Multisensory Stimulation Improves Cognition and Behavior in Adult Male Rats Born to LT4-treated Thyroidectomized Dams.

Gestational hypothyroidism can impair development, cognition, and mood. Here, we tested whether multisensory stimulation (MS) improves the phenotype of rats born to surgically thyroidectomized (Tx) dams suboptimally treated with LT4. 8-week-old female Tx Wistar rats were kept on daily LT4 (0.7 µg/100 g body weight) dosed by gavage (serum TSH and T4 levels indicated moderate hypothyroidism) and 3 weeks later placed for breeding. MS of the litter started at age 60 days and lasted for 8 weeks. It consisted of twice per week of physical, cognitive, sensorial, and food stimuli. The offspring were assessed before and after MS for standardized tests of locomotor activity, cognition, and mood. Gestational hypothyroidism resulted in reduced litter size and increased offspring mortality. The pups exhibited delayed physical development, impairment of short- and long-term memory, and anxiety- and depressive-like behaviors. Nonetheless, ambulatory activity, social memory, and social preference were not affected by gestational hypothyroidism. MS restored short-term memory and anxiety while improving depressive like-behaviors. MS did not improve long-term memory. MS also did not modify the performance of control litter born to intact dams. We conclude that cognition and mood impairments caused by moderate gestational hypothyroidism were reversed or minimized in rats through MS. Further studies should define the molecular mechanisms involved.

Age Worsens the Cognitive Phenotype in Mice Carrying the Thr92Ala-DIO2 Polymorphism.

The Thr92Ala-Dio2 polymorphism has been associated with reduced cognition in 2-month-old male mice and increased risk for cognitive impairment and Alzheimer's disease in African Americans. This has been attributed to reduced thyroid hormone (TH) signaling and endoplasmic reticulum (ER) stress in the brain. Here we studied the Thr92Ala-Dio2 mouse model and saw that older male mice (7-8-month-old) exhibited a more severe cognition impairment, which extended to different aspects of declarative and working memories. A similar phenotype was observed in 4-5-month-old female mice. There were no structural alterations in the prefrontal cortex (PFC) and hippocampus of the Thr92Ala-Dio2 mouse. Nonetheless, in both male and female PFC, there was an enrichment in genes associated with TH-dependent processes, ER stress, and Golgi apparatus, while in the hippocampus there was additional enrichment in genes associated with inflammation and apoptosis. Reduced TH signaling remains a key mechanism of disease given that short-term treatment with L-T3 rescued the cognitive phenotype observed in males and females. We conclude that in mice, age is an additional risk factor for cognitive impairment associated with the Thr92Ala-Dio2 polymorphism. In addition to reduced TH signaling, ER-stress, and involvement of the Golgi apparatus, hippocampal inflammation and apoptosis were identified as potentially important mechanisms of a disease.

rumAB genes from SXT/R391 ICEs confer UV-induced mutability to Proteus mirabilis hosts and improve conjugation after UV irradiation.

Proteus mirabilis is one of the Enterobacteriales species that has been deemed as non-mutable by DNA damaging agents. A genomic analysis of P. mirabilis genomes shows that this species often does not carry pol V-encoding genes in its chromosome, which are responsible for SOS mutagenesis in other bacteria. On the other hand, the highly active umuDC homologs rumAB are carried in the mobile integrative conjugative elements (ICEs) from the SXT/R391 family that are frequently found in this species. Here we show that isolates devoid of SXT/R391 are indeed weakly or non-mutable by UV-light exposure, in contrast to isolates carrying SXT/R391 elements, some of which are mutable under these conditions. SXT/R391-bearing isolates display a variable behavior regarding UV-induced mutagenesis, despite the functionality of rumAB homologs carried by them. We also show that the globally dispersed ICEPmiJpn1 confers UV mutability to otherwise non-mutable isolates and demonstrate that this phenomenon is dependent on rumAB genes. Finally, we investigated whether rumAB genes could play a role in the conjugation of ICEPmiJpn1 and found that these genes improve the conjugation of SXT/R391 by a small margin. Taken together, these results show that the presence of rumAB in SXT/R391 ICEs endows the hosts with damage-inducible mutagenesis ability and promotes a small but significant enhancement in element transfer after exposure to UV light.

Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in patients with juvenile dermatomyositis: a real-world multicentre study.

BACKGROUND: Concerns about the safety and efficacy of vaccines in patients with autoimmune diseases (AID) have led to contradictions and low vaccination coverage in this population, who are at a higher risk of infections, including by human papillomavirus (HPV). Although HPV vaccines have been recommended for immunocompromised patients, there is still a lack of data to support its use for AID patients, such as juvenile dermatomyositis (JDM) patients. The aim of this study was to assess the safety and immunogenicity of the quadrivalent HPV (qHPV) vaccine in a cohort of JDM patients. METHODS: JDM patients aged from 9 to 20 years and healthy controls (HC) were enrolled to receive a 3-dose schedule of qHPV vaccine from March/2014 to March/2016. Study visits were performed before the first dose, 1 month after the second and third doses, and 6 months after the third dose. Participants completed a diary of possible adverse events for 14 days following each dose of vaccination (AEFV). Disease activity and current therapy were analyzed at each visit for JDM patients. In addition, serum samples from all participants were collected to test antibody concentrations against HPV16 and 18 at each visit. Participant recruitment was conducted in ten Brazilian centres. From 47 eligible JDM patients and 41 HC, 42 and 35, respectively, completed the 3-dose schedule of the vaccine, given that five JDM patients and two HC had received doses prior to their inclusion in the study. RESULTS: The AEFVs presented by the participants were mild and in general did not differ between JDM and HC groups. No severe AEFVs were related to the vaccination. Disease activity was stable, or even improved during the follow-up. One month after the third dose of the vaccine the JDM group presented seropositivity of 100% for HPV16 and 97% for HPV18, similarly to the HC group, who presented 100% for both serotypes (p = 1.000). Six months after the third dose the seropositivity for the patient group was 94% for both HPV types. CONCLUSIONS: The HPV vaccination in this cohort of JDM patients was safe and immunogenic. Since the seropositivity against HPV16 and 18 was very high after the 3-dose schedule, this regimen should be recommended for JDM patients. TRIAL REGISTRATION: Brazilian Clinical Trials Registry, number: RBR-9ypbtf . Registered 20 March 2018 - Retrospectively registered.

Genomic Analysis of SXT/R391 Integrative Conjugative Elements From Proteus mirabilis Isolated in Brazil.

Integrative conjugative elements (ICEs) are widespread in many bacterial species, often carrying antibiotic resistance determinants. In the present work, we screened a collection of Proteus mirabilis clinical isolates for the presence of type 1 SXT/R391 ICEs. Among the 76 isolates analyzed, 5 of them carry such elements. The complete sequences of these elements were obtained. One of the isolates carried the CMY-2 beta-lactamase gene in a transposon and is nearly identical to the element ICEPmiJpn1 previously described in Japan, and later shown to be present in other parts of the world, indicating global spread of this element. Nevertheless, the Brazilian isolate carrying ICEPmiJpn1 is not clonally related to the other lineages carrying the same element around the world. The other ICEs identified in this work do not carry known antibiotic resistance markers and are diverse in variable gene content and size, suggesting that these elements may be responsible for the acquisition of other advantageous traits by bacteria. Some sequences carried by these elements in Brazilian strains were not previously found in other SXT/R391 variants.

Panniculitis in childhood-onset systemic lupus erythematosus: a multicentric cohort study.

OBJECTIVE: To evaluate prevalence, clinical manifestations, laboratory abnormalities, treatment and outcome in a multicenter cohort of childhood-onset systemic lupus erythematosus (cSLE) patients with and without panniculitis. METHODS: Panniculitis was diagnosed due to painful subcutaneous nodules and/or plaques in deep dermis/subcutaneous tissues and lobular/mixed panniculitis with lymphocytic lobular inflammatory infiltrate in skin biopsy. Statistical analysis was performed using Bonferroni correction(p < 0.004). RESULTS: Panniculitis was observed in 6/847(0.7%) cSLE. Painful subcutaneous erythematosus and indurated nodules were observed in 6/6 panniculitis patients and painful subcutaneous plaques in 4/6. Generalized distribution was evidenced in 3/6 and localized in upper limbs in 2/6 and face in 1/6. Cutaneous hyperpigmentation and/or cutaneous atrophy occurred in 5/6. Histopathology features showed lobular panniculitis without vasculitis in 5/6(one of them had concomitant obliterative vasculopathy due to antiphospholipid syndrome) and panniculitis with vasculitis in 1/6. Comparison between cSLE with panniculitis and 60 cSLE without panniculitis with same disease duration [2.75(0-11.4) vs. 2.83(0-11.8) years,p = 0.297], showed higher frequencies of constitutional involvement (67% vs. 10%,p = 0.003) and leukopenia (67% vs. 7%,p = 0.002). Cutaneous atrophy and hyperpigmentation occurred in 83% of patients. CONCLUSIONS: Panniculitis is a rare skin manifestation of cSLE occurring in the first three years of disease with considerable sequelae. The majority of patients have concomitant mild lupus manifestations.

Panniculitis in childhood-onset systemic lupus erythematosus: a multicentric cohort study

Abstract Objective: To evaluate prevalence, clinical manifestations, laboratory abnormalities, treatment and outcome in a multicenter cohort of childhood-onset systemic lupus erythematosus (cSLE) patients with and without panniculitis. Methods: Panniculitis was diagnosed due to painful subcutaneous nodules and/or plaques in deep dermis/subcutaneous tissues and lobular/mixed panniculitis with lymphocytic lobular inflammatory infiltrate in skin biopsy. Statistical analysis was performed using Bonferroni correction(p < 0.004). Results: Panniculitis was observed in 6/847(0.7%) cSLE. Painful subcutaneous erythematosus and indurated nodules were observed in 6/6 panniculitis patients and painful subcutaneous plaques in 4/6. Generalized distribution was evidenced in 3/6 and localized in upper limbs in 2/6 and face in 1/6. Cutaneous hyperpigmentation and/or cutaneous atrophy occurred in 5/6. Histopathology features showed lobular panniculitis without vasculitis in 5/6(one of them had concomitant obliterative vasculopathy due to antiphospholipid syndrome) and panniculitis with vasculitis in 1/6. Comparison between cSLE with panniculitis and 60 cSLE without panniculitis with same disease duration [2.75(0-11.4) vs. 2.83(0-11.8) years,p = 0.297], showed higher frequencies of constitutional involvement (67% vs. 10%,p = 0.003) and leukopenia (67% vs. 7%,p = 0.002). Cutaneous atrophy and hyperpigmentation occurred in 83% of patients. Conclusions: Panniculitis is a rare skin manifestation of cSLE occurring in the first three years of disease with considerable sequelae. The majority of patients have concomitant mild lupus manifestations.

The Brazilian Portuguese version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Brazilian Portuguese language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 231 JIA patients (14.7% systemic, 43.3% oligoarticular, 22.5% RF negative polyarthritis, 19.5% other categories) and 72 healthy children, were enrolled in three centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Brazilian Portuguese version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Increased mutability to fosfomycin resistance in Proteus mirabilis clinical isolates.

In the present study, we screened a collection of 77 Proteus mirabilis clinical isolates for the presence of mutators, using the frequency of both rifampicin and fosfomycin resistance mutants as markers of spontaneous mutagenesis. We found that none of the strains in our collection are mutators for the rifampicin resistance (RifR) marker. Nevertheless, a significant fraction of the isolates (17%) show high frequencies of fosfomycin resistant mutants (FosR). We show that this increased mutability to FosR correlates with a low level of resistance to Fosfomycin (MICs 8-64µg/ml). These strains also show high frequencies of single step mutants with clinically relevant FosR resistance levels (MIC ≥256µg/ml). Our findings point out to the risk of fosfomycin resistance emergence in P. mirabilis.

Systematic studies of the interactions between a model polyphenol compound and microbial ß-glucosidases.

Lignin is a major obstacle for cost-effective conversion of cellulose into fermentable sugars. Non-productive adsorption onto insoluble lignin fragments and interactions with soluble phenols are important inhibition mechanisms of cellulases, including ß-glucosidases. Here, we examined the inhibitory effect of tannic acid (TAN), a model polyphenolic compound, on ß-glucosidases from the bacterium Thermotoga petrophila (TpBGL1 and TpBGL3) and archaeon Pyrococcus furiosus (PfBGL1). The results revealed that the inhibition effects on ß-glucosidases were TAN concentration-dependent. TpBGL1 and TpBGL3 were more tolerant to the presence of TAN when compared with PfBGL1, while TpBGL1 was less inhibited when compared with TpBGL3. In an attempt to better understand the inhibitory effect, the interaction between TAN and ß-glucosidases were analyzed by isothermal titration calorimetry (ITC). Furthermore, the exposed hydrophobic surface areas in ß-glucosidases were analyzed using a fluorescent probe and compared with the results of inhibition and ITC. The binding constants determined by ITC for the interactions between TAN and ß-glucosidases presented the same order of magnitude. However, the number of binding sites and exposed hydrophobic surface areas varied for the ß-glucosidases studied. The binding between TAN and ß-glucosidases were driven by enthalpic effects and with an unfavorable negative change in entropy upon binding. Furthermore, the data suggest that there is a high correlation between exposed hydrophobic surface areas and the number of binding sites on the inhibition of microbial ß-glucosidases by TAN. These studies can be useful for biotechnological applications.

Photobiosynthesis of stable and functional silver/silver chloride nanoparticles with hydrolytic activity using hyperthermophilic ß-glucosidases with industrial potential.

The ß-glucosidases are important enzymes employed in a large number of processes and industrial applications, including biofuel production from biomass. Therefore, in this study, we reported for the first time the photobiosynthesis of stable and functional silver/silver chloride nanoparticles (Ag/AgCl-NPs) using two hyperthermostable bacterial ß-glucosidases with industrial potential. The syntheses were straightforward and rapid processes carried out by mixing ß-glucosidase and silver nitrate (in buffer 10mM Tris-HCl, pH 8) under irradiation with light (over a wavelength range of 450-600nm), therefore, compatible with the green chemistry procedure. Synthesized Ag/AgCl-NPs were characterized using a series of physical techniques. Absorption spectroscopy showed a strong absorption band centered at 460nm due to surface plasmon resonance of the Ag-NPs. X-ray diffraction analysis revealed that the Ag/AgCl-NPs were purely crystalline in nature. Under electron microscopy, Ag/AgCl-NPs of variable diameter ranging from 10 to 100nm can be visualized. Furthermore, electron microscopy, zeta potential and Fourier transform infrared spectroscopy results confirmed the presence of ß-glucosidases coating and stabilizing the Ag/AgCl-NPs. Finally, the results showed that the enzymatic activities were maintained in the ß-glucosidases assisted Ag/AgCl-NPs. The information described here should provide a useful basis for future studies of ß-glucosidases assisted Ag/AgCl-NPs, including biotechnological applications.

Health related quality of life measure in systemic pediatric rheumatic diseases and its translation to different languages: an international collaboration.

BACKGROUND: Rheumatic diseases in children are associated with significant morbidity and poor health-related quality of life (HRQOL). There is no health-related quality of life (HRQOL) scale available specifically for children with less common rheumatic diseases. These diseases share several features with systemic lupus erythematosus (SLE) such as their chronic episodic nature, multi-systemic involvement, and the need for immunosuppressive medications. HRQOL scale developed for pediatric SLE will likely be applicable to children with systemic inflammatory diseases. FINDINGS: We adapted Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY©) to Simple Measure of Impact of Illness in Youngsters (SMILY©-Illness) and had it reviewed by pediatric rheumatologists for its appropriateness and cultural suitability. We tested SMILY©-Illness in patients with inflammatory rheumatic diseases and then translated it into 28 languages. Nineteen children (79% female, n=15) and 17 parents participated. The mean age was 12±4 years, with median disease duration of 21 months (1-172 months). We translated SMILY©-Illness into the following 28 languages: Danish, Dutch, French (France), English (UK), German (Germany), German (Austria), German (Switzerland), Hebrew, Italian, Portuguese (Brazil), Slovene, Spanish (USA and Puerto Rico), Spanish (Spain), Spanish (Argentina), Spanish (Mexico), Spanish (Venezuela), Turkish, Afrikaans, Arabic (Saudi Arabia), Arabic (Egypt), Czech, Greek, Hindi, Hungarian, Japanese, Romanian, Serbian and Xhosa. CONCLUSION: SMILY©-Illness is a brief, easy to administer and score HRQOL scale for children with systemic rheumatic diseases. It is suitable for use across different age groups and literacy levels. SMILY©-Illness with its available translations may be used as useful adjuncts to clinical practice and research.

Frequency of radiographic damage and progression in individual joints in children with juvenile idiopathic arthritis.

OBJECTIVE: To evaluate the presence and progression of radiographic joint damage, as assessed with the adapted Sharp/van der Heijde score (SHS), in individual joints in the hand and wrist in patients with juvenile idiopathic arthritis (JIA) and to compare progression of damage among different JIA categories. METHODS: A total of 372 radiographs of both wrists and hands obtained at first observation and at last followup visit (after 1-10 years) in 186 children with polyarticular-course JIA were evaluated. All radiographs were scored using the adapted SHS by 2 independent readers. Radiographic assessment included evaluation of joint space narrowing (JSN) and erosions on baseline and last followup radiographs and of progression of radiographic changes from baseline to last followup radiographs. RESULTS: Both JSN and erosions occurred in all adapted SHS areas. Overall, radiographic damage and progression were more common in the wrist and less common in metacarpophalangeal (MCP) joints. The hamate and capitate areas appeared particularly vulnerable to cartilage loss. Erosions were identified most frequently in the hamate and capitate bones as well as in the second and third metacarpal bases. Patients with extended oligoarthritis were distinctly less susceptible to JSN in hand joints, whereas patients with polyarthritis showed a greater tendency to developing erosions in hand joints. CONCLUSION: Radiographic joint damage and progression in our patients with JIA were seen most commonly in the wrist and less commonly in MCP joints. The frequency and localization of structural abnormalities differed markedly across disease categories.

Profile of paediatric rheumatology specialists and services in the state of São Paulo.

INTRODUCTION: Paediatric rheumatology (PR) is an emerging specialty, practised by a limited number of specialists. Currently, there is neither a record of the profile of rheumatology patients being treated in Brazil nor data on the training of qualified rheumatology professionals in the country. OBJECTIVE: To investigate the profile of PR specialists and services, as well as the characteristics of paediatric patients with rheumatic diseases, for estimating the current state of rheumatology in the state of São Paulo. PATIENTS AND METHODS: In 2010, the scientific department of PR of the Paediatric Society of São Paulo administered a questionnaire that was answered by 24/31 accredited specialists in PR practising in state of São Paulo and by 8/21 institutions that provide PR care. RESULTS: Most (91%) of the surveyed professionals practise in public institutions. Private clinics (28.6%) and public institutions (37.5%) reported not having access to nailfold capillaroscopy, and 50% of the private clinics reported not having access to acupuncture. The average duration of professional practise in PR was 9.4 years, and 67% of the physicians had attended postgraduate programmes. Seven (87.5%) public institutions perform teaching activities, in which new paediatric rheumatologists are trained, and five (62.5%) offer postgraduate programmes. Two-thirds of the surveyed specialists use immunosuppressants and biological agents classified as "restricted use" by the Health Secretariat. The disease most frequently reported was juvenile idiopathic arthritis (29.1-34.5%), followed by juvenile systemic lupus erythematosus (JSLE) (11.6-12.3%) and rheumatic fever (9.1-15.9%). The incidence of vasculitis (including Henoch-Schönlein purpura, Wegener's granulomatosis, and Takayasu's arteritis) and autoinflammatory syndromes was higher in public institutions compared to other institutions (P = 0.03, P = 0.04, P = 0.002, and P < 0.0001, respectively). Patients with JSLE had the highest mortality rate (68% of deaths), mainly due to infection. CONCLUSION: The field of PR in the state of São Paulo has a significant number of specialists with postgraduate degrees who mostly practise at teaching institutions with infrastructures appropriate for the care of high-complexity patients.

Eficiência do tratamento da Classe II subdivisão com braquetes autoligáveis / Efficiency of class II subdivision treatment with self-ligating brackets

O objetivo desse trabalho é apresentar o tratamento de uma má oclusão de Classe II subdivisão com a utilização de braquetes autoligáveis, apontando a eficiência e a otimização do tratamento ortodôntico com esse sistema. Foram utilizados braquetes autoligáveis Speed (Strite), prescrição Roth, slot de 0,022" e fios preconizados pelo fabricante. A paciente adulta apresentava discrepância anteroposterior de ½ Classe II, divisão 1, subdivisão direita, com desvio das linhas médias dentárias superior e inferior e diastemas entre incisivos e caninos inferiores. Após quatorze meses de tratamento ortodôntico, observou-se a correção dos problemas oclusais descritos inicialmente. As alterações ocorridas com o tratamento foram puramente de natureza dentária: inclinação dos incisivos inferiores para vestibular, inclinação dos molares superiores para distal e dos molares inferiores para mesial, fechamento dos diastemas e correção dos desvios das linhas médias dentárias. Em relação ao curto tempo de tratamento, entende-se que, por apresentar menor atrito durante a mecânica ortodôntica, o sistema autoligável empregado possa ter influenciado na eficiência e no sucesso do tratamento. Concluiu-se que o tratamento foi eficientemente realizado, evidenciado pelo curto período de tempo com que todos os problemas oclusais iniciais foram resolvidos.

Perfil de especialistas e de serviços em reumatologia pediátrica no estado de São Paulo / Profile of paediatric rheumatology specialists and services in the state of São Paulo

INTRODUÇÃO: A reumatologia pediátrica (RP) é uma especialidade emergente, com número restrito de especialistas, e ainda não conta com uma casuística brasileira sobre o perfil dos pacientes atendidos e as informações sobre a formação de profissionais capacitados. OBJETIVO: Estudar o perfil dos especialistas e dos serviços em RP e as características dos pacientes com doenças reumáticas nessa faixa etária a fim de estimar a situação atual no estado de São Paulo (ESP). PACIENTES E MÉTODOS: No ano de 2010 o departamento científico de RP da Sociedade de Pediatria de São Paulo encaminhou um questionário respondido por 24/31 especialistas com título de especialização em RP que atuam no ESP e por 8/12 instituições com atendimento nesta especialidade. RESULTADOS: A maioria (91%) dos profissionais exerce suas atividades em instituições públicas. Clínicas privadas (28,6%) e instituições (37,5%) relataram não ter acesso ao exame de capilaroscopia e 50% das clínicas privadas não tem acesso à acupuntura. A média de tempo de prática profissional na especialidade foi de 9,4 anos, sendo 67% deles pós-graduados. Sete (87,5%) instituições públicas atuam na área de ensino, formando novos reumatologistas pediátricos. Cinco (62,5%) delas têm pós-graduação. Dois terços dos especialistas utilizam imunossupressores e agentes biológicos de uso restrito pela Secretaria da Saúde. A doença mais atendida foi artrite idiopática juvenil (29,1%-34,5%), seguida de lúpus eritematoso sistêmico juvenil (LESJ) (11,6%-12,3%) e febre reumática (9,1%-15,9%). Vasculites (púrpura de Henoch Schönlein, Wegener, Takayasu) e síndromes autoinflamatórias foram mais incidentes nas instituições públicas (P = 0,03; P = 0,04; P = 0,002 e P < 0,0001, respectivamente). O LESJ foi a doença com maior mortalidade (68% dos óbitos), principalmente por infecção. CONCLUSÃO: A RP no ESP conta com um número expressivo de especialistas pós-graduados, que atuam especialmente em instituições de ensino, com infraestrutura adequada ao atendimento de pacientes de alta complexidade.

INTRODUCTION: Paediatric rheumatology (PR) is an emerging specialty, practised by a limited number of specialists. Currently, there is neither a record of the profile of rheumatology patients being treated in Brazil nor data on the training of qualified rheumatology professionals in the country. OBJECTIVE: To investigate the profile of PR specialists and services, as well as the characteristics of paediatric patients with rheumatic diseases, for estimating the current state of rheumatology in the state of São Paulo. PATIENTS AND METHODS: In 2010, the scientific department of PR of the Paediatric Society of São Paulo administered a questionnaire that was answered by 24/31 accredited specialists in PR practising in state of São Paulo and by 8/21 institutions that provide PR care. RESULTS: Most (91%) of the surveyed professionals practise in public institutions. Private clinics (28.6%) and public institutions (37.5%) reported not having access to nailfold capillaroscopy, and 50% of the private clinics reported not having access to acupuncture. The average duration of professional practise in PR was 9.4 years, and 67% of the physicians had attended postgraduate programmes. Seven (87.5%) public institutions perform teaching activities, in which new paediatric rheumatologists are trained, and five (62.5%) offer postgraduate programmes. Two-thirds of the surveyed specialists use immunosuppressants and biological agents classified as "restricted use" by the Health Secretariat. The disease most frequently reported was juvenile idiopathic arthritis (29.1-34.5%), followed by juvenile systemic lupus erythematosus (JSLE) (11.6-12.3%) and rheumatic fever (9.1-15.9%). The incidence of vasculitis (including Henoch-Schönlein purpura, Wegener's granulomatosis, and Takayasu's arteritis) and autoinflammatory syndromes was higher in public institutions compared to other institutions (P = 0.03, P = 0.04, P = 0.002, and P < 0.0001, respectively). Patients with JSLE had the highest mortality rate (68% of deaths), mainly due to infection. CONCLUSION: The field of PR in the state of São Paulo has a significant number of specialists with postgraduate degrees who mostly practise at teaching institutions with infrastructures appropriate for the care of high-complexity patients.

Avaliação clinimétrica do desfecho em uma série de casos de Lúpus Eritematoso Sistêmico Juvenil (LESJ) / Clinimetrics outcome assessment in a number of cases of juvenile systemic lupus erythematosus

Instrumentos multidimensionais quantitativos para atividade e dano têm sido utilizados para mensurar o desfecho clínico do Lúpus Eritematoso Sistêmico Juvenil (LESJ), com o objetivo de avaliar o impacto real da morbidade. Avaliar a sobrevida, o padrão de atividade da doença, o dano e o impacto no crescimento em uma coorte de LESJ. Os pacientes foram classificados pelos padrões de atividade ativo crônico (AC), recidivante-remitente (RR) e quiescente prolongado (QP) de acordo com o Modified SLEDAI-2K e ECLAM, pontuados em cada consulta e calculando-se a área sob a curva da atividade em intervalos de observação. O dano foi avaliado na última consulta pelo Pediatric SLICC/ACR Damage Index (Ped/SDI), para aqueles com acompanhamento por mais de um ano. Foi realizada análise de sobrevida considerando óbito, dano e atraso no crescimento como desfechos para a coorte e estratificada pelos padrões AC e RR. O modelo de Cox foi utilizado para identificar fatores preditivos para esses desfechos. Foram revisados 37 casos com mediana de idade ao diagnóstico de 11,2 anos e do tempo de acompanhamento de 2,7 anos. O padrão RR foi encontrado em 67,5%, AC em 29,8% e QP em 2,7%, segundo a classificação pelo Modified SLEDAI-2K. Pelo ECLAM, as frequências observadas foram 45,9%, 48,7% e 5,4%, respectivamente. A taxa de sobrevida em 5 anos foi 90%. Dano e atraso no crescimento foram observados em 62,5% e 31,3%, respectivamente. O tempo médio para o dano foi 4,8 ± 0,5 anos. A probabilidade de dano foi 10% com 1 ano, 15% com 2 anos, 32% com 3 anos e 47% com 5 anos de acompanhamento. Para o atraso no crescimento, as probabilidades foram 3%, 12%, 17% e 31% respectivamente, com tempo médio de 5,2 ± 0,4 anos. Os pacientes com padrão AC evoluem com dano mais rapidamente que aqueles com padrão RR. O dano foi associado com a duração da doença, plaquetopenia e alopecia...

Activity and damage tools have been used to measure Juvenile Systemic Lupus Erythematosus (JSLE) outcome, aiming at assessing the real impact on morbidity. Evaluate survival, disease activity patterns, damage and growth failure in a cohort of JSLE patients. Patients were classified by disease activity patterns as chronic active (CA), relapsing-remitting (RR) and long quiescent (LQ) disease course according to Modified SLEDAI-2K and ECLAM, scored at each visit and summarized by the area under curve plotted between two evaluation intervals. Damage was scored at the last visit by the Pediatric SLICC/ACR Damage Index (Ped/SDI), selecting cases followed for more than one year. Survival curves considering the events death, damage and growth failure were plotted, for the whole cohort and stratified by the CA and RR patterns. Cox model was built to identify outcome predictors. Thirty seven patients with 11.2 years median age at diagnosis and 2.7 years median follow up were reviewed. The RR pattern was found in 67.5%, CA in 29.8% and LQ in 2.7%, according to Modified SLEDAI-2K. By ECLAM, the frequencies were 45.9%, 48.7% and 5.4%, respectively. The 5-year survival rate was 90%. Damage and growth failure were observed in 62.5% and 31.3%, respectively. The mean time for damage was 4.8 ± 0.5 years. Damage probability was 10% at 1 year, 15% at 2 years, 32% at 3 years and 47% at 5 years. For growth failure, the probabilities were 3%, 12%, 17% e 31% respectively, with mean time 5.2 ± 0.4 years. Patients with the CA pattern evolved into damage faster than those with the RR pattern. Damage was associated with disease duration, thrombocytopenia and alopecia at disease onset. Growth failure associated with disease duration and renal failure at disease onset. Progression to damage was observed in nearly two thirds of patients. Damage accrual predominated in patients with the CA pattern...

Progression of articular and extraarticular damage in oligoarticular juvenile idiopathic arthritis.

OBJECTIVES: Evaluate damage in oligoarticular JIA, estimating its frequency, risks and probability over time. METHODS: A cross-sectional and retrospective analysis of Juvenile Arthritis Damage Index (JADI) scoring, with both articular and extraarticular components, active joint count, disability index by CHAQ and Steinbrocker class, physician's global assessment, child's pain and overall well-being visual analogue scale (VAS), was conducted in patients with oligoarticular JIA. Damage risk factors were estimated by univariate analysis and by generalised linear model. The probability of damage over time was estimated by survival analysis and damage progression rates were calculated by hazard function. RESULTS: Seventy-five JIA cases were assessed, 89.3% persistent and 10.7% extended oligoarthritis, with median follow-up duration 1.7 years (IQR 1.3-3.1). Damage occurred in 38.7%. JADI-A correlated moderately only with the number of limited joints (rs= 0.50, p<0.0001). Female sex (OR 3.5, 95% CI 1.0-11.6), DMARD use (OR 3.9, 95%CI 1.0-15.0) and knee involvement (OR 4.2, 95%CI 1.3-13.5) were significantly associated with joint damage, whereas only joint steroid injection was associated with extraarticular damage (OR 5.9, 95% CI 1.8-19.3). Damage probability at 5 years was 50% for JADI-A, and 57% for JADI-E. Calculated hazard rates each year were 16.1% and 16.3%, for JADI-A and JADI-E, respectively. CONCLUSIONS: Sex, DMARD use and knee involvement were associated with joint damage, whereas only joint steroid injection was associated with extraarticular damage, which progressed at stable rates over ten years.

Indications and complications of tracheostomy in children.

UNLABELLED: Indications for tracheostomy have changed and its complications are more common in children. AIM: To evaluate the indications and complications of tracheostomies performed in children. MATERIALS AND METHODS: A retrospective study with review of medical records of patients aged from 1 day to 16 years who underwent tracheostomy at a university hospital during the period of August 2000 to July 2008. We assessed data on age, gender, indications and intra and postoperative complications. RESULTS: Fifty-eight children under 16 years of age underwent tracheotomy during the study period. The mean age was 3.7 years. Airway obstruction was the main indication for surgery (n = 40; 69%). The incidence of complications in the postoperative period was 19% (11 patients), the majority happening during the late postoperative period. A further complication observed was cannula clogging. There were no complications related to the procedure during the surgery. CONCLUSION: The main indications for tracheostomy in children were airway obstruction and prolonged OTI. The most frequent postoperative complications were cannula obstruction and decannulation. The indications and complications observed were similar to those reported in the literature by other services.

Indicações e complicações de traqueostomia em crianças / Indications and complications of tracheostomy in children

Indications for tracheostomy have changed and its complications are more common in children. AIM: To evaluate the indications and complications of tracheostomies performed in children. MATERIALS AND METHODS: A retrospective study with review of medical records of patients aged from 1 day to 16 years who underwent tracheostomy at a university hospital during the period of August 2000 to July 2008. We assessed data on age, gender, indications and intra and postoperative complications. RESULTS: Fifty-eight children under 16 years of age underwent tracheotomy during the study period. The mean age was 3.7 years. Airway obstruction was the main indication for surgery (n = 40; 69 percent). The incidence of complications in the postoperative period was 19 percent (11 patients), the majority happening during the late postoperative period. A further complication observed was cannula clogging. There were no complications related to the procedure during the surgery. CONCLUSION: The main indications for tracheostomy in children were airway obstruction and prolonged OTI. The most frequent postoperative complications were cannula obstruction and decannulation. The indications and complications observed were similar to those reported in the literature by other services.

Indicação de traqueostomia passou por transformações e sua complicação são mais frequentes em crianças. OBJETIVO: Avaliar as indicações e complicações de traqueostomias realizadas em crianças. MATERIAL E MÉTODO: Estudo retrospectivo, com revisão de prontuários de pacientes com idade entre 1 dia de vida e 16 anos submetidos à traqueostomia em um hospital universitário durante o período de agosto de 2000 a julho de 2008. Foram avaliados dados referentes à idade, gênero, indicações e complicações intra e pós-operatórias. RESULTADOS: Cinquenta e oito crianças, menores de 16 anos, foram submetidas à traqueostomia durante o período estudado. A média de idade foi de 3.7 anos. Obstrução de via aérea foi a principal indicação cirúrgica (n=40; 69 por cento). A incidência de complicações no pós-operatório foi de 19 por cento (11 pacientes), sendo a maioria no pós-operatório tardio. A complicação mais observada foi obstrução de cânula. Não houve complicações inerentes ao procedimento durante o intra-operatório. CONCLUSÃO: As principais indicações de traqueostomia em crianças foram obstrução de via aérea e IOT prolongada. As complicações pós-operatórias mais frequentes foram obstrução de cânula e decanulação acidental. As indicações e complicações observadas são semelhantes às relatadas por outros serviços na literatura.