Methods Patients subjected to temporal artery biopsies (TABs) naive from therapy were enrolled: 27 biopsy-proven GCA, 8 biopsy-negative GCA, 21 biopsy-negative non-GCA patients. Expression of IL-22 was determined in TABs by immunohystochemistry, in plasma by ELISA, in peripheral blood mononuclear cells by real-time PCR and flow cytometry. Effects of IL-22 on viability and gene expression of primary cultures obtained from TABs were also evaluated. Results Inflamed TABs from GCA patients showed a higher expression of IL-22 and IL-22 specific receptor subunit (IL-22R1) than non-inflamed TABs. IL-22 was expressed in infiltrating immune cells and spindle shaped cells, IL-22R1 was expressed in endothelial cells. Patients with biopsy-proven GCA showed increased levels of IL-22 in plasma than patients with biopsy-negative GCA, without GCA and healthy subjects. Peripheral blood mononuclear cells from GCA patients expressed higher IL-22 transcript than healthy subjects. After stimulation in vitro with phorbol 12-myristate 13-acetate and ionomycin, the frequencies of Th22 and IL-22+ CD4+ lymphocytes were similar between patients with and without GCA. Treatment with IL-22 of primary cultures obtained from TABs increased cell viability under stress conditions and expression of B-cell activating factor. Conclusion IL-22 is increased in patients with GCA and affects viability and gene expression of arterial cells, supporting a potential role in disease pathogenesis.

Background Behcet9s disease (BD) is a systemic inflammatory disorder with unknown etiology. Uveitis and retinal vasculitis occur in 60–80% of patients during the disease course. Previous data on cytokine profiling in aqueous humor (AH) of patients with active BD-related uveitis suggested that both T helper (Th) 1 and Th17 cells are involved in immunopathogenesis [1]. Furthermore, higher levels of Natural Killer T (NKT) cells (CD3+ CD56+) have previously been found in AH of patients with BD-related uveitis as compared to other types of uveitis [2]. However, data on magnitude and patterns of cytokines in BD-related uveitis remain scarce. Objectives To examine cytokine production as well as frequency of NK and NKT cells in AH from BD patients with active uveitis as compared to patients with active Vogt-Koyanagi-Harada (VKH) disease-related uveitis. Methods AH from 8 adult patients with BD (1990 ISGB criteria [3]) and active uveitis, and from 7 patients with active VKH were analyzed. Definition of “active” uveitis included ≥2 cells in the anterior chamber (Hogan scale, 1950) and/or 2+ vitritis (Nussenblatt scale, 1990), papillitis, macular edema and retinal vasculitis with active “photo fundus”. AH from 5 subjects undergoing cataract surgery were included as controls. Cytokines9 concentrations were determined with Bio-Plex Pro-Human cytokine 27-plex assay. Frequency of NK and NKT cells was determined by flow cytometry using anti-CD3, -CD56, -CD16 antibodies. Results Higher levels of IL-1b, IL-1RA, IL-5, IL-7, IL-6, G-CSF, IFN-g, IP-10, TNF-a IL-8 and MIP1a were found in AH from patients with BD and VKH compared to controls. G-CSF and IFN-g were detected in AH from BD and VKH patients, but not in the control group. Lower levels of GM-CSF were found in BD and VKH patients, while IL-6 levels were 3000-fold increased, as compared to controls. No differences were detected between BD and VKH patients in terms of cytokine levels. However, AH from 4 BD patients showed a peculiar distinct cytokine pattern, when analyzed by unsupervised cluster analysis. Intriguingly, a higher amount of neutrophils/mL was found in AH from these 4 BD cases. Frequency of NKT (CD3+ CD56+) cells was higher in BD patients as compared to VKH, while that of NK (CD56+ CD3neg) cells was similar and that of T cells (CD56negCD3+) was lower. Finally, no difference was found between NK subsets in terms of proportion of CD16+ cells in both BD and VKH groups. Conclusions AH of both BD and VKH groups showed increased levels of IL-6, G-CSF and IFN-g, which might suggest their potential role in the immunopathogenesis of these types of endogenous uveitis. However, a distinct cytokine profile able to distinguish the two conditions remains to be identified. Additionally, our preliminary results confirm the previous observation of increased NKT cells levels in BD uveitis as compared to VKH. References El Asrar A.M., et al. Clin Immunol 2011;139:177–84. Yu H.G., et al. Clin Exp Immunol 2004;137:437–443. International Study Group for Behcet9s Disease. Lancet 1990;335:1078–80. Disclosure of Interest None declared

Background Behchet disease (BD) is a rare inflammatory small vessel vasculitis. It is a chronic systemic disorder with multiorgan damage and various clinical manifestations such as oral ulcers, genital ulcers and uveitis. Etiology is still unknown. Some gene polymorphisms have been associated with BD [1]. In addition, a high frequency of circulating Natural Killer T cells (NKT cells) has been found in BD patients respect to patients with other inflammatory uveitis such as Vogt-Koyanagi-Harada disease (VKH) [2]. Objectives The objective of this study was to characterize the cytotoxic profile of circulating Nautral Killer (NK) and NKT cells in BD patients. Methods Peripheral Blood Mononuclear Cells (PBMCs) were collected from 23 BD patients (according to 1990 ISGB criteria), 7 VKH patients (according to 2001 Revised Diagnostic Criteria) and 9 healthy subjects [3,4]. BD activity was evaluated with BD Current Activity Form 2003. Anti-CD56 and anti-CD3 antibodies were used to identify NK (CD56+CD3-) and NKT (CD56+CD3+) cells by flow-cytometry. Expression of one inhibiting receptor (NKG2A) and five activating receptors (CD16, CD69, NKG2D, Nkp30 and Nkp46) was determined on the surface of NK and NKT cells. Cytotoxic potential of NK and NKT cells was assessed through incubation of PBMCs with K526 cells in presence or absence of IL-15 followed by flow-cytometry detection of the surface marker CD107a on NK and NKT cells [5]. Results A higher frequency of NKT cells was detected in peripheral blood of BD patients than VKH patients. Compared to healthy subjects, an increased proportion of CD16 positive NKT cells was found in BD patients. Furthermore it was observed a higher percentage of NKG2D positive cells in both NK and NKT lymphocytes. No difference in the other markers was detected. In BD patients, the incubation of PBMCs with K562 cells in absence of IL-15 induced a higher percentage of NK cells expressing CD107a compared to VKH patients. Frequency of CD107a positive NKT cells was Conclusions Our study confirms previous reports about an increased level of NKT cells in peripheral blood of BD patients, but we additionally identified a cytotoxic profile of NK and NKT cells characteristic of BD patients when compared to healthy subjects and patients with VKH. Our data revealed for the first time a potential involvement of NKG2D in the pathogenesis of BD. We can speculate that NK and NKT cells of BD patients are more prone to respond to stress/danger signals when exposed on target cells leading to cyclic auto-inflammation. References Ombrello MJ. Et al. Proc Natl Acad Sci U S A. 2014, 111:8867–72. Hamzaoui K. et al. J Neuroimmunol. 2006, 175:160–8. International Study Group for Behcet9s Disease. Lancet 1990, 335:1078–80. Read RW. et al. Am J Ophtalmol. 2001, 131:647–52. Alter G. et al. J Immunol Methods. 2004, 294:15–22. Disclosure of Interest None declared

Purpose The role of uveitis, an uncommon ocular disease, is often neglected in research and treatment of autoimmune conditions. The study described the spectrum of uveitis at a referral center in North Italy, and compared that to a previously published series of patients. Methods We reviewed all patients with uveitis diagnosed from 2013 to 2015 at the Immunology Eye Unit, Arcispedale S. M. Nuova-IRCCS, Reggio Emilia, Italy. We examined patient characteristics, disease spectrum, and etiologies. Results In total, 990 cases of uveitis were identified, who were mostly female (59%) with a median age at presentation of 44 years (interquartile range = 29–57). Anterior uveitis was most frequent (53.5%), followed by panuveitis (22.8%), posterior (16.2%), and intermediate uveitis (5.5%). Anterior herpetic uveitis (15.6%), Fuchs uveitis (9.7%), and HLA-B27 positive anterior uveitis (7.7%) were the most common specific diagnoses. Compared with the previous series, we observed an increased incidence of uveitis, and a different pattern of diagnoses. Rates of herpetic, HLA-B27 positive uveitis, and presumed ocular tuberculosis were higher, but Fuchs uveitis was less frequent. Conclusions The pattern of uveitis appears to be changing, very likely due to population-level increases in infectious diseases, to the availability of new diagnostic tests and to the interdisciplinary approach used in patient diagnosis.

Objective Data on the presence of varicella-zoster virus (VZV) in temporal arteries of patients with giant cell arteritis (GCA) are controversial. We analyzed VZV infection in temporal arteries from Italian patients with temporal artery biopsy (TAB)-positive GCA, TAB-negative GCA, and controls. Methods A total of 79 formalin-fixed, paraffin-embedded (FFPE) TABs performed between 2009 and 2012 at a single institution from 34 TAB-positive GCA patients, 15 TAB-negative GCA patients, and 30 controls were retrieved. Six 5-μm sections of all FFPE TABs were cut. The first section was analyzed by immunohistochemistry using mouse monoclonal anti-VZVgE IgG1 antibody. DNA was extracted from the remaining five sections and analyzed by real-time polymerase chain reaction (PCR) for the presence of VZV DNA. For 10 of the 34 TAB-positive GCA patients, an additional 2-mm piece of frozen TAB was available. DNA was extracted from the entire 2-mm length frozen specimen and analyzed by PCR for the presence of VZV DNA. Thirty additional 5-μm sections were cut from the FFPE TABs of these 10 patients and analyzed by immunohistochemistry for the presence of VZV antigen. Results Immunohistochemical analysis detected VZV antigen in 1/34 (3%) TAB-positive GCA, 0/15 TAB-negative GCA, and 0/30 controls, and in none of the 300 sections cut from the 10 FFPE TABs positive for GCA for which the frozen specimens were available. DNA obtained from all TABs was amplifiable. VZV DNA was neither found in any of the FFPE TABs nor found in frozen TABs. Conclusion Our data do not support in Italian patients a possible role for VZV infection in the etiopathogenesis of GCA.

To characterise the polyspecific intraocular antibody synthesis in aqueous humor of patients with Fuchs uveitis and other types of non-infectious uveitis. Aqueous and serum samples collected from 24 patients with Fuchs uveitis, 21 patients with non-infectious uveitis, and 27 healthy subjects undergoing elective cataract surgery (control group) were analysed. In addition, vitreous samples, collected from seven uveitis patients (five Fuchs and two panuveitis) during retinal surgery, were examined. Specific immunoglobulin G antibodies against cytomegalovirus (CMV), rubella virus, herpes simplex virus (HSV), and varicella zoster virus (VZV) were investigated, and Goldmann–Witmer coefficients (GWCs) were calculated. Real-time PCR was performed to detect viral genome for HSV, VZV, and CMV, while nested PCR was conducted to detect rubella RNA. None of the control samples tested positive for any of the viral antibodies investigated. Intraocular antibody production was found in eight samples of patients affected by Fuchs uveitis (6/8 positive for rubella virus and 2/8 positive for herpes virus). Among patients with non-infectious uveitis, three tested positive for intraocular antibody production (one RV, one HSV and one for VZV). PCR was positive for RV in two patients with Fuchs uveitis, in three patients with non-infectious uveitis (one for RV and two for HSV), and in three control subjects (one for CMV and one for HSV). Our series confirmed the presence of specific viral antibodies, especially against rubella virus, in the subgroup of patients affected by Fuchs uveitis, suggesting that this virus may be responsible for this chronic inflammatory condition. Rubella virus is probably the main causative agent of Fuchs uveitis, but other viruses may also be involved in the pathogenesis of this disease.

Objectives There is increasing evidence that microRNAs (miRNAs) are deregulated in autoimmune and cardiovascular diseases. The present study aimed to identify if miRNAs are deregulated in giant cell arteritis (GCA), a vasculitis affecting large-sized and medium-sized arteries, and to determine if miRNA levels might allow to discriminate between patients with GCA and those without. Methods 58 patients who had temporal artery biopsy (TAB) for suspected GCA were included in the study and divided into three groups: patients with TAB-positive GCA showing a transmural inflammation (n=27), patients with TAB-negative GCA (n=8) and TAB-negative non-GCA patients with a final diagnosis different from GCA (n=23). To identify candidate miRNAs deregulated in GCA, we profiled the expression of 1209 miRNAs in inflamed TABs and normal TABs. Selected miRNAs were then validated by real-time PCRs and in situ hybridisation (ISH). Results MiR-146b-5p, -146a, -155, -150, -21 and -299-5p were significantly more expressed in inflamed TABs from patients with GCA. miRNAs were mainly deregulated at the tissue level because peripheral blood mononuclear cells and polymorphonuclear cells from the three groups of patients and age-matched healthy controls had similar levels of miRNAs. ISH showed that miR-21 was mainly expressed by cells in the medial and intimal layers of inflamed TABs. Patients with TAB-negative GCA had a miRNA profile similar to TAB-negative non-GCA patients. Conclusions MiR-146b-5p, -146a, -21, -150, -155, -299-5p are overexpressed in the presence of inflammation in TABs from patients with GCA.

We report 2 cases of Geotrichum capitatum infection in leukemia patients for which Aspergillus galactomannan (GM) assay was positive. The diagnostic options of G. capitatum infections in hematologic patients were reviewed. Although the pathogen was isolated from blood in 77% of cases, diagnostic difficulties remain and GM assay may have a role.

Background Recent studies found an high prevalence of varicella-zoster virus (VZV) infection in temporal arteries (TAs) from both temporal artery biopsy (TAB)-positive and TAB-negative giant cell arteritis (GCA) patients compared to controls, suggesting that VZV infection may trigger the inflammatory cascade that characterizes GCA (1,2). Objectives To analyze VZV infection in TAs from patients with TAB-positive GCA (biopsy-proven GCA), TAB-negative GCA (patients with negative TAB and a final diagnosis of GCA) and controls (patients with negative TAB and a final diagnosis different from GCA). Methods A total of 75 formalin-fixed, paraffin-embedded (FFPE) TABs performed between 2009 and 2012 at a single institution from 30 TAB-positive GCA patients, 15 TAB-negative GCA patients and 30 controls were retrieved. Six 5-μm sections of all FFPE TABs were cut. The first section was analyzed by immunohistochemistry using mouse monoclonal anti-VZVgE IgG1 antibody (Santa Cruz Biotechnology) and OptiView DAB Detection Kit (Ventana, Roche). DNA was extracted from the remaining 5 sections with the QIAamp DNA FFPE tissue kit (Qiagen) and analyzed by real-time polymerase chain reaction for the presence of VZV DNA (VZV ELITe MGB kit, ELITechGroup). In addition DNA was extracted with the RNA/DNA/Protein purification kit (Norgen Biotek) from 5 positive TABs of 2 mm length obtained from GCA patients and immediately stored frozen at -80°C. Beta globin (included in the VZV ELITe MGB kit) and a short intergenic region were amplified to verify the quality of DNA. Results 60/75 (80%) patients were female. Mean (± SD) age at TAB was 72.1 (± 8.3) years. There were no significant differences in sex and age distributions between TAB-positive GCA, TAB-negative GCA and controls. Median (Q1, Q3) time from symptoms onset to TAB was 11 (5.5, 19.3) weeks for TAB-positive GCA, 15 (9, 20) weeks for TAB-negative GCA and 12 (6, 41.6) weeks for controls, p=0.414. 22/30 (73.3%) TAB-positive GCA, 8/15 (53.3%) TAB-negative GCA and 20/30 (66.7%) controls were receiving prednisone at the time TAB was performed, p=0.407. Immunohistochemical analysis detected VZV antigen in 1/30 TAB-positive GCA, 0/15 TAB-negative GCA and 0/30 controls, p=0.467. DNA obtained from all TABs was amplifiable. DNA obtained from frozen TABs was more concentrated than that obtained from FFPE TABs which allowed to load a higher quantity of DNA per reaction increasing assay sensitivity.VZV DNA was not found in any of the FFPE TABs as well as in frozen TABs but was clearly detected in FFPE skin lesions from patients with active infection (threshold cycle for VZV DNA =26 when 0.5 ng of DNA were amplified). Conclusions Our data do not support a role for VZV infections in the etiopathogenesis of GCA. References Gilden D, et al. Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis. Neurology. 2015 May 12;84(19):1948–55. Nagel MA, et al. Analysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis. JAMA Neurol. 2015 Nov 1;72(11):1281–7. Disclosure of Interest None declared

A chemiluminescent test for anti treponemal total antibodies, Liaison Treponema Screen test (LTS), was compared with Treponema Pallidum Particle Agglutination assay (TPPA) against 1022 regular blood donors and 2627 in-and-outpatients attending the laboratories of five hospitals. All positive and doubtful tests were confirmed by Western Blot (WB) and we have discussed the criteria of WB positivity. The results for blood donors were: nonreactive 1022 TPPA and 1021 LTS and doubtful 1 LTS (WB negative) with a concordance of 99.9%.The mean and median index values of the LTS tests (0.175 and 0.15 respectively) were much lower than the doubtful and positive cut-off index values (0.9 and 1.1 respectively).The results for the 2627 patients were: 2423 (92.2%) LTS and TPPA non reactive; 191 (7.3%) LTS and TPPA reactive; 13 (0.5%) LTS and TPPA discordant. Of the 13 patients with discordant tests (1 TPPA reactive vs. LTS nonreactive and 12 LTS reactive or doubtful vs. TPPA nonreactive) 1 was true positive (LTS reactive and TPPA nonreactive), 10 true negative (LTS reactive/doubtful and TPPA nonreactive) and 2 not verifiable. The sensitivity and specificity of LTS were 99.5% and 99.6% respectively; the sensitivity and specificity of TPPA were 99.0% and 100% respectively. In conclusion, LTS and TPPA are similar in sensitivity and specificity, but an automated analyzer as Liaison is more useful than TPPA in laboratories with high workload in syphilis screening.

Aim The presence of specific auto-antibodies in serum (i.e., antinuclear antibodies or ANA, anti-extractable nuclear antigens or anti-ENA, and anti-double stranded DNA or anti-dsDNA ) is one of the major criteria in the diagnostics of Autoimmune Rheumatic Disease. As such, the request for these tests has grown exponentially in laboratory practice. The aim of this study is to describe the implementation of a joint laboratory-clinics guideline for reducing clinically inappropriate requests for autoantibody testing in a broad geographic area (Parma, Modena, Piacenza, Reggio-Emilia) for the diagnosis of Autoimmune Rheumatic Disease. Methods This study, supported by a Regional grant for innovative research projects started in January 2008, is an observational research aimed at comparing the number of ANA, anti-dsDNA and anti-ENA testing as well as the percentage of positive test results before and after implementation of the diagnostic algorithm in hospitalized patients. A multidisciplinary team consisting of clinical immunologist and laboratory scientists was established, with the aim of collecting and analysing diagnostic criteria, clinical needs, laboratory report formats, analytical procedures, as well as the number of tests performed. The laboratory results and the clinical protocol were both validated by data emerging from the clinical follow-up studies. Results A joint guideline for auto-antibody testing, placing ANA test at the first level, has been developed and implemented since January 2009. The results for the period January–June 2009 (12,738 tests) were compared with those of the same period in 2008 (13,067 tests). A significant reduction in the number of anti-dsDNA (− 26%) and anti-ENA (− 15%) was observed. The percentage of second-level tests positivity after implementation of the diagnostic protocol had also consistently increased for both ENA (13% vs 17%) and dsDNA (9% vs 11%). Discussion The development and implementation of algorithms for the diagnostics of Autoimmune Rheumatic Disease in hospitalized patients was associated with a reduction in the number of second-level tests, but also with an increased diagnostic specificity. This outcome attests that close collaboration and audit between clinicians, laboratory specialists and healthcare services is effective to develop efficient diagnostic algorithms for both hospitalized patients and outpatients.

Uveitis is a complex intraocular inflammatory disease resulting from several aetiological entities that are linked to geographical, genetic and socioeconomic variables. The purpose of this study was to provide an overview of the distribution patterns of uveitis as seen in a nationwide referral centre at a community hospital in Reggio Emilia, northern Italy, and to compare our data with those reported in previously published international series. The records of 1064 patients of Italian origin with uveitis referred to the Immunology Ocular Unit of the Arcispedale S. Maria Nuova Hospital in Reggio Emilia from 2002 to 2008 were classified and analysed. Data regarding sex, race, residence, age at presentation and at onset of uveitis, ocular involvement, clinical characteristics, ocular condition, and systemic disease associations were collected. The mean age at onset of uveitis was 41 years (range: 1–94), and the male-to-female ratio was 1:1.2. Anterior uveitis was the most common location (51.2%), followed by posterior uveitis (23.4%), panuveitis (19.6%), and intermediate uveitis (5.8%). The most frequent entities included Fuchs uveitis (22.7%), herpetic anterior uveitis (9.9%), toxoplasmosis (6.9%), HLA-B27-associated anterior uveitis (5.3%), and Behcet’s disease (5.3%). The distribution we observed of the most common disease entities conformed to previous international series. In our series, Fuchs uveitis represented the most common diagnosis (22.7%, 45% of anterior uveitis). The high percentage of specific diagnosis (74%) can be explained by the establishment of new disease categories over time as well as by a systematic multi-disciplinary diagnostic approach.

To the Editor: We report a case of pandemic (H1N1) 2009 infection in a man with serologic evidence of HIV-1 infection. The clinical course was complicated by lung and brain involvement (respiratory failure and lethargy), severe leukopenia, and thrombocytopenia, but complications resolved after treatment with oseltamivir (150 mg 2×/d). In November 2009, a 47-year-old man who had received a diagnosis of hepatitis C infection 8 months earlier sought treatment at Ospedale Santa Maria Nuova, Reggio Emilia, Italy. He had a 3-day history of fever, dry cough, and drowsiness. Eight days before being admitted, the man had resided in the hospital’s inpatient detoxification unit, in which at least 10 influenza-like cases had been recorded. While in the detoxification unit, he had received methadone, 50 mg 1×/d. Computed tomography images of the brain and radiographs of the chest were normal; ultrasound examination showed upper lobe consolidation of the left lung. Hematochemistry showed high creatine phosphokinase levels, leukocyte count of 1,380 cells/mm3 (reference range 4,000–10,000 cells/mm3), thrombocyte count of 34,000 cells/mm3 (reference range 150,000–450,000 cells/mm3), partial pressure of oxygen 56 mm Hg, and partial pressure of carbon dioxide 53 mm Hg. Urinalysis results were negative for heroin, cocaine, and alcohol; cerebrospinal fluid (CSF) analysis results were within normal limits. Thrombocyte count returned to reference range after 2 days, and leukocyte count improved but remained 6 million copies/mL, CD4 lymphocytes 51% (reference range 29%–59%). Reverse transcription–PCR for influenza subtype H1N1 performed 2 months later on a stored CSF sample gave a negative result; PCR for HIV of the same sample indicated 25,000 copies/mL. In mid-December, because of a further drop in CD4 lymphocytes to 17% (214 cells/mm3) and blood HIV RNA of 2.8 million copies/mL, the patient started highly active antiretroviral therapy and is being followed up as an outpatient. Influenza (H1N1) and primary HIV infection share many signs and symptoms, such as fever, cough, sore throat, joint or limb pain, and diarrhea. The infections also share uncommon complications of the central nervous system (CNS); e.g., drowsiness, coma, and seizures. We cannot confirm that CNS involvement in the patient reported here was caused primarily by pandemic (H1N1) 2009, as suggested by influenza-like symptoms and the apparent effect of oseltamivir. Nor can we attribute CNS involvement to primary infection with HIV-1 (1); CSF results within normal limits and PCR negative for influenza subtype H1N1 do not rule out a causal relationship with pandemic (H1N1) 2009. In fact, the few cases of pandemic (H1N1) 2009 encephalopathy described show similar characteristics among children and adults (2–4). Alternatively, some authors have attributed HIV in CSF to brain inflammation and damage (5,6). The severe leukocytopenia and thrombocytopenia in our patient have not been described, even in complicated influenza subtype H1N1 infections (7). Because lymphopenia and mild thrombocytopenia are the usual findings, we believe that they probably resulted from HIV-1 or the effect of both viruses. HIV seroconversion may initially occur during an acute febrile illness resembling influenza, and CNS involvement can complicate both infections. During an epidemic, acute HIV infection should also be considered (8). Less frequently, as in the patient described above, the 2 infections can occur simultaneously. History of recent risk behavior for blood exposure and severe leukocytopenia and thrombocytopenia should alert clinicians to other causes and prompt them to offer an HIV test to the patient.