The Second Highest Prevalence of Celiac Disease Worldwide: Genetic and Metabolic Insights in Southern Brazilian Mennonites.

Celiac disease (CD), despite its high morbidity, is an often-underdiagnosed autoimmune enteropathy. Using a modified version of the Brazilian questionnaire of the 2013 National Health Survey, we interviewed 604 Mennonites of Frisian/Flemish origin that have been isolated for 25 generations. A subgroup of 576 participants were screened for IgA autoantibodies in serum, and 391 participants were screened for HLA-DQ2.5/DQ8 subtypes. CD seroprevalence was 1:29 (3.48%, 95% CI = 2.16-5.27%) and biopsy-confirmed CD was 1:75 (1.32%, 95% CI = 0.57-2.59%), which is superior to the highest reported global prevalence (1:100). Half (10/21) of the patients did not suspect the disease. HLA-DQ2.5/DQ8 increased CD susceptibility (OR = 12.13 [95% CI = 1.56-94.20], p = 0.003). The HLA-DQ2.5 carrier frequency was higher in Mennonites than in Brazilians (p = 7 × 10-6). HLA-DQ8 but not HLA-DQ2.5 carrier frequency differed among settlements (p = 0.007) and was higher than in Belgians, a Mennonite ancestral population (p = 1.8 × 10-6), and higher than in Euro-Brazilians (p = 6.5 × 10-6). The glutathione pathway, which prevents reactive oxygen species-causing bowel damage, was altered within the metabolic profiles of untreated CD patients. Those with lower serological positivity clustered with controls presenting close relatives with CD or rheumatoid arthritis. In conclusion, Mennonites have a high CD prevalence with a strong genetic component and altered glutathione metabolism that calls for urgent action to alleviate the burden of comorbidities due to late diagnosis.

Adalimumab Serum Concentrations, Clinical and Endoscopic Disease Activity in Crohn's Disease: A Cross-Sectional Multicentric Latin American Study.

Despite some variability in ideal serum Adalimumab (ADA) concentrations, there is increasing evidence that higher concentrations of anti-TNF-α agents can be associated with sustained efficacy, and low or undetectable levels may lead to loss of response. This study aims to correlate serum ADA concentrations with clinical and endoscopic activity in patients with Crohn's disease (CD). A cross-sectional and multicentric study was performed with patients with CD, who used ADA for at least 24 weeks. Patients were allocated into groups according to the presence of clinical or endoscopic disease activity. Serum ADA concentrations were measured and compared between groups. Overall, 89 patients were included. A total of 27 patients had clinically active CD and 62 were in clinical remission. Forty patients had endoscopic disease activity and 49 were in endoscopic remission. The mean serum ADA concentration was 10.2 µg/mL in patients with clinically active CD and 14.3 µg/mL in patients in clinical remission (p = 0.395). The mean serum ADA concentration in patients with endoscopic activity was 11.3 µg/mL as compared to 14.5 µg/mL in those with endoscopic remission (p = 0.566). There was no difference between serum ADA concentrations regarding clinical or endoscopic activity in CD, as compared to patients in remission.

Periodontitis in rheumatoid arthritis: a case-control study in a brazilian sample

To investigate the presence of periodontitis in RA patients comparing it with controls in a Brazilian sample. Methods: This is a case control study conducted in a public health rheumatologic center. One hundred and sixteen RA patients and 68 paired controls were compared for epidemiological data and presence of periodontal disease evaluated by number of remaining teeth, presence of bacterial plaque, bleeding on probing, probing depth and clinical level of gingival insertion. In addition, data on comorbidities was collected. Results: RA patients and controls have the same amount of teeth loss (P = 0.84). RA patients had more calculus (P = 0.02); dental plaques (P = 0.04); gingival recession (P = 0.02) and bleeding (P = 0.01). Although the number of individuals with periodontitis was higher in RA patients, the severity of periodontitis was similar in both groups (P = ns). Presence of diabetes and hypothyroidism also associated with periodontitis (P = 0.01 and 0.02 respectively). In a model of logistic regression built to assess the independence of association of RA and its comorbidities with periodontitis, only diabetes and RA remained independent. Conclusion: This case control study shows higher frequency of periodontitis in RA patients than controls

Effects of aging and the body mass index on male sex hormones: a cross-sectional study in 701 Brazilian men / Efeitos do envelhecimento e do índice de massa corporal sobre os hormônios sexuais masculinos: um estudo transversal em 701 homens brasileiros

Background: Some studies indicated that body mass index (BMI) is inversely proportional to serum testosterone concentrations in men. Purposes: This study aimed to analyze the effects of aging and obesity on total testosterone (TT), free testosterone (FT), bioavailable testosterone (BT), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) levels. Methods: A cross-sectional study was performed to assess the clinical and laboratory profiles of 701 patients treated at a private urology clinic in Ponta Grossa, Brazil, from January 2016 to December 2018. Results: Patients' age ranged from 16 to 88 years (mean, 56.9 ± 13.62 years). Age did not significantly influence serum TT concentrations, except compared to patients aged >70 years. However, changes were observed in FT and BT (p < 0.05). The mean SHBG increased with age (p < 0.05). A tendency toward LH elevation was observed in older patients, but it was not statistically significant. An inverse proportional relationship between TT, FT, and BT and the testosterone deficiency rate (TT < 300 ng/dL) was observed within BMI groups (p < 0.05). The testosterone deficiency rate was 21.5% in individuals with normal BMI, 29% in overweight individuals, and 37% in obese individuals. Conclusions: Aging affected the testosterone concentrations in men and became increasingly evident using FT and BT instead of TT. SHBG increased with age. Obesity was associated with a decrease in TT, FT, and BT but also increased the rate of hypogonadism. (AU)

Fundamentos: Alguns estudos indicam que o índice de massa corporal (IMC) é inversamente proporcional à con-centração de testosterona sérica em homens. Objetivos: O objetivo deste estudo é analisar o efeito do envelhe-cimento e da obesidade na testosterona biodisponível total e livre, bem como nos níveis de hormônio luteinizante e globulina ligadora de hormônio sexual. Métodos: Foi realizado um estudo transversal abordando o perfil clínico e laboratorial de 701 pacientes atendidos em uma clínica privada de urologia em Ponta Grossa, Brasil, de janei-ro de 2016 a dezembro de 2018. Resultados: A idade dos pacientes variou de 16 a 88 anos (média de 56,9 ± 13,62 anos). A idade não influenciou significativamente as concentrações séricas de testosterona total, exceto quando comparada a pacientes com mais de 70 anos. No entanto, foi observada diferença na testosterona livre e biodisponível (p <0,05). A média de globulina de ligação aos hormônios sexuais aumentou com a idade (p <0,05). Embora uma tendência à elevação da luteinização tenha sido observada em pacientes mais idosos, ela não foi significativa. Relação inversa entre testosterona total, livre e biodisponível e taxa de deficiência de testosterona (testosterona total <300 ng / dL) foi observada dentro dos grupos de índice de massa corporal (p <0,05). A taxa de deficiência de testosterona em indivíduos com índice de massa corporal normal foi de 21,5%, indivíduos com sobre-peso foi de 29% e em indivíduos com obesidade foi de 37%. Conclusões: O envelhecimento afetou a concentração de testosterona em homens, mais evidente ao avaliar testosterona livre e biodisponível em vez de testosterona total. A globulina de ligação aos hormônios sexuais aumentou com a idade. A obesidade foi associada à redução da testosterona total, livre e biodisponível e ao aumento da taxa de hipogonadismo. (AU)

Índice de independência funcional de pacientes pós-acidente vascular cerebral submetidos a um programa de reabilitação multiprofissional / Functional independence index of patients submitted to multiprofessional rehabilitation program after cerebrovascular accident

Acidente Vascular Cerebral (AVC) pode causar óbito ou sequelas motoras e funcionais de intensidade variável. O objetivo do estudo foi avaliar o índice de independência funcional de pacientes pós-Acidente Vascular Cerebral submetidos a um programa de reabilitação multiprofissional. Trata-se de estudo retrospectivo por meio de revisão dos prontuários de sobreviventes de lesão vascular na artéria cerebral média, admitidos entre 2014 e 2019 em hospital público de Curitiba - Paraná, e que foram analisados na admissão e na alta por meio da Escala de Rankin modificada (mRS). Foram aplicados teste Qui-Quadrado, Mann-Whitney e Wilcoxon, considerando p < 0,05 %. A amostra, composta por 64 pacientes, teve predomínio masculino (56 %), faixa etária média de 59 anos, eapresentou como sequelas principais déficit motor (98 %), disartria (51 %), afasia (46 %), dor (45 %) e incontinência urinária (42 %). Houve diferença significativa entre os escores aferidos por meio da mRS na admissão e na alta, com maior independência funcional após realização do programa de reabilitação proposto (p < 0,001). Conclui-se que a participação no programa refletiu em ganho de autonomia no autocuidado e na realização de atividades diárias pelos pacientes. [au]

A cerebrovascular accident (CVA) can cause death or motor and functional consequences of variable intensity. This study analyzed the rate of functional independence of patients after a cerebrovascular accident and a multi professional rehabilitation program. This was a retrospective research analyzing the medical charts of middle cerebral artery stroke survivors, admitted to a public hospital at Curitiba-Paraná between 2014 and 2019. The participants were analyzed at admission and discharge using the Modified Rankin Scale (mRS). The Chi-Squared test, Mann-Whitney test and Wilcoxon tests were applied, considering p<0.05%. The sample was composed of 64 patients, mainly men (56%), with a mean age of 59 years old. The main stroke sequelae were motor deficit (98%), dysarthria (51%), aphasia (46%), pain (45%) and urinary incontinence (42%). There was a significant difference between the mRS scores at admission and discharge, with greater functional independence after the proposed rehabilitation program (p <0.001). It is concluded that participation in the program led to increased autonomy in self-care and daily activities for the patients.[au]

The impact of social isolation by COVID-19 on the epidemiological and clinical profiles of the burn patients. A retrospective study.

BACKGROUND: Social isolation, imposed by the COVID-19 pandemic, may imply changes in the clinical-demographic and epidemiological profiles of burn trauma victims. OBJECTIVE: Evaluate the changes in the epidemiological profile of patients with burns that resulted in hospitalization during the social isolation period due to the COVID-19 pandemic, comparing with the same period in the previous year. METHODS: The medical records of burn patients who were hospitalized in our Burn Center during the local confinement period (March 18th to August 31st, 2020) and during the same period in 2019 were analyzed. Data on demographic, clinical and hospitalization aspects were studied. RESULTS: 470 patients were evaluated. In the pediatric population, a significant increase in the number of cases up to 2 years old (P = 0.0003), median of %TBSA (P = 0.037), full-thickness burns (P < 0.0001), involvement of hands (P = 0.024), debridement (P = 0.046) and grafting (P = 0.032) procedures, and higher scores of severity (P < 0.0001) were noted. In the adult population, it was only observed an increase in the burn-hospitalization interval (P = 0.029). CONCLUSION: The pediatric population was heavily impacted by the imposed period of social isolation, presenting a greater severity of burns. In contrast, the epidemiology of burns for the adult population was slightly altered during the pandemic period.

Quality of life of patients with Parkinson's disease: a comparison between preoperative and postoperative states among those who were treated with deep brain stimulation / Qualidade de vida de pacientes com doença de Parkinson: uma comparação dos estados pré-operatório e pós-operatório daqueles tratados com estimulação cerebral profunda

ABSTRACT Background: Deep brain stimulation (DBS) is a well-established procedure for treating Parkinson's disease (PD). Although its mechanisms of action are still unclear, improvements in motor symptoms and reductions in medication side effects can be achieved for a significant proportion of patients, with consequent enhancement of quality of life. Objective: To investigate the impact of DBS on the quality of life of PD patients. Methods: This was a retrospective longitudinal study with collection of historical data in a neurosurgery center, from June 2019 to December 2020. The sample was obtained according to convenience, and the Parkinson's Disease Questionnaire (PDQ-39), Unified Parkinson's Disease Rating Scale (UPDRS) III and IV, Trail-Making Test and Verbal Fluency Test were used. Results: Data were collected from 17 patients (13 with subthalamic nucleus DBS and 4 with globus pallidus pars interna DBS). Significant improvement (p=0.008) on the UPDRS III was observed in comparing the preoperative without DBS with the postoperative with DBS. About 47.0% of the patients showed post-surgical improvement in QoL (p=0.29). Thirteen patients were able to complete part A of the Trail-Making Test and four of these also completed part B. Almost 60% of the patients scored sufficiently on the semantic test, whereas only 11.8% scored sufficiently on the orthographic evaluation. No association between implant site and test performance could be traced. Conclusions: Improvements in quality of life and motor function were observed in the majority of the patients enrolled. Despite the limitations of this study, DBS strongly benefits a significant proportion of PD patients when well indicated.

RESUMO Antecedentes: A estimulação cerebral profunda (ECP) é um procedimento bem estabelecido para o tratamento da doença de Parkinson (DP). Embora seus mecanismos de ação não sejam claros, a melhora dos sintomas motores e a redução dos efeitos colaterais dos medicamentos são contempladas em uma proporção significativa de pacientes, com melhora da qualidade de vida. Objetivo: Investigar o impacto da ECP na qualidade de vida de pacientes em DP. Métodos: Trata-se de um estudo longitudinal retrospectivo, com coleta de dados históricos em um centro de neurocirurgia, de junho de 2019 a dezembro de 2020. A amostra foi feita por conveniência, e os questionários Parkinson's Disease Questionnare (PDQ-39), Unified Parkinson's Disease Rating Scale (UPDRS) III e IV, Trail Making Test e Teste de Fluência Verbal foram utilizados. Resultados: Dos dados coletados de 17 pacientes (13 ECP em núcleo subtalâmico e ECP em globo pálido interno) notou-se melhora significativa (p=0,008) no UPDRS III ao se comparar o pré-operatório sem ECP com pós-operatório com ECP, e cerca de 47,0% deles apresentaram melhora pós-cirúrgica na qualidade de vida (p=0,29). Treze pacientes conseguiram completar a parte A do Trail Making Test e quatro também completaram a parte B. Quase 60,0% dos pacientes obtiveram pontuação suficiente no teste semântico, enquanto apenas 11,8% obtiveram pontuação suficiente na avaliação ortográfica. Não foi possível rastrear a associação entre local do implante e desempenho. Conclusões: Melhora na qualidade de vida e na função motora foi observada na maioria dos pacientes. Apesar das limitações do estudo, a ECP beneficia fortemente uma proporção significativa de pacientes em DP quando bem indicada.

Quality of life of patients with Parkinson's disease: a comparison between preoperative and postoperative states among those who were treated with deep brain stimulation.

BACKGROUND: Deep brain stimulation (DBS) is a well-established procedure for treating Parkinson's disease (PD). Although its mechanisms of action are still unclear, improvements in motor symptoms and reductions in medication side effects can be achieved for a significant proportion of patients, with consequent enhancement of quality of life. OBJECTIVE: To investigate the impact of DBS on the quality of life of PD patients. METHODS: This was a retrospective longitudinal study with collection of historical data in a neurosurgery center, from June 2019 to December 2020. The sample was obtained according to convenience, and the Parkinson's Disease Questionnaire (PDQ-39), Unified Parkinson's Disease Rating Scale (UPDRS) III and IV, Trail-Making Test and Verbal Fluency Test were used. RESULTS: Data were collected from 17 patients (13 with subthalamic nucleus DBS and 4 with globus pallidus pars interna DBS). Significant improvement (p=0.008) on the UPDRS III was observed in comparing the preoperative without DBS with the postoperative with DBS. About 47.0% of the patients showed post-surgical improvement in QoL (p=0.29). Thirteen patients were able to complete part A of the Trail-Making Test and four of these also completed part B. Almost 60% of the patients scored sufficiently on the semantic test, whereas only 11.8% scored sufficiently on the orthographic evaluation. No association between implant site and test performance could be traced. CONCLUSIONS: Improvements in quality of life and motor function were observed in the majority of the patients enrolled. Despite the limitations of this study, DBS strongly benefits a significant proportion of PD patients when well indicated.

Seropositivity for syphilis among Brazilian blood donors. A retrospective study 2015-2020.

INTRODUCTION: Syphilis is a transfusion-transmitted infection and the disease re-emerged in many countries, including Brazil, as a public health risk. OBJECTIVE: Evaluate the prevalence of positive serology in blood donations rejected by Hemobanco (Curitiba- PR) from January 2015 to December 2020, with special focus in syphilis. METHODOLOGY: In the studied period, we analyzed the number of blood donations discarded annually for each serological test performed on blood donors' samples, according to gender and donors age. RESULTS: Within the studied period, 134,741 blood donation were analyzed. 54.5 % of sample were male. Otherwise, it was observed a significant increase in the number of donations by females (P < 0.0001). There was an increase of 437 % in the prevalence of syphilis positive serology made by donors with ≥ 60 years. Besides that, it was noticed a significant increase in donations by aged people throughout these six years (P < 0.0001). The percentage of total blood donation deferred had a significant reduction, although it was observed an increase in the rate of discarded blood bags due to positive serology in the first 4 studied years. It was observed an increase of 20 % in positive syphilis serology. CONCLUSION: The greatest cause of discard of blood donations changed during the analyzed 5-years; there was an increase in seropositivity donations from donors with ≥ 60 years old. In 2015, Hepatitis B (0.8 %) was the most prevalent and in 2020, syphilis became more prevalent (0.82 %). The medical community should be aware of the rising number of cases of syphilis infection. There is an urgent need to implement actions against the dissemination of this disease.

Aplicação da imunoterapia no SUS: Impactos éticos e financeiros / Application of immunotherapy in the SUS: Ethical and financial impacts

Dados do Instituto Nacional do Câncer estimam que o Brasil terá 625 mil novos casos de câncer a cada ano do triênio 2020-2022. O Brasil, único país da América Latina com um sistema universal de saúde, apresentou grande avanço no tratamento do câncer. Nesse ínterim inclui-se a imunoterapia. Entretanto, o desafio ainda é longo e de custo muito elevado assim, o objetivo desta revisão foi discutir acerca da disponibilidade geral de imunoterapia no SUS. Assim, foi realizda pesquisa bibliográfica no Pubmed e Scielo com os descritores "Imunoterapia", "Sistema Único de Saúde" e "Oncologia". Selecionou-se 17 artigos. Em conclusão, a partir da incorporação da imunoterapia no SUS, estima-se aumento considerável na sobrevida. Todavia, a carência da disponibilidade orçamentária atrasa a implementação do tratamento. Ademais, são necessárias mais pesquisas e novas formas de seleção dos pacientes para a disponibilidade do tratamento a fim de não prejudicar o sistema público.

Data from the National Cancer Institute estimate that Brazil will have 625,000 new cases of cancer each year in the 2020-2022 triennium. Brazil, the only country in Latin America with a universal health system, has made great progress in cancer treatment. In the meantime, immunotherapy is included. However, the challenge is still long and costly, so the objective of this review was to discuss the general availability of immunotherapy in the SUS. Thus, a bibliographic research was carried out in Pubmed and Scielo with the descriptors "Immunotherapy", "Sistema Único de Saúde" and "Oncology". 17 articles were selected. In conclusion, from the incorporation of immunotherapy in the SUS, a considerable increase in survival is estimated. However, the lack of budget availability delays the implementation of the treatment. Furthermore, more research and new ways of selecting patients are needed for the availability of treatment in order not to harm the public system.

Autoimunidade em pacientes com endometriose: associação clinicolaboratorial / Autoimmunity in patients with endometriosis: clinical-laboratory association

A endometriose é condição ginecológica crônica, caracterizada pela presença de tecido semelhante ao endométrio fora da cavidade uterina. Apesar da causa ser complexa e pouco elucidada, estudos sugerem fortes associações entre endometriose e anormalidades no sistema imunológico. Assim é importante determinar a prevalência de fator anti nuclear (FAN) e anti-DNA em pacientes diagnosticadas com endometriose e suas associações. Foi realizado estudo transversal analítico para elucidar o tema. A amostra foi composta por 94 pacientes com diagnóstico de endometriose confirmado por videolaparoscopia e biópsia com estudo anatomopatológico. Como grupo controle foram utilizados 91 pacientes pareados em idade e gênero. Em conclusão, pacientes com endometriose apresentam maior prevalência de FAN em relação ao grupo controle. A positividade do FAN não tem associação com o estadiamento ASRM da endometriose e gravidade da doença. As pacientes com endometriose não apresentaram reatividade para o anticorpo anti-ds-DNA.

Endometriosis is a chronic gynecological condition, characterized by the presence of tissue similar to the endometrium outside the uterine cavity. Although the etiology is complex and poorly understood, studies suggest strong associations between endometriosis and abnormalities in the immune system. Thus, it is important to determine the prevalence of anti-nuclear factor (ANA) and anti-DNA in patients diagnosed with endometriosis and their associations. An analytical cross-sectional study was carried out to elucidate the topic. The sample consisted of 94 patients with a diagnosis of endometriosis confirmed by videolaparoscopy and biopsy with anatomopathological study. As a control group, 91 patients matched for age and gender were used. In conclusion, patients with endometriosis have a higher prevalence of ANA compared to the control group. ANA positivity is not associated with ASRM staging of endometriosis and disease severity. Patients with endometriosis did not show reactivity to anti-ds-DNA antibody.

O que o profissional da saúde precisa saber a respeito do atendimento às pessoas transexuais ou transgênero / What does the health professional needs to know about the care of transgender people

RESUMO: Introdução: As pessoas transexuais encontram uma série de dificuldades no atendimento médico, tanto na rede privada como na pública no Brasil. Objetivo: Demonstrar aos profissionais da área da saúde a realidade vivida pelas pessoas transexuais, quando necessitam de atendimento médico no Brasil, visando aprimorar os conhecimentos sobre o atendimento a este grupo populacional. Métodos: Coleta de dados realizada em fevereiro de 2020 com buscas nas bases eletrônicas: PubMed, Scielo, Lilacs e Google Scholar. Utilizou-se os descritores em associação: transgender; medical care; transexual; cross-sex hormone therapy, no período entre 2000 a 2020. Resultados: Encontramos 720 publicações com as palavras-chave transgender persons e medical care, 30 com as palavras-chave transgender, medical care e cross-sex hormone therapy, sendo escassos os estudos feitos no Brasil. Conclusão: Para que ocorra uma melhora no atendimento à saúde das pessoas transexuais é necessário que sejam inseridas disciplinas específicas sobre este tema na grade curricular dos cursos técnicos, de graduação e de pós-graduação da área da saúde. (AU)

ABSTRACT: Introduction: Transsexual people encounter a series of difficulties in medical care, both in the private and public health systems in Brazil. Objectives: Demonstrate to health professionals the reality experienced by transsexual people when they need medical care in Brazil, in order to improve knowledge about the care of this population group. Methods: Data collection was carried out in February 2020 with searches in electronic databases: Pubmed, Scielo, Lilacs and Google Scholar. The following descriptors were used: transgender; medical care; transsexual; cross-sex hormone therapy from 2000 to 2020.Results: We found 720 publications with the keywords transgender persons and medical care, 30 with the keywords transgender, medical care and cross-sex hormone therapy, with few studies conducted in Brazil Conclusion: To improve the health care of transgender people, it is necessary to insert specific disciplines on this topic in the curriculum of technical, undergraduate and graduate courses in the health area. (AU)

First Report of CR1 Polymorphisms and Soluble CR1 Levels Associated with Late Onset Alzheimer's Disease (LOAD) in Latin America.

The CR1 gene has been widely studied in Alzheimer's disease (AD), since its first association with the disease in 2009. Even after 11 years of this discovery, the role of this gene in AD has not yet been fully elucidated and the association of its variants was not validated in Latin American populations. We genotyped five CR1 single nucleotide polymorphisms (SNPs rs6656401, rs3849266, rs2274567, rs4844610, and rs12034383) in up to 162 AD patients and 137 controls through PCR-SSP and iPLEX MassARRAY Platform (Sequenom), and measured soluble CR1 (sCR1) levels in plasma of 40 AD patients and 39 controls with an enzyme-linked immunosorbent assay (ELISA). Homozygosity for haplotype rs3849266*C_rs2274567*A (CA/CA genotype) was associated with susceptibility to AD (OR = 2.94, p = 0.018). Patients presented higher sCR1 levels in plasma than controls (p = 0.038). Furthermore, patients that carry the rs2274567*G allele (p.1208Arg) presented higher sCR1 levels than A/A (p.1208His/His) homozygotes (p = 0.036). This is the first study to validate the association of CR1 polymorphisms with late-onset Alzheimer's disease, as well as to evaluate sCR1 levels in a Latin American population. SNPs present in the regulatory and coding regions of this gene may be playing a key role in the observed association, probably by interfering in Aß plaques clearance. Inhibition may be due to the increase in local sCR1 levels observed in patients, which may result from polymorphisms leading to larger isoforms of CR1 and/or structural alterations of the protein that makes it less functional, as well as increased vesiculation of the molecules.

Comparação de eficácia entre as sondas monocanalicular e bicanalicular no tratamento da obstrução congênita das vias lacrimais / Efficacy of monocanalicular versus bicanalicular intubation in the treatment of congenital nasolacrimal duct obstruction

Resumo Objetivo: Avaliar e comparar a taxa de sucesso da intubação monocanalicular ou bicanalicular em pacientes com obstrução congênita do ducto lacrimonasal (OCDLN), levando-se em consideração a taxa de sucesso, a dificuldade do procedimento e o custo dos tubos. Métodos: Foram analisados retrospectivamente 54 prontuários, totalizando 58 vias lacrimais com diagnóstico de OCDLN, que realizaram intubação das vias lacrimais monocanalicular ou bicanalicular com tubos de silicone. Anamnese, exame oftalmológico geral, testes específicos, como o Teste do Desaparecimento do Corante (TDC) e Teste de Observação de Fluoresceína na Orofaringe (TOFO), e, caso necessário, exames complementares como a dacriocistografia, foram utilizados para diagnóstico e inclusão na pesquisa. Foram tratados com intubação os pacientes sem resposta adequada ao tratamento prévio, ou seja, que permaneceram com sintomas de secreção e epífora contínua após a realização de massagem de Crigler e sondagem. Resultados: A intubação monocanalicular foi realizada em 27 vias lacrimais e a intubação bicanalicular, em 31 vias lacrimais. A taxa de sucesso foi alta em ambos os métodos, com melhora em 26 (96,3%) vias lacrimais com sonda monocanalicular e em 30 (96,8%), com sonda bicanalicular (p=0,718). As duas técnicas apresentaram 100% de sucesso nos pacientes com até 2 anos e acima de 4 anos de idade (p=1). A taxa de sucesso entre os 2 e 4 anos de idade foi de 91,5% para as monocanaliculares e 87,5% para as bicanaliculares, (p=0,652). Conclusão: o presente estudo não mostrou diferença significativa no sucesso da intubação quando utilizando sondas mono ou bicanaliculares. A intubação monocanalicular mostrou-se de mais fácil execução, ao passo que o tubo bicanalicular possui menor custo.

Abstract Objective: to evaluate and to compare the success rate of monocanalicular or bicanalicular intubation in congenital nasolacrimal duct obstruction (CNDO) carriers in terms of success rate, difficulty of the procedure, and cost of the tubes. Methods: fifty-four CNDO carriers with 58 obstructed lacrimal vies (LV) who were submitted to lacrimal system intubation using mono or bicanalicular stent had their medical records analyzed. A clinical history, a general ophthalmologic examination, specific tests such as the fluorescein dye disappearance test (FDDT) and observation test of fluorescein in the oropharynx (OTFO) were used for diagnosis and inclusion in the study. Patients who continued exhibiting discharge and continuous epiphora after previous treatment, Crigler massage and probing, were treated surgically with intubation. Results: Monocanalicular intubation was performed on 27 LV and bicanalicular intubation was performed on 31 LV. High success rates were observed, with improvement in 26 (96.3%) with monocanalicular intubation and in 30 LV (96.8%) with bicanalicular intubation (p=0.718). Furthermore, both techniques were 100% successful in patients up to 2 and over 4 years of age (p=1). The success rates between 2-4 years of age were 91.6% in monocanalicular intubation and 87.5% in bicanalicular intubation (p=0.652). Conclusion: The success rate using monocanalicular or bicanalicular intubation to treat CNDO had no significant difference in the studied children. Furthermore, the monocanalicular tube was easier to use, while the bicanalicular tube had a lower cost.

Complement Receptor 1 (CR1, CD35) Polymorphisms and Soluble CR1: A Proposed Anti-inflammatory Role to Quench the Fire of "Fogo Selvagem" Pemphigus Foliaceus.

Pemphigus foliaceus is an autoimmune disease that is sporadic around the world but endemic in Brazil, where it is known as fogo selvagem (FS). Characterized by autoantibodies against the desmosomal cadherin desmoglein 1, FS causes painful erosions, and crusts that may be widespread. The recognition of antigens, including exposed sugar moieties, activates the complement system. Complement receptor 1 (CR1, CD35), which is responsible for the Knops blood group on erythrocytes (York and McCoy antigens), is also expressed by antigen-presenting cells. This regulates the complement system by removing opsonized antigens, blocking the final steps of the complement cascade. Membrane-bound CR1 also fosters antigen presentation to B cells, whereas soluble CR1 has anti-inflammatory properties. CR1 gene polymorphisms have been associated with susceptibility to complex diseases. In order to investigate the association of CR1 polymorphisms with FS susceptibility, we developed a multiplex sequence-specific assay to haplotype eleven polymorphisms in up to 367 FS patients and 242 controls from an endemic area and 289 from a non-endemic area. We also measured soluble CR1 (sCR1) in the serum of 53 FS patients and 27 controls and mRNA levels in the peripheral blood mononuclear cells of 63 genotyped controls. The haplotypes CR1*3B2B (with the York antigen-encoded by p.1408Met) and CR1*3A2A (with p.1208Arg) were associated with protection against FS (OR = 0.57, P = 0.027, and OR = 0.46, P = 0.014, respectively). In contrast, the CR1*1 haplotype (with the McCoy antigen - encoded by p.1590Glu) was associated with FS susceptibility (OR = 4.97, P < 0.001). Heterozygote rs12034383*A/G individuals presented higher mRNA expression than homozygotes with the G allele (P = 0.04). The lowest sCR1 levels occurred in patients with active disease before treatment (P = 0.036). Patients in remission had higher levels of sCR1 than did healthy controls (P = 0.013). Among those under treatment, patients with localized lesions also presented higher sCR1 levels than those with generalized lesions (P = 0.0073). In conclusion, the Knops blood group seems to modulate susceptibility to the disease. Furthermore, corticosteroid treatment might increase sCR1 serum levels, and higher levels may play an anti-inflammatory role in patients with FS, limiting the distribution of lesions. Based on these results, we suggest CR1 as a potential new therapeutic target for the treatment of FS.

Fibromyalgia, sleep disturbance and menopause: Is there a relationship? A literature review.

INTRODUCTION: Fibromyalgia (FM) symptoms worsen in a significant portion of patients with the onset of menopause. Some patients report that their symptoms begin after menopause, suggesting a relationship between these entities. Sleep disturbance is a common condition in FM and menopause, and it is associated with chronic pain. METHODS/OBJECTIVES: Several electronic databases were searched, from the first available year to April 2018 to evaluate the publications that assessed the effects of menopause and sleep disturbance on the appearance or worsening of FM and the role of hormone therapy for these patients. RESULTS: The results are summarized in three tables. The objective sleep patterns of FM patients included high sleep latency, frequent arousals and intrusion of alpha wave sleep and NREM (non-rapid eye movement) sleep in delta sleep. Poor sleep during menopause is more frequent in late perimenopause and surgical menopause, and may be related to vasomotor symptoms or not. Hormone therapy exerted a positive effect on subjective sleep quality of symptomatic menopausal women. Studies have shown a high association between FM and early and surgical menopause. Raloxifene exerted a positive effect on pain and sleep in FM patients; however one study that analyzed the effects of transdermal estrogen therapy found no improvement in subjective and objective parameters of pain. CONCLUSION: Further studies are needed to elucidate the nature of the association between menopause, sleep and persistent pain syndromes, such as FM, showing the role of hormone therapy in prospective placebo-controlled trials.

Complement receptor 1 (CR1, CD35) association with susceptibility to leprosy.

BACKGROUND: Pathophysiological mechanisms are still incompletely understood for leprosy, an urgent public health issue in Brazil. Complement receptor 1 (CR1) binds complement fragments C3b/C4b deposited on mycobacteria, mediating its entrance in macrophages. We investigated CR1 polymorphisms, gene expression and soluble CR1 levels in a case-control study with Brazilian leprosy patients, aiming to understand the role of this receptor in differential susceptibility to the disease. METHODOLOGY: Nine polymorphisms were haplotyped by multiplex PCR-SSP in 213 leprosy patients (47% multibacillary) and 297 controls. mRNA levels were measured by qPCR and sCR1 by ELISA, in up to 80 samples. PRINCIPAL FINDINGS: Individuals with the most common recombinant haplotype harboring rs3849266*T in intron 21 and rs3737002*T in exon 26 (encoding p.1408Met of the York Yka+ antigen), presented twice higher susceptibility to leprosy (OR = 2.43, p = 0.017). Paucibacillary patients with these variants presented lower sCR1 levels, thus reducing the anti-inflammatory response (p = 0.040 and p = 0.046, respectively). Furthermore, the most ancient haplotype increased susceptibility to the multibacillary clinical form (OR = 3.04, p = 0.01) and presented the intronic rs12034383*G allele, which was associated with higher gene expression (p = 0.043), probably increasing internalization of the parasite. Furthermore, there was an inverse correlation between the levels of sCR1 and mannose-binding lectin (initiator molecule of the lectin pathway of complement, recognized by CR1) (R = -0.52, p = 0.007). CONCLUSIONS: The results lead us to suggest a regulatory role for CR1 polymorphisms on mRNA and sCR1 levels, with haplotype-specific effects increasing susceptibility to leprosy, probably by enhancing parasite phagocytosis and inflammation.

Complement activation in acute myocardial infarction: An early marker of inflammation and tissue injury?

BACKGROUND: Acute myocardial infarction (AMI) is a potentially fatal condition, being a major cause of death worldwide. Ischemia suffered during AMI causes tissue damage, leading to an inflammatory process. Moreover, myocardial injury can generate damage-associated molecular patterns that activate pattern recognition molecules including some complement proteins. METHODS: Here we investigated products of complement activation, C3d and soluble C5b9 (sC5b9), as potential biomarkers for myocardial injury and inflammation, as well as serum cytokines (IL-6 and TNF-alpha), alpha-1-acid glycoprotein (AGP), and classical markers of myocardial necrosis (creatine kinase, creatine kinase-MB isoform, myoglobin and troponin-I) in a longitudinal study of patients with AMI (from admission, 6 h and 12 h post admission, and at discharge from hospital). Individuals undergoing cardiac catheterization (CC) with normal coronary arteries and asymptomatics with no history of cardiovascular disease or invasive procedures were included as controls. RESULTS: Plasma C3d was higher in AMI at admission, 6 h, 12 h, and discharge vs CC (p < 0.0001; p = 0.0061; p = 0.0081; p = 0.044) and asymptomatic (p = 0.0001 for admission, 6 h and 12 h; p = 0.0002 for discharge). Moreover, sC5b9 was higher only at admission and 6 h vs asymptomatic (p = 0.0031 and p = 0.0019). Additionally, AGP levels were elevated at admission, 6 h, 12 h, and discharge vs asymptomatic (p = 0.0003; p = 0.0289; p = 0.0009, p = 0.0017). IL-6 concentration was low at admission and 6 h and reached a peak at 12 h (p < 0.0001 for all groups). All classical markers of myocardial necrosis presented higher concentration at 6 h. CONCLUSIONS: Our results showed that complement activation is an early event in AMI occurring before the elevation of classical markers of myocardial necrosis such as creatine kinase, creatine kinase-MB isoform, myoglobin and troponin-I. These findings indicated C3d and sC5b9 as possible biomarkers for inflammation and tissue damage in AMI.

Judicial demand of medications through the Federal Justice of the State of Paraná.

OBJECTIVE: To describe the profile of lawsuits related to drug requests filled at the Federal Justice of the State of Paraná. METHODS: A cross-sectional study, and the data were obtained through consulting the lawsuits at the online system of the Federal Justice of Paraná. RESULTS: Out of 347 lawsuits included in the study, 55% of plaintiffs were women, with a median age of 56 years. Oncology was the field with more requests (23.6%), and the highest mean costs. A wide variety of diseases and broad variety of requested drugs were found in the lawsuits. Approximately two-thirds of them were requested by the brand name, and the most often requested drugs were palivizumab and tiotropium bromide. Only 14.5% of the requested medicines were registered in the National Medication Register. The Public Defender's Office filled actions in 89.6% of cases and all lawsuits had an interim relief. The mean time for approval was 35 days and 70% of requests were granted. CONCLUSION: Oncology was the field with the highest demand for medicines at the Federal Justice of Paraná in 2014. A great variety of medications was requested. The Public Defender´s Office represented most lawsuits. All demands had an interim relief, and the majority of requests were granted, within an average of 35 days. OBJETIVO: Descrever o perfil das ações que solicitam medicamentos ajuizadas na Justiça Federal do Paraná. MÉTODOS: Estudo transversal descritivo, cujos dados foram obtidos por meio de consulta aos processos no sistema on-line da Justiça Federal do Paraná. RESULTADOS: Dentre os 347 processos incluídos no estudo, 55% dos autores eram mulheres, com mediana da idade de 56 anos, sendo a área mais procurada a oncologia (23,6%). A área oncológica também foi a que apresentou maiores custos médios. Foi ampla a variedade de doenças geradoras das ações e também foi consequentemente grande a variedade de medicamentos solicitados. Cerca de dois terços dos fármacos foram solicitados pelo nome comercial, e os mais requeridos foram o palivizumabe e brometo de tiotrópio. Apenas 14,5% dos medicamentos solicitados estavam cadastrados no Registro Nacional de Medicamentos. A Defensoria Pública impetrou as ações em 89,6% dos casos. Todos os processos pediam antecipação de tutela do medicamento. O tempo médio para deferimento foi de 35 dias, sendo que 70% dos pedidos foram deferidos. CONCLUSÃO: A área com maior número de casos de demanda de medicamentos na Justiça Federal do Paraná no ano de 2014 foi de Oncologia. Observou-se grande variedade de medicamentos solicitados. A maioria das ações foi impetrada pela Defensoria Pública. Todas as demandas exigiram antecipação de tutela, sendo que a maioria dos pedidos foram deferidos, num prazo médio de 35 dias.

Judicial demand of medications through the Federal Justice of the State of Paraná / Demanda judicial de medicamentos na Justiça Federal do Estado do Paraná

ABSTRACT Objective To describe the profile of lawsuits related to drug requests filled at the Federal Justice of the State of Paraná. Methods A cross-sectional study, and the data were obtained through consulting the lawsuits at the online system of the Federal Justice of Paraná. Results Out of 347 lawsuits included in the study, 55% of plaintiffs were women, with a median age of 56 years. Oncology was the field with more requests (23.6%), and the highest mean costs. A wide variety of diseases and broad variety of requested drugs were found in the lawsuits. Approximately two-thirds of them were requested by the brand name, and the most often requested drugs were palivizumab and tiotropium bromide. Only 14.5% of the requested medicines were registered in the National Medication Register. The Public Defender’s Office filled actions in 89.6% of cases and all lawsuits had an interim relief. The mean time for approval was 35 days and 70% of requests were granted. Conclusion Oncology was the field with the highest demand for medicines at the Federal Justice of Paraná in 2014. A great variety of medications was requested. The Public Defender´s Office represented most lawsuits. All demands had an interim relief, and the majority of requests were granted, within an average of 35 days.

RESUMO Objetivo Descrever o perfil das ações que solicitam medicamentos ajuizadas na Justiça Federal do Paraná. Métodos Estudo transversal descritivo, cujos dados foram obtidos por meio de consulta aos processos no sistema on-line da Justiça Federal do Paraná. Resultados Dentre os 347 processos incluídos no estudo, 55% dos autores eram mulheres, com mediana da idade de 56 anos, sendo a área mais procurada a oncologia (23,6%). A área oncológica também foi a que apresentou maiores custos médios. Foi ampla a variedade de doenças geradoras das ações e também foi consequentemente grande a variedade de medicamentos solicitados. Cerca de dois terços dos fármacos foram solicitados pelo nome comercial, e os mais requeridos foram o palivizumabe e brometo de tiotrópio. Apenas 14,5% dos medicamentos solicitados estavam cadastrados no Registro Nacional de Medicamentos. A Defensoria Pública impetrou as ações em 89,6% dos casos. Todos os processos pediam antecipação de tutela do medicamento. O tempo médio para deferimento foi de 35 dias, sendo que 70% dos pedidos foram deferidos. Conclusão A área com maior número de casos de demanda de medicamentos na Justiça Federal do Paraná no ano de 2014 foi de Oncologia. Observou-se grande variedade de medicamentos solicitados. A maioria das ações foi impetrada pela Defensoria Pública. Todas as demandas exigiram antecipação de tutela, sendo que a maioria dos pedidos foram deferidos, num prazo médio de 35 dias.