A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2)

Abstract Introduction The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. Patients and methods This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. Results Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. Conclusion The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).

Analysis of surgical and histopathological results of robot-assisted partial nephrectomy with use of three or four robotic arms: an early series results

ABSTRACT Objectives: The aim of this study was to evaluate whether criteria exist to guide election between the use the three- or four-arm technique in robotic partial nephrectomy (RPN) instead of just the surgeon's preference. Material and Methods: We performed a retrospective review of 80 patients submitted to RPN from May 2016 to February 2020. The patients were divided into two groups of 40, the first submitted to the surgical procedure with use of three robotic arms and the second with four arms. The group division was performed independently of the complexity of the cases, age or gender of the patients and laterality of the renal lesions. Peri- and postoperative data were analyzed for comparison between the two groups. Results: Both techniques had similar oncological outcomes (positive tumor margins), renal function preservation (warm ischemia time) and hemorrhagic complications (estimated blood loss and renal artery pseudoaneurysm), with a small difference in the need for blood transfusion, favoring the technique with three arms. Conclusions: The two robotic partial nephrectomy techniques had similar oncological and postoperative outcomes, with minimal perioperative complications. The three-arm technique is safe and feasible regardless of the complexity and size of the tumor. Additionally, the use of the three-arm technique reduced surgery costs by US$ 413.00 per patient.

Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): a Brazilian cohort

Abstract Background: Paediatric inflammatory multisystem syndrome (PIMS) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been described since mid-April 2020 with the first reports coming from Europe. Our objective was to describe the characteristics of patients among the Brazilian population. Methods: A multicenter retrospective study was conducted with the participation of five pediatric rheumatology centers in Brazil during the period from March to November 2020. Children and adolescents with PIMS temporally associated with SARS-CoV-2 (TS) who met the definition criteria for the disease according to the Royal College of Paediatrics and Child Health were included. Demographic, clinical, laboratory, therapeutic characteristics and molecular and serological diagnosis of SARS-CoV-2 infection were described. Results: Fifty-seven children and adolescents with PIMS-TS were evaluated, 54% female, with a median age of 8 (3-11) years. Most (86%) were previously healthy, with asthma being the main comorbidity, present in 10% of the patients. Fever was the main manifestation, present in all patients, followed by mucocutaneous and gastrointestinal features, present in 89% and 81% of the patients, respectively. Myocarditis occurred in 21% of the patients and in 68% of them required intensive care. The Kawasaki disease phenotype occurred in most patients (77%). All patients had elevated inflammatory markers, with elevated CRP being the most found (98%). Anemia and lymphopenia were present in 79% and 72%, respectively. Laboratory evidence of SARS-CoV-2 was found in 77% of the patients, with 39% positive RT-PCR and 84% positive serology for SARS-CoV-2. An immunomodulatory treatment was performed in 91% of the patients, with 67% receiving intravenous immunoglobulin (IVIG) associated with glucocorticoid, 21% receiving IVIG, and 3.5% receiving glucocorticoid. The median length of hospitalization was 10 days. Conclusions: This study showed a high morbidity of PIMS-TS in Brazilian children, with a prolonged length of hospitalization and a high rate of admission to pediatric intensive care unit. Multicenter prospective studies are needed to assess the morbidity of the disease in the medium and long term.

Findings regarding non-sexual penile fracture in a referral emergency hospital

ABSTRACT Purpose: To describe penile fracture (PF) findings with non-sexual etiology in a referral emergency hospital, with emphasis on demographic data, clinical and intraoperative findings and long-term outcomes. Materials and Methods: Patients with PF of non-sexual cause operated at our institution from January 2014 to January 2019 were submitted to surgical treatment and monitored for at least three months after surgery. Etiology of trauma, epidemiological and clinical presentation data, time to intervention and operative findings were reviewed retrospectively. The evaluation of postoperative erectile function was carried out by filling out the International Index of Erection Function - 5 (IIEF-5). The tool used to assess urinary function was the International Prostate Symptom Score (IPSS) questionnaire. Results: Of a total of 149 patients submitted to surgical treatment for PF, 18 (12%) reported non-sexual etiology. Twelve (66.6%) cases were due to penile manipulation through the act of bending the penis during morning erection, three (16.6%) when rolling over in bed with erect penis, one (5.5%) when embracing the wife during erection, one (5.5%) to laying on the partner with erect penis and the other (5.5%) when sitting on the toilet with an erection. Operative findings were unilateral corpus cavernosum injury in all cases. Only one (5.5%) patient had a partial urethral lesion. Follow-up time varied from 3 to 18 months (mean, 10.1 months). Three (16.6%) patients developed erectile dysfunction six months after surgery. However, all of them responded to treatment with IPDE-5 and reported improvement of erection, with no need for medication, on reevaluation after 18 months. One (5.5%) patient developed penile curvature < 30 degrees. Thirteen (72.2%) patients developed penile nodules. No patient presented voiding complaints during follow-up. Conclusions: PF is a rare urologic emergency, especially with the non-sexual etiology. However, PF should always be considered when the clinical presentation is suggestive, regardless of the etiology. Penile manipulation and roll over in bed were the most common non-sexual causes. These cases are related to low-energy traumas, usually leading to unilateral rupture of corpus cavernosum. Urethral involvement is uncommon but may be present. Early treatment has good long-term clinical outcome, especially when performed in specialized centers with extensive experience in FP.

Lessons learned after 20 years' experience with penile fracture

ABSTRACT Objective: To report our experience over the past 20 years in the diagnosis and surgical treatment of penile fracture (PF). Materials and methods: Between January 1997 and January 2017, patients with clinical diagnosis of PF were admitted to our facility and retrospectively assessed. Medical records were reviewed for clinical presentation, etiology and operative findings. Postoperative complications, sexual and urinary function were evaluated. Results: Sexual trauma was the main etiological factor, responsible for 255 cases (88.5%): 110 (43.1%) occurred with the "doggy style" position, 103 (40.3%) with "man on top" position, 31 (12.1%) with the "woman on top" position and 11 (4.3%) in other sexual positions. The most common findings in the clinical presentation were hematoma, in all cases and detumescence in 238 (82.6%). Unilateral corpus cavernosum injuries were found in 199 (69%) patients and bilateral in 89 (31%) patients. Urethral injuries were observed in 54 (18.7%) cases. Nine (14.7%) patients developed erectile dysfunction and eight (13.1%) had penile curvature. Only two (3.7%) patients had complications after urethral reconstruction. Conclusions: PF has typical clinical presentation and no need for additional tests in most cases. Hematoma and immediate penile detumescence are the most common clinical findings. Sexual activity was the most common cause. The 'doggy style' and 'man-on-top' was the most common positions and generally associated with more severe lesions. Concomitant urethral injury should be considered in cases of highenergy trauma. Surgical reconstruction produces satisfactory results, however, it can lead to complications, such as erectile dysfunction and penile curvature.

Linear growth and bone metabolism in pediatric patients with inflammatory bowel disease / Crescimento linear e metabolismo ósseo em pacientes pediátricos com doença inflamatória intestinal

Abstract Objective: To review the pathophysiology and evaluation methods of linear growth and bone mineral density in children and adolescents diagnosed with inflammatory bowel disease. Source of data: Narrative review carried out in the PubMed and Scopus databases through an active search of the terms: inflammatory bowel disease, growth, failure to thrive, bone health, bone mineral density, and children and adolescents, related to the last ten years, searching in the title, abstract, or keyword fields. Synthesis of findings: Inflammatory bowel diseases of childhood onset may present as part of the clinical picture of delayed linear growth in addition to low bone mineral density. The presence of a chronic inflammatory process with elevated serum levels of inflammatory cytokines negatively interferes with the growth rate and bone metabolism regulation, in addition to increasing energy expenditure, compromising nutrient absorption, and favoring intestinal protein losses. Another important factor is the chronic use of glucocorticoids, which decreases the secretion of growth hormone and the gonadotrophin pulses, causing pubertal and growth spurt delay. In addition to these effects, they inhibit the replication of osteoblastic lineage cells and stimulate osteoclastogenesis. Conclusion: Insufficient growth and low bone mineral density in pediatric patients with inflammatory bowel disease are complex problems that result from multiple factors including chronic inflammation, malnutrition, decreased physical activity, late puberty, genetic susceptibility, and immunosuppressive therapies, such as glucocorticoids.

Resumo Objetivo: Revisar a fisiopatologia e os métodos de avaliação do crescimento linear e densidade mineral óssea em crianças e adolescentes com diagnóstico de doença inflamatória intestinal. Fontes dos dados: Revisão narrativa a partir de pesquisa nas bases de dados PubMed e Scopus por meio de busca ativa dos termos inflammatory bowel disease, growth, failure to thrive, bone health, bone mineral density, children e adolescents nos últimos dez anos e com busca nos campos título, resumo ou palavra-chave. Resumo dos achados: As doenças inflamatórias intestinais com início na infância podem apresentar como parte do quadro clínico atraso do crescimento linear, além de baixa densidade mineral óssea. A presença de processo inflamatório crônico com elevados níveis séricos das citocinas inflamatórias interfere negativamente na velocidade do crescimento e na regulação do metabolismo ósseo, além de aumentar o gasto energético, comprometer a absorção de nutrientes e favorecer perdas proteicas intestinais. Outro fator importante é o uso crônico de glicocorticoides, que diminuem a secreção de hormônio do crescimento e dos pulsos das gonadotrofinas e ocasionam atraso puberal e no estirão do crescimento. Além desses efeitos, inibem a reprodução das células da linhagem osteoblástica e estimulam a osteoclastogênese. Conclusão: A insuficiência do crescimento e a baixa densidade mineral óssea em pacientes pediátricos com doença inflamatória intestinal são problemas complexos e que decorrem de múltiplos fatores, inclusive inflamação crônica, desnutrição, diminuição da atividade física, puberdade tardia, suscetibilidade genética a terapias imunossupressoras, como os glicocorticoides.

Soil patterns and foliar standards for two cocoa clones in the States of Espírito Santo and Bahia, Brazil / Padrões de solo e normas foliares para dois clones de cacau cultivados nos Estados do Espírito Santo e Bahia, Brasil

ABSTRACT: The objective of this research was to establish soil patterns and foliar standards for clonal crops of cocoa CCN51 and PS1319 in the Atlantic regions within the northern Espírito Santo and southern Bahia States. Samples were collected from September to October 2015, in 45 high productive plots, being 23 plots of clone CCN51 and 22 of clone PS1319. Sufficiency ranges for soil and foliar standards were recommended for cocoa clones CCN51 and PS1319 planted in the Northern Espírito Santo and Southern Bahia states. Differences in the contents of foliar macronutrients K, Ca, Mg, S and micronutrients Fe and Mn, were verified between clones CCN51 and PS1319. Differences reported for standards from different geographical regions confirmed that these standards need to be regional and specific for different cocoa clones.

RESUMO: O objetivo deste trabalho foi estabelecer padrões de solo e padrões foliares para culturas clonais de cacau CCN51 e PS1319 nas regiões do Atlântico no norte do Espírito Santo e no sul da Bahia. As amostras foram coletadas de setembro a outubro de 2015, em 45 parcelas de alta produtividade, sendo 23 parcelas do clone CCN51 e 22 do clone PS1319. As faixas de suficiência para solo e padrões foliares foram sugeridas para os clones de cacau CCN51 e PS1319 plantados no norte do Espírito Santo e no sul da Bahia. Diferenças nos teores dos macronutrientes foliares K, Ca, Mg, S e micronutrientes Fe e Mn foram verificadas entre os clones CCN51 e PS1319. As diferenças relatadas para padrões de diferentes regiões geográficas permitem confirmar que esses padrões precisam ser regionais e específicos para diferentes clones de cacau.

Predicting response to treatment and discriminating bipolar and depression symptoms using Hamilton Depression Rating Scale / Preditor de resposta ao tratamento e discriminação de pacientes com depressão maior e transtorno bipolar pela Escala Hamilton de Depressão

ABSTRACT Objective The present study aims to compare the diagnostic ability of the HAMD 17 items with shorter versions of 7 and 6 items. Methods A total of 133 patients from a 6 month clinical trial diagnosed with mood disorders (60.2% with Major Depressive Disorder and 39.8% with bipolar type I disorder) were recruited. Results The 17 items HAMD scale showed similar results as compared with shorter versions. Furthermore, almost all patients' diagnosed with Major Depressive Disorder scored more compared to Bipolar Disorder, but the difference was not significant. Conclusion This study allows that the use of a shorter version of HAMD might be an adequate possibility, and also that depressive symptoms were similar among groups.

RESUMO Objetivo O presente estudo tem por objetivo investigar a habilidade diagnóstica da HAMD 17 comparada a versões breves de 7 e 6 itens. Métodos Foram selecionados 133 participantes recrutados de um ensaio clínico (60,2% com Depressão Maior e 39,8% com Transtorno Bipolar tipo I). Resultados A versão de 17 itens da HAMD mostrou resultados similares quando comparada às versões breves. Ademais, quase todos os pacientes diagnosticados com Depressão Maior apresentaram maiores pontuações, contudo, essa diferença não foi estatisticamente significativa. Conclusão Este estudo demonstra que o uso de uma versão breve da HAMD pode ser uma possibilidade adequada e que os sintomas depressivos se mostraram similares entre os grupos de bipolares e depressivos.

Psychotria viridis: Chemical constituents from leaves and biological properties

ABSTRACT The phytochemical study of hexane, chloroform and methanol extracts from leaves of Psychotria viridis resulted in the identification of: the pentacyclic triterpenes, ursolic and oleanolic acid; the steroids, 24-methylene-cycloartanol, stigmasterol and β-sitosterol; the glycosylated steroids 3-O-β-D-glucosyl-β-sitosterol and 3-O-β-D-glucosyl-stigmasterol; a polyunsaturated triterpene, squalene; the esters of glycerol, 1-palmitoylglycerol and triacylglycerol; a mixture of long chain hydrocarbons; the aldehyde nonacosanal; the long chain fat acids hentriacontanoic, hexadecanoic and heptadenoic acid; the ester methyl heptadecanoate; the 4-methyl-epi-quinate and two indole alkaloids, N,N-dimethyltryptamine (DMT) and N-methyltryptamine. The chemical structures were determined by means of spectroscopic (IR, 1H and 13C NMR, HSQC, HMBC and NOESY) and spectrometric (CG-MS and LCMS-ESI-ITTOF) methods. The study of biologic properties of P. viridis consisted in the evaluation of the acetylcholinesterase inhibition and cytotoxic activities. The hexane, chloroform, ethyl acetate and methanol extracts, the substances 24-methylene-cycloartanol, DMT and a mixture of 3-O-β-D-glucosyl-β-sitosterol and 3-O-β-D-glucosyl-stigmasterol showed cholinesterase inhibiting activity. This activity induced by chloroform and ethyl acetate extracts was higher than 90%. The methanol and ethyl acetate extracts inhibit the growth and/or induce the death of the tumor cells strains B16F10 and 4T1, without damaging the integrity of the normal cells BHK and CHO. DMT also demonstrated a marked activity against tumor cell strains B16F10 and 4T1.

Brazilian multicenter study of 71 patients with juvenile-onset Takayasu's arteritis: clinical and angiographic features / Estudo multicêntrico brasileiro de 71 pacientes com arterite de Takayasu juvenil: características clínicas e angiográficas

ABSTRACT Objective: To describe the clinical and angiographic characteristics of Takayasu's arteritis in Brazilian children and adolescents. Methods: A retrospective data collection was performed in 71 children and adolescents followed in 10 Brazilian reference centers in Pediatric Rheumatology. The evaluation was carried out in three different time points: from onset of symptoms to diagnosis, from the 6 th to 12th month of diagnosis, and in the last visit. Results: Of 71 selected patients, 51 (71.8%) were girls. The mean age of onset of symptoms and of time to diagnosis was 9.2 (± 4.2) years and 1.2 (± 1.4) years, respectively. At the end of the study, 20 patients were in a state of disease activity, 39 in remission and 5 had evolved to death. The most common symptoms in baseline assessment, second evaluation, and final evaluation were, respectively: constitutional, musculoskeletal, and neurological symptoms. A decrease in peripheral pulses was the most frequent cardiovascular signal, and an increase in erythrocyte sedimentation rate was the most frequent laboratory finding in all three evaluation periods. The tuberculin test was positive in 41% of those tested. Stenosis was the most frequent angiographic lesion, abdominal artery was the most affected segment, and angiographic type IV the most frequent. Most (90%) participants were treated with glucocorticoids, 85.9% required another immunosuppressive drug, and 29.6% underwent angioplasty. Conclusion: This is the largest study on juvenile-onset Takayasu arteritis, and a high number of patients under the age of 10 years, with predominance of constitutional symptoms early in the disease, was observed.

RESUMO Objetivo: Descrever as características clínicas e angiográficas da arterite de Takayasu em crianças e adolescentes brasileiros. Métodos: Foi feita coleta retrospectiva de dados de 71 crianças e adolescentes acompanhados em 10 centros brasileiros de referência em reumatologia pediátrica. A avaliação foi feita em três tempos: início dos sintomas até o diagnóstico, do 6º ao 12º mês de diagnóstico e última consulta. Resultados: Dos 71 pacientes selecionados, 51 (71,8%) eram meninas. As médias de idade de início dos sintomas e de tempo até diagnóstico foram 9,2 anos (± 4,2) e 1,2 anos (± 1,4), respectivamente. No fim do estudo, 20 pacientes estavam em atividade de doença, 39 em remissão e cinco haviam evoluído a óbito. Os sintomas mais frequentes nas avaliação inicial, segunda avaliação e avaliação final foram, respectivamente, os constitucionais, os musculoesqueléticos e os neurológicos. A redução de pulsos periféricos foi o sinal cardiovascular mais frequente e a elevação da velocidade de hemossedimentação foi o achado laboratorial mais frequente nos três períodos de avaliação. O teste tuberculínico foi reagente em 41%. A estenose foi a lesão angiográfica mais encontrada, a artéria abdominal foi o segmento mais afetado e tipo angiográfico IV o mais frequente. A maioria (90%) fez terapia com glicocorticoides, 85,9% necessitaram de outro imunossupressor e 29,6% foram submetidos à angioplastia. Conclusão: Este é o maior estudo de arterite de Takayasu juvenil e nós observar elevado número de pacientes com idade inferior a 10 anos e a predominância de sintomas constitucionais no início da doença.

Diretrizes de conduta e tratamento de síndromes febris periódicas associadas a febre familiar do Mediterrâneo / Guidelines for the management and treatment of periodic fever syndromes familial Mediterranean fever

Resumo Objetivo: Estabelecer diretrizes baseadas em evidências científicas para manejo da febre familiar do Mediterrâneo (FFM). Descrição do método de coleta de evidência: A diretriz foi elaborada a partir de 5 questões clínicas que foram estruturadas por meio do PICO (Paciente, Intervenção ou Indicador, Comparação e Outcome), com busca nas principais bases primárias de informação científica. Após definir os estudos potenciais para sustento das recomendações, esses foram graduados pela força da evidência e pelo grau de recomendação. Resultados: Foram recuperados, e avaliados pelo título e resumo, 10.341 trabalhos e selecionados 46 artigos para sustentar as recomendações. Recomendações: 1. O diagnóstico da FFM é baseado nas manifestações clínicas, caracterizadas por episódios febris recorrentes associados a dor abdominal, torácica ou artrite de grandes articulações; 2. A FFM é uma doença genética que apresenta traço autossômico recessivo ocasionada por mutação no gene MEFV; 3. Exames laboratoriais são inespecíficos e demonstram níveis séricos elevados de proteínas inflamatórias na fase aguda da doença, mas também, com frequência, níveis elevados mesmo entre os ataques. Níveis séricos de SAA podem ser especialmente úteis no monitoramento da eficácia do tratamento; 4. A colchicina é a terapia de escolha e demonstrou eficácia na prevenção dos episódios inflamatórios agudos e progressão para amiloidose em adultos; 5. Com base na informação disponível, o uso de medicamentos biológicos parece ser opção para pacientes com FFM que não respondem ou que são intolerantes à terapia com colchicina.

Abstract Objective: To establish guidelines based on scientific evidence for the management of familial Mediterranean fever. Description of the evidence collection method: The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. Results: 10,341 articles were retrieved and evaluated by title and abstract; from these, 46 articles were selected to support the recommendations. Recommendations: 1. The diagnosis of FMF is based on clinical manifestations, characterized by recurrent febrile episodes associated with abdominal pain, chest or arthritis of large joints; 2. FMF is a genetic disease presenting an autosomal recessive trait, caused by mutation in the MEFV gene; 3. Laboratory tests are not specific, demonstrating high serum levels of inflammatory proteins in the acute phase of the disease, but also often showing high levels even between attacks. SAA serum levels may be especially useful in monitoring the effectiveness of treatment; 4. The therapy of choice is colchicine; this drug has proven effectiveness in preventing acute inflammatory episodes and progression towards amyloidosis in adults; 5. Based on the available information, the use of biological drugs appears to be an alternative for patients with FMF who do not respond or are intolerant to therapy with colchicine.

Diretrizes de conduta e tratamento de síndromes febris periódicas associadas à criopirina (criopirinopatias – CAPS) / Guidelines for the management and treatment of periodic fever syndromes

Resumo Objetivo: Estabelecer diretrizes baseadas em evidências científicas para manejo das síndromes periódicas associadas à criopirina (criopirinopatias – Caps). Descrição do método de coleta de evidência: A diretriz foi elaborada a partir de quatro questões clínicas que foram estruturadas por meio do PICO (Paciente, Intervenção ou Indicador, Comparação e Outcome), com busca nas principais bases primárias de informação científica. Após definir os estudos potenciais para sustento das recomendações, esses foram graduados pela força da evidência e pelo grau de recomendação. Resultado: Foram recuperados, e avaliados pelo título e resumo, 1.215 artigos e selecionados 42 trabalhos para sustentar as recomendações. Recomendações: 1. O diagnóstico de Caps é baseado na anamnese e nas manifestações clínicas e posteriormente confirmado por estudo genético. Pode se manifestar sob três fenótipos: FCAS (forma leve), MWS (forma intermediária) e Cinca (forma grave). Avaliações neurológica, oftalmológica, otorrinolaringológica e radiológica podem ser de grande valia na distinção entre as síndromes; 2. O diagnóstico genético com análise do gene NLRP3 deve ser conduzido nos casos suspeitos de Caps, isto é, indivíduos que apresentam, antes dos 20 anos, episódios recorrentes de inflamação expressa por urticária e febre moderada; 3. As alterações laboratoriais incluem leucocitose e elevação nos níveis séricos de proteínas inflamatórias; 4. Terapias alvo dirigidas contra a interleucina 1 levam a rápida remissão dos sintomas na maioria dos pacientes. Contudo, existem limitações importantes em relação à segurança em longo prazo. Nenhuma das três medicações anti-IL1β evita progressão das lesões ósseas.

Abstract Objective: To establish guidelines based on cientific evidences for the management of cryopyrin associated periodic syndromes. Description of the evidence collection method: The Guideline was prepared from 4 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. Results: 1215 articles were retrieved and evaluated by title and abstract; from these, 42 articles were selected to support the recommendations. Recommendations: 1. The diagnosis of CAPS is based on clinical history and clinical manifestations, and later confirmed by genetic study. CAPS may manifest itself in three phenotypes: FCAS (mild form), MWS (intermediate form) and CINCA (severe form). Neurological, ophthalmic, otorhinolaryngological and radiological assessments may be highly valuable in distinguishing between syndromes; 2. The genetic diagnosis with NLRP3 gene analysis must be conducted in suspected cases of CAPS, i.e., individuals presenting before 20 years of age, recurrent episodes of inflammation expressed by a mild fever and urticaria; 3. Laboratory abnormalities include leukocytosis and elevated serum levels of inflammatory proteins; and 4. Targeted therapies directed against interleukin-1 lead to rapid remission of symptoms in most patients. However, there are important limitations on the long-term safety. None of the three anti-IL-1β inhibitors prevents progression of bone lesions.

Diretrizes de conduta e tratamento de síndromes febris periódicas: síndrome de febre periódica, estomatite aftosa, faringite e adenite / Guidelines for the management and treatment of periodic fever syndromes: periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome

Resumo Objetivo: Estabelecer diretrizes baseadas em evidências científicas para manejo da síndrome de febre periódica, estomatite aftosa, faringite e adenite (PFAPA). Descrição do método de coleta de evidência: A Diretriz foi elaborada a partir de cinco questões clínicas que foram estruturadas por meio do Pico (Paciente, Intervenção ou Indicador, Comparação e Outcome), com busca nas principais bases primárias de informação científica. Após definir os estudos potenciais para sustento das recomendações, esses foram graduados pela força da evidência e pelo grau de recomendação. Resultados: Foram recuperados e avaliados pelo título e resumo 806 trabalhos e selecionados 32 artigos, para sustentar as recomendações. Recomendações: 1. O diagnóstico da PFAPA é clínico e de exclusão, deve a suspeita ser considerada em crianças que apresentam episódios febris de origem indeterminada recorrentes e periódicos ou amidalites de repetição, intercalados com períodos assintomáticos, sobretudo em crianças em bom estado geral e com desenvolvimento pondero-estatural mantido; 2. Os achados laboratoriais são inespecíficos. Não existem alterações patognomônicas nos exames complementares; 3. A evidência que sustenta a indicação do tratamento cirúrgico (tonsilectomia com ou sem adenoidectomia) é baseada em dois ensaios clínicos randomizados não cegos que incluíram pequeno número de pacientes; 4. O uso de prednisona no início do quadro febril em pacientes com PFAPA mostrou ser eficaz. Melhores evidências ainda são necessárias para apoiar seu uso na PFAPA; 5. Apesar de os resultados obtidos de estudos com inibidores de IL-1ß serem promissores, esses são limitados a poucos relatos de casos.

Abstract Objective: To establish guidelines based on scientific evidence for the management of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. Description of the evidence collection method: The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. Results: 806 articles were retrieved and evaluated by title and abstract; from these, 32 articles were selected to support the recommendations. Recommendations: 1. PFAPA is a diagnosis of exclusion established on clinical grounds, and one must suspect of this problem in children with recurrent and periodic febrile episodes of unknown origin, or with recurrent tonsillitis interspersed with asymptomatic periods, especially in children in good general condition and with preservation of weight and height development. 2. Laboratory findings are nonspecific. Additional tests do not reveal pathognomonic changes. 3. The evidence supporting an indication for surgical treatment (tonsillectomy with or without adenoidectomy), is based on two non-blinded randomized clinical trials with small numbers of patients. 4. The use of prednisone at the onset of fever in patients with PFAPA proved to be an effective strategy. There is still need for more qualified evidence to support its use in patients with PFAPA. 5. Despite promising results obtained in studies with IL-1β inhibitors, such studies are limited to a few case reports.

EEG in epilepsy: sensibility and specificity / EEG em epilepsia: sensibilidade e especificidade

Objective: the aim of this study was to determine the sensitivity (presence of epileptiform discharges in the EEGs of patientswith epilepsy) and specificity (absence of discharges in the EEGs in people without epilepsy) of EEG. Methodology: all EEGs performed at the Clinic Santa Vitória, in Campina Grande, PB, from April 2001 to April 2010 were reviewed. All recordings were performed in accordance with international standards for fixing the electrodes, minimum time of registration and methods activation (intermittent photic stimulation and hyperventilation). The reports were divided into 1) patients with epilepsy, previously diagnosed by neurologists, and 2) patients without epilepsy. For both groups, we evaluated the sensitivity and specificity of the EEG. We used SPSS for statistical tests. The study was approved by the Ethics Committee of UEPB. 10,408 EEGs were reviewed. Results: epileptiform discharges occurred in 1412 (13.56%). Among those with epilepsy, discharges occurred in 643 (45.57%) - true-positive. Among those who did not have epilepsy, in 54.43% - false positives. From a total of 8,996 (86.44%) EEGs without discharges, 1,276 (14.14%) were from the group of patients with epilepsy - false-negative and 7,720 (85.78%) were from the group of patients without epilepsy - true negative. The positive likelihood ratio test showed that the probability of finding EEG discharges is four times higher among patients with epilepsy compared to those who do not have epilepsy. The negative likelihood ratio test showed no differences between false negative and true negative. In general, a sensitivity of 33.5% and a specificity of 90.9%, with no differences in age and gender was observed. Therefore, EEG showed high specificity but low sensitivity as a diagnostic method in epilepsy...

Objetivo: o objetivo deste estudo foi verificar a sensibilidade (presença de descargas em EEGs de portadores de epilepsia) e a especificidade (ausência de descargas em EEGs de sem epilepsia) do EEG. Metodologia: foram revisados todos os EEGs realizados na Clínica Santa Vitória, em Campina Grande, PB, no período de abril de 2001 a abril de 2010. Todos os registros foram realizados de acordo com padrões internacionais para a fixação dos eletrodos, tempo mínimo de registro e métodos de ativação (fotoestimulação intermitente e hiperventilação). Os laudos foram divididos em 1) pacientes portadores de epilepsia, previamente diagnosticada por neurologistas, e 2) pacientes sem epilepsia. Para ambos os grupos, estudou-se a sensibilidade e a especificidade do EEG. Foram utilizados testes estatísticos através do programa SPSS. O estudo foi aprovado pelo Comitê de Ética da UEPB. Foram revisados 10.408 EEGs. Resultados: descargas epileptiformes ocorreram em 1412 (13,56%). Dentre os portadores de epilepsia, descargas ocorreram em 643 (45,57%) - verdadeiros-positivos. Dentre os que não apresentam epilepsia, em 54,43% - falsos-positivos. De um total de 8.996 (86,44%) de EEGs sem descargas, 1.276 (14,14%) eram do grupo de portadores de epilepsia - falsos-negativos e 7.720 (85,78%) eram do grupo de pacientes sem epilepsia - verdadeiros-negativos. O teste de verossimilhança positiva revelou que a probabilidade de ocorrerem descargas é quarto vezes maior dentre os portadores de epilepsia, comparados aos que não apresentam epilepsia. Já o teste de verossimilhança negativa não evidenciou diferenças significativas entre falsos-negativos e verdadeiros-negativos. De modo geral, foi observada uma sensibilidade de 33,5% e uma especificidade de 90,9%, sem diferenças quanto à idade e ao gênero. O EEG apresentou, portanto, alta especificidade, mas uma baixa sensibilidade, como método diagnóstico auxiliar nas epilepsias...