Resumen: La vasculitis reumatoidea es una complicación sistémica y poco frecuente de la Artritis Reumatoidea. Si bien su incidencia ha descendido en los últimos años con el advenimiento de las nuevas terapias inmunosupresoras y biológicas, continua teniendo una alta morbimortalidad. Predomina en el sexo masculino, en pacientes seropositivos y con un largo período de la enfermedad establecida. Requiere de alta presunción diagnostica, siendo el compromiso cutáneo y nervioso periférico el más frecuente. La biopsia de nervio o piel es requerida habitualmente para su diagnóstico. El tratamiento se basa en corticoides e inmunosupresores. Presentamos tres casos clínicos y realizamos una revisión de la literatura.

Abstract: Rheumatoid vasculitis is a rare systemic complication of rheumatoid arthritis. Although its incidence has decreased in recent years with the advent of new immunosuppressive and biological therapies, it continues to have a high morbidity and mortality. It predominates in males, in seropositive patients and with a long period of established disease. It requires high diagnostic presumption, with skin and peripheral nervous involvement being the most affected. Nerve or skin biopsy is usually required for diagnosis. Treatment is based on corticosteroids and immunosuppressants. We present three clinical cases and carry out a review of the literature.

Resumo: A vasculite reumatóide é uma complicação sistêmica rara da artrite reumatóide. Embora sua incidência tenha diminuído nos últimos anos com o advento de novas terapias imunossupressoras e biológicas, continua apresentando elevada morbidade e mortalidade. Predomina no sexo masculino, em pacientes soropositivos e com longo período de doença estabelecida. Exige alta presunção diagnóstica, sendo o envolvimento cutâneo e nervoso periférico os mais afetados. A biópsia de nervo ou pele geralmente é necessária para o diagnóstico. O tratamento é baseado em corticosteroides e imunossupressores. Apresentamos três casos clínicos e realizamos uma revisão da literatura.

The management of rheumatoid arthritis (RA) requires early diagnosis and prompt initiation of therapy, together with lifestyle interventions, particularly smoking cessation. These guidelines recommend a treat-to-target strategy using a composite disease activity score at each visit, with frequent follow-up and escalation or switching of disease-modifying antirheumatic drug (DMARD) therapy until the goal of low disease activity is achieved. A stepwise algorithm for DMARD therapy is provided. Screening for comorbidities and vaccination is advised.

Abstract Aim: To analyse the cases of bilateral vocal fold paralysis (BVFP) diagnosed by the ENT department at Hospital Garcia de Orta. To emphasize rare causes of this entity and its treatment. Study design: Retrospective study of BVFP cases diagnosed between January 2011 and December 2022. Materials and methods: Inclusion criteria: diagnosis of BVFP by an ENT with videonasolaryngoscopy documentation. Patients with pharyngolaryngeal neoplasia and insufficient records were excluded. Results: 109 patients were diagnosed with BVFP. The mean age at diagnosis time was 67 years. The presenting symptoms were: acute high dyspnoea in 92.7%, dysphonia in 19.3% and dysphagia in 7.3%. Rare causes were diagnosed: degenerative neurological diseases, neoplasms (thymus, oesophagus, lung, central nervous system), newly brain metastasis, hypocalcaemia, hypothyroidism, neurosyphilis, acute hepatitis B, meningitis and rheumatoid arthritis. 78% patients were approached surgically: tracheostomy, posterior cordotomy using LASER® and vocal cord lateralization. Conclusions: The etiological investigation with imaging exams and analytical evaluation allowed the diagnosis of rare causes of BVFP. In some cases, correction of the underlying cause has allowed reversion of vocal fold paralysis.

Resumo Objetivos: Analisar os casos de paralisia bilateral das cordas vocais (PBCV) diagnosticados no serviço de Otorrinolaringologia do Hospital Garcia de Orta. Alertar para causas raras desta entidade e seu tratamento. Desenho do estudo: Estudo retrospetivo dos casos de PBCV diagnosticados entre janeiro de 2011 e dezembro de 2022. Materiais e Métodos: Critérios de inclusão: diagnóstico de PBCV, observação por otorrinolaringologia com documentação por vídeo nasofaringolaringoscopia. Foram excluídos os doentes com neoplasia faringolaríngea e registos insuficientes. Resultados: Foram diagnosticados 109 doentes com PBCV. A idade média à data de diagnóstico foi de 67 anos. Os sintomas de apresentação foram: dispneia alta aguda em 92,7%, disfonia em 19,3% e disfagia em 7,3%. Foram diagnosticadas causas raras: Doenças neurológicas degenerativas, neoplasias (timo, esófago, pulmão, sistema nervoso central), metastização cerebral de novo, hipocalcemia, hipotiroidismo, neurossífilis, hepatite B aguda, meningite e artrite reumatóide. 78% dos doentes foram abordados cirurgicamente: através de traqueostomia, cordotomia posterior com recurso a LASER® e lateralização de corda vocal de Lichtenberger. Conclusões: A investigação etiológica com recurso a avaliação analítica e imagiológica permitiu o diagnóstico de causas raras de PBCV. Em alguns casos, a correção da causa subjacente permitiu a reversão da paralisia das cordas vocais.

RESUMEN La subluxación atlantoaxial es la lesión más frecuente en la columna cervical causada por la artritis reumatoidea. Se manifiesta por rigidez de nuca, dolor cervical y déficit neurológico. El diagnóstico se realiza con tomografía computarizada e imágenes de resonancia magnética. El intervalo atlanto dental anterior mayor a 5mm indica inestabilidad atlantoaxial, el intervalo atlanto dental posterior menor a 14mm advierte riesgo neurológico. Las indicaciones más frecuentes de cirugía son: dolor cervical severo, inestabilidad y síntomas de mielopatía. Cuando existe compresión medular es necesaria la descompresión cervical alta sea por vía posterior o por vía anterior (odontoidectomía endonasal versus transoral). La línea rinopalatina nos indicará la factibilidad de una odontoidectomía endonasal endoscópica (OEE). El objetivo de la presentación del presente caso es compartir nuestra experiencia con la primera odontoidectomía endonasal endoscópica realizada en nuestro país y fomentar la utilización de la técnica. La cirugía fue realizada en un paciente con cuadriparesia espástica por subluxación atlantoaxial por artritis reumatoidea y que presentó excelente evolución pos operatoria, con recuperación casi completa. La OEE es una técnica operatoria mínimamente invasiva, ideal para pacientes con múltiples comorbilidades y que ofrece de buenos a excelentes resultados.

ABSTRACT Atlantoaxial subluxation is the most common injury to the cervical spine caused by rheumatoid arthritis. It is manifested by neck stiffness, neck pain and neurological deficit. Diagnosis is made with computed tomography and magnetic resonance imaging. The anterior dental atlanto interval greater than 5mm indicates atlantoaxial instability, the posterior dental atlanto interval less than 14mm warns of neurological risk. The most frequent indications for surgery are: severe neck pain, instability and symptoms of myelopathy. When there is spinal cord compression, upper cervical decompression is necessary, either via a posterior or anterior approach (endonasal versus transoral odontoidectomy). The rhinopalatine line will indicate the feasibility of an endoscopic endonasal odontoidectomy (EEO). The objective of the presentation of this case is to share our experience with the first endoscopic endonasal odontoidectomy performed in our country and to promote the use of the technique. The surgery was performed on a patient with spastic quadriparesis due to atlantoaxial subluxation due to rheumatoid arthritis and who presented excellent postoperative evolution, with almost complete recovery. EEO is a minimally invasive surgical technique, ideal for patients with multiple comorbidities and offering good to excellent results.

RESUMEN Objetivo: Determinar las características clínicas y epidemiológicas de los pacientes con uveítis no infecciosas que acuden a un hospital universitario de Paraguay. Metodología: Se realizó un estudio observacional, descriptivo de corte transversal, retrospectivo. Se incluyeron casos consecutivos de pacientes que acudieron al Servicio de Oftalmología del Hospital de Clínicas de enero del 2020 a octubre del 2021 y que fueron diagnosticados con uveítis no infecciosa. Las variables estudiadas fueron sexo, edad, procedencia, motivo de consulta, clasificación anatómica, curso clínico, asociación sistémica y ocular y bilateralidad. Resultados: Se revisó los expedientes de 78 pacientes, el 66,7% fue de sexo femenino y 42 pacientes (53,8%) procedían del departamento Central. La localización anatómica anterior de la uveítis fue la más frecuente (53,9%), seguida en orden decreciente por la panuveítis, la posterior y la intermedia. Respecto a las uveítis anteriores, en 24 pacientes (57,1%) fueron unilaterales, en 40 (95,2%) no granulomatosas, 19 (45,2%) presentaron un curso clínico agudo, el motivo de consulta más frecuente fue “ojo rojo y doloroso” con 15 pacientes (35,7%), la asociación sistémica más frecuente fue HLA- B27+ en 16 pacientes (38,1%). En cuanto, a las panuveítis, 13 pacientes (50%) se asociaron con síndrome de Vogt-Koyanagi-Harada y de las posteriores 2 pacientes relacionados a Artritis reumatoidea. Conclusión: El patrón clínico y epidemiológico observado en este estudio es en su mayor parte similar al observado en la mayoría de las series encontradas en la literatura. Llaman la atención en este estudio que las asociaciones más frecuentes son diferentes de los reportados en la literatura: de la anterior, el HLA-B27+; de la posterior, la artritis reumatoidea; y que entre las panuveítis se observa un gran porcentaje de síndrome de Vogt-Koyanagi-Harada.

ABSTRACT Objective: To determine the clinical and epidemiological characteristics of patients with noninfectious uveitis at a university hospital in Paraguay. Methodology: An observational, descriptive, cross-sectional, retrospective study was performed. Consecutive patients who attended the Ophthalmology Service of the Hospital de Clínicas from January 2020 to October 2021 and who were diagnosed with non-infectious uveitis were included. The variables studied were sex, age, origin, reason for consultation, anatomical classification, clinical course, systemic and ocular associations, and bilaterality. Results: A total of 78 medical records of patients meeting the inclusion and exclusion criteria were analyzed. Of the patients, 66.7% were female and 42 (53.8%) were from the Central Department. The anterior anatomical location of uveitis was the most frequent (53.9%), followed in decreasing order by panuveitis, posterior uveitis, and intermediate uveitis. Regarding anterior uveitis, 24 patients (57.1%) had unilateral uveitis, 40 (95.2%) were non-granulomatous, 19 (45.2%) presented an acute clinical course, the most frequent reason for consultation was "red and painful eye" with 15 patients (35.7%), the most frequent systemic association was HLA- B27+ in 16 patients (38.1%). As for panuveitis, 13 patients (50%) were associated with Vogt-Koyanagi-Harada syndrome, and of the latter, two patients were related to rheumatoid arthritis. Conclusion: The clinical and epidemiological patterns observed in this study were largely consistent with those reported in the literature. Notably, the most frequent associations differed from those reported in the literature: HLA-B27+ for anterior uveitis, rheumatoid arthritis for posterior uveitis, and a significant percentage of Vogt-Koyanagi-Harada syndrome among panuveitis cases.

Resumen: Introducción : La artritis reumatoide (AR) es una enfermedad inflamatoria crónica, autoinmune, caracterizada por poliartritis crónica, aditiva, simétrica, que puede cursar con manifestaciones extraarticulares (MExA) asociadas a una mayor morbimortalidad. Objetivo: de describir las MExA más frecuentes en AR. Métodos: se realizó un estudio descriptivo, transversal y retrospectivo de revisión de historias clínicas de pacientes diagnosticados con AR, durante el periodo diciembre 2011-enero 2022. Resultados: Participaron 150 pacientes con AR, con una edad promedio de 53,7±12,5 años, el sexo predominante fue el femenino con 84,6%, el tiempo de evolución de la AR fue de 7,2±8,9 años; en cuanto a las características serológicas, 91,1% tenía Factor reumatoideo positivo y 76,9% tenía anticuerpos contra péptidos cíclicos citrulinados positivo. Tanto al ingreso, como en la última consulta los pacientes presentaron alguna manifestación extraarticular (MExA), 61,3% y 70%, respectivamente, siendo las más frecuentes la anemia de los trastornos crónicos (al ingreso 44,6% y en última consulta 50,6%), seguida de nódulos reumatoideos (al ingreso con 8% y en la última consulta 9,3%). Conclusiones: Las MExA se presentaron en 70% de los pacientes, siendo las más frecuentes la anemia y los nódulos reumatoideos. Estos datos muestras los cambios que han tenido la frecuencia de estas MExA en esta enfermedad a través del tiempo.

Abstract: Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory, autoimmune disease, characterized by chronic, additive, symmetrical polyarthritis, which can present with extra-articular manifestations (ExAM), associated with greater morbidity and mortality. Objective: to describe the most frequent ExAM in RA. Methods: a descriptive, cross-sectional and retrospective study was carried out to review the medical records of patients diagnosed with RA, during the period December 2011-January 2022. Results: 150 patients with RA participated, with an average age of 53.7±12.5 years, the predominant sex was female with 84.6%, the evolution time of RA was 7.2±8.9. years; Regarding serological characteristics, 91.1% had positive Rheumatoid Factor and 76.9% had positive antibodies against cyclic citrullinated peptides. Both upon admission and at the last consultation, patients presented some extra-articular manifestation (ExAM), 61.3% and 70%, respectively, with the most frequent being chronic anemia (at admission 44.6% and at last consultation 50.6%), followed by rheumatoid nodules (at admission with 8% and at the last consultation 9.3%). Conclusions: ExAM occurred in 70% of patients, the most frequent being anemia and rheumatoid nodules. These data show the changes in the frequency of ExAM in the disease over time.

Abstract Rheumatoid arthritis is among the most prevalent connective tissue illnesses worldwide wich usually affects diarthrodial joints symmetrically, however, it can be associated with more severe systemic symptoms and a worse prognosis. The lungs are usually one of the most affected organs, where it can affect intersticial tissue, the pleura, airways and vascular structures where among these is very important interstitial involvement is very important among there since it can present as the first manifestation of the disease with great morbidity and being one of the main causes of death in patients with rheumatoid arthritis, survival has been estimated to range between three and seven years after diagnosis. We present the case of a 66 years old patient with a history of rheumatoid arthritis, heart failure and mitral valve replacement on anticoagulant treatment with dicoumarins because of a mitral valve replacement, admitted to an internment with a diagnosis of pneumonia vs. alveolar hemorrhage (chest CT with bilateral mixed infiltrations) that progressed unfavorably, so she was delivered to critical care with mechanical ventilation requirement. Due to the characteristics of the images, laboratory and bacteriology results, it was interpreted as interstitial lung disease associated with rheumatoid arthritis, treatment with corticosteroids was initiated and the patient progressed favorably. The importance of early diagnosis of this disease lies in the fact that timely treatment can save the lives of patients who suffer from it.

Resumen La artritis reumatoidea es una de las enfermedades del tejido conectivo más prevalentes a nivel mundial, y suele afectar especialmente en forma simétrica las articulaciones diartrodiales; en algunas ocasiones puede asociarse con manifestaciones en otros órganos de la economía, con el consiguiente aumento de la morbimortalidad. El pulmón suele ser uno de los órganos más comprometidos, por lo que es de vital importancia determinar el compromiso intersticial dada la alta mortalidad asociada. Puede incluso presentarse como primera manifestación de la enfermedad o como un cuadro de insuficiencia respiratoria grave, por lo que es de suma importancia considerarlo dentro de los diagnósticos diferenciales, dado que un retraso en su diagnóstico, y por tanto en el tratamiento correcto, puede ocasionar la muerte del paciente. Presentamos el caso de una paciente de 66 años, con antecedentes de artritis reumatoidea, insuficiencia cardíaca y reemplazo valvular mitral, en tratamiento con dicumarínicos, que se encuentra cursando una internación en clínica médica por disnea clase funcional III, con diagnósticos presuntivos de neumonía y hemorragia alveolar que evolucionó con requerimiento de ventilación mecánica invasiva. Debido a las características de las imágenes, la ausencia de leucocitosis, neutrofilia y aislamiento bacteriológico en cultivos, se descartó patología infecciosa, y al no comprobarse presencia de sangre en la vía aérea mediante fibrobroncoscopia, se planteó el diagnóstico de enfermedad pulmonar intersticial y se inició el tratamiento con corticosteroides con respuesta favorable, por lo que se la desvinculó del ventilador sin complicaciones, al quinto día de iniciado el tratamiento.

ABSTRACT Introduction: rheumatoid arthritis is an autoimmune disease with articular and extra-articular involvement. It is considered late-onset when it begins after age 60 and has its own distinctive characteristics. Objective: to analyze the demographic, clinical and treatment characteristics of late-onset rheumatoid arthritis. Methods: automated documentary review in the PubMed/Medline and Scielo databases (Google Scholar was used as a search engine) in the period between January and June 2023. 24 articles were selected, 75% updated. Results: there is a 1:1 relationship between sexes, with three fundamental forms of presentation of the disease. The clinical characteristics are heterogeneous, with greater involvement of large joints, more constitutional symptoms, stiffness and extra-articular manifestations mostly of a cardiorespiratory nature, as well as less seropositivity. The prognosis depends mainly on age, comorbidities, seropositivity and the type of treatment; which is worse than in younger patients. Therapeutic management has the same objectives as in early-onset disease and there is a tendency towards less intensive treatments with antirheumatic drugs. Conclusions: late-onset rheumatoid arthritis has particular characteristics that must be taken into account for accurate and early diagnosis, adequate therapeutic management and control of possible adverse effects and good adherence to treatment.

RESUMEN Introducción: la artritis reumatoide es una enfermedad autoinmune con afectación articular y extraarticular. Se considera de inicio tardío cuando comienza después de los 60 años y tiene características distintivas propias. Objetivo: analizar las características demográficas, clínicas y del tratamiento de la artritis reumatoide de inicio tardío. Métodos: revisión documental automatizada en las bases de datos PubMed/Medline y Scielo (se utilizó Google Académico como motor de búsqueda) en el período comprendido entre enero y junio de 2023. Fueron seleccionados 24 artículos, el 75% actualizado. Resultados: existe una relación 1:1 entre sexos, con tres formas fundamentales de presentación de la enfermedad. Las características clínicas son heterogéneas, con mayor afectación de grandes articulaciones, más síntomas constitucionales, rigidez y manifestaciones extraarticulares mayormente de tipo cardiorrespiratorias, además de menor seropositividad. El pronóstico depende principalmente de la edad, de las comorbilidades, de la seropositividad y del tipo de tratamiento; que es peor que en pacientes más jóvenes. El manejo terapéutico tiene los mismos objetivos que en la enfermedad de inicio temprano y existe una tendencia a tratamientos menos intensivos con fármacos antirreumáticos. Conclusiones: la artritis reumatoide de inicio tardío posee características particulares que deben ser tomadas en cuenta para el diagnóstico certero y precoz, el adecuado manejo terapéutico y el control de los posibles efectos adversos y la buena adhesión al tratamiento.

Abstract Arthralgex is a proprietary polyherbal preparation used in clinics to treat rheumatoid arthritis for decades. Its safety evaluation has not been reported. The study is aimed at evaluating the safety of arthralgex using Wistar rats, as per OECD guidelines. According to OECD 407, rats of either gender were separated into six groups (n= 6 each). The dose of arthralgex was decided based on an acute toxicity study. Under the treatment group, separate set of rats received arthralgex in three dose levels like - low, medium, and high (200, 400 & 800 mg/kg/day; p.o for 28 days). Satellite groups received high dose (800 mg/kg/day, p.o for 28 days), and control group received equal volume of vehicle. On day 28, blood samples were collected to estimate hematology and biochemistry parameters. Subsequently, rats were euthanized to collect organs for weighing and histopathology. Satellite groups were maintained for an additional 14 days post-treatment to assess toxicity reversibility and euthanized on day 43. Arthralgex did not show any signs of toxicity or major change in body weight in the acute toxicity study. Arthralgex has no significant adverse effect on general health status as confirmed by body weight, feed intake, hematology, biochemistry, urine analysis, internal organs, relative organ weight, and histopathological evaluation after 28 day treatment. Arthralgex could be considered safe for short-term treatment. Present findings may help researchers in dose fixing for sub-chronic and chronic toxicity studies, which is essential for safety evaluation for long-term use. decades reported guidelines 407 n= n (n each. each . each) low medium 200, 200 (200 40 80 mg/kg/day mgkgday mg kg po p o 2 days. days) (80 days, , vehicle parameters Subsequently histopathology 1 posttreatment post 43 intake analysis shortterm short term subchronic sub studies longterm long use 20 (20 4 8 (8 (2 (

Resumo Arthralgex é uma preparação poli-herbal patenteada usada em clínicas para tratar a artrite reumatoide há décadas. Sua avaliação de segurança não foi relatada. O estudo tem como objetivo avaliar a segurança do arthralgex em ratos Wistar, conforme diretrizes da OCDE. De acordo com a OCDE, 407 ratos de ambos os sexos foram separados em seis grupos (n = 6 cada). A dose de arthralgex foi definida com base num estudo de toxicidade aguda. No grupo de tratamento, um conjunto separado de ratos recebeu arthralgex em três níveis de dose: baixo, médio e alto (200, 400 e 800 mg/kg/dia, respectivamente, por via oral, por 28 dias). Os grupos satélites receberam altas doses (800 mg/kg/dia, por via oral, por 28 dias), e o grupo controle recebeu igual volume. No dia 28, foram coletadas amostras de sangue para estimar parâmetros hematológicos e bioquímicos. Posteriormente, os ratos foram eutanasiados para coletar órgãos para pesagem e histopatologia. Os grupos satélites foram mantidos por mais 14 dias após o tratamento para avaliar a reversibilidade da toxicidade e sacrificados no dia 43. Arthralgex não mostrou quaisquer sinais de toxicidade ou alteração importante no peso corporal no estudo de toxicidade aguda. Arthralgex não tem efeito adverso significativo no estado geral de saúde, conforme confirmado pelo peso corporal, ingestão de ração, hematologia, bioquímica, análise de urina, órgãos internos, peso relativo dos órgãos e avaliação histopatológica após 28 dias de tratamento. Arthralgex pode ser considerado seguro para tratamento de curto prazo. As descobertas atuais podem ajudar os pesquisadores na fixação de doses para estudos de toxicidade subcrônica e crônica, o que é essencial para avaliação de segurança para uso a longo prazo. poliherbal poli herbal décadas relatada Wistar OCDE 40 n cada. cada . cada) aguda baixo 200, 200 (200 80 mgkgdia mg kg mg/kg/dia respectivamente oral 2 dias. dias) (80 dias, , volume bioquímicos Posteriormente histopatologia 1 43 saúde ração hematologia bioquímica urina internos prazo crônica 4 20 (20 8 (8 (2 (

Resumo Várias razões podem estar subjacentes ao aumento dramático da diabetes mellitus tipo 2. Um desses motivos é a base genética e variações. Os polimorfismos do receptor da vitamina D estão associados a diferentes doenças, como artrite reumatoide e diabetes. O objetivo deste estudo é investigar a possível associação de duas mutações identificadas ApaI (rs7975232) e TaqI (rs731236). Oitenta e nove indivíduos saudáveis e 56 pacientes com diabetes tipo 2 (T2D) foram investigados usando a técnica RFLP para genotipagem e haplotipagem também. A distribuição dos genótipos Apal não foi estatisticamente significativa entre o controle (P = 0,65), bem como para os pacientes diabéticos (P = 0,58). Para as frequências do alelo Taql, o alelo T foi de 0,61, onde o alelo G foi de 0,39. A distribuição de frequência dos genótipos Taql não foi estatisticamente significativa entre o controle (P = 0,26), bem como os pacientes diabéticos (P = 0,17). O risco relativo do alelo T do gene Apa1 é 1,28 e a razão de chances do mesmo alelo é 1,53, enquanto ambas as estimativas foram < 1,0 do alelo G. Da mesma forma, com o gene Taq1, os valores de risco relativo e razão de chances para o alelo T são 1,09 e 1,27, respectivamente, e ambas as estimativas do alelo C foram de 0,86 para o risco relativo e 0,79 para o odds ratio. O desequilíbrio de ligação par a par entre os dois SNPs Taq1 / apa1 foi estatisticamente significativo no grupo de controle (D = 0,218, D' = 0,925 e valor P < 0,001) e dados semelhantes em grupos diabéticos (D = 0,2, D' = 0,875 e valor P < 0,001). Esses dados sugerem que o alelo T de ambos os genes Apa1 e Taq1 está associado ao aumento do risco de diabetes tipo 2. Achamos que precisamos de um número maior de voluntários para chegar a uma conclusão mais precisa.

Abstract Several reasons may underlie the dramatic increase in type2 diabetes mellitus. One of these reasons is the genetic basis and variations. Vitamin D receptor polymorphisms are associated with different diseases such as rheumatoid arthritis and diabetes. The aim of this study is to investigate the possible association of two identified mutations ApaI (rs7975232) and TaqI (rs731236). Eighty-nine healthy individuals and Fifty-six Type 2 Diabetic (T2D) patients were investigated using RFLP technique for genotyping and haplotyping as well. The distribution of Apal genotypes was not statistically significant among the control (P=0.65) as well as for diabetic patients (P=0.58). For Taql allele frequencies of T allele was 0.61 where of G allele was 0.39. The frequency distribution of Taql genotypes was not statistically significant among the control (P=0.26) as well as diabetic patients (P=0.17). Relative risk of the allele T of Apa1 gene is 1.28 and the odds ratio of the same allele is 1.53, while both estimates were < 1.0 of the allele G. Similarly, with the Taq1 gene the relative risk and the odds ratio values for the allele T are 1.09 and 1.27 respectively and both estimates of the allele C were 0.86 for the relative risk and 0.79 for the odds ratio. The pairwise linkage disequilibrium between the two SNPs Taq1/apa1 was statistically significant in control group (D = 0.218, D' = 0.925 and P value < 0.001) and similar data in diabetic groups (D = 0.2, D' = 0.875 and P value < 0.001). These data suggest that the T allele of both genes Apa1 and Taq1 is associated with the increased risk of type 2 diabetes. We think that we need a larger number of volunteers to reach a more accurate conclusion.

ABSTRACT Background: Chikungunya fever is an emerging global infection transmitted by Aedes mosquitoes that manifests as an acute febrile illness with joint pain and can lead to chronic arthritis. The mechanism underlying chronic joint damage remains unclear; however, chronic chikungunya arthritis shares similarities with rheumatoid arthritis. Disease-modifying antirheumatic drugs have revolutionized rheumatoid arthritis treatment by preventing joint damage. However, the role of these therapies in chronic chikungunya arthritis has not been determined. We conducted a systematic review to evaluate the burden of joint structural damage in chronic chikungunya arthritis to help to define the role of disease-modifying therapy in this disease. Methods: This systematic review included retrospective and prospective studies, trials, and case reports evaluating joint damage caused by chikungunya virus. Various databases were searched without any date or language restrictions. Study selection was conducted independently by two researchers, and data were extracted from the articles selected. Results: A total of 108 studies were initially evaluated, with 8 meeting the inclusion criteria. Longitudinal studies have reported persistent joint pain from chikungunya infection and the progression of radiographic joint damage up to 13 years post-infection. Joint imaging revealed synovial inflammation, bone erosion, and cartilage destruction in patients with chronic chikungunya arthritis. Conclusions: Few studies have addressed chikungunya-induced joint damage, limiting our understanding of chronic chikungunya arthritis. Nevertheless, chronic chikungunya arthritis has similarities to rheumatoid arthritis. The success of early disease-modifying antirheumatic drug therapy in rheumatoid arthritis underscores the need for comprehensive research on its role in chikungunya arthritis. Background unclear however Diseasemodifying Disease modifying However determined diseasemodifying disease Methods trials virus restrictions researchers selected Results 10 evaluated criteria 1 postinfection. postinfection post infection. post-infection inflammation erosion Conclusions chikungunyainduced induced Nevertheless

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease that may cause joint deformities and seriously affect the normal life of the patients. In order to enable patients to receive timely attention and treatment, this study developed new diagnostic markers by exploring the expression and molecular mechanism of the long non-coding RNA NORAD (NORAD) in RA. Methods Participants including 77 RA patients and 52 healthy persons were enrolled, and the corresponding clinical data and serum samples were obtained. The NORAD and miR-204-5p expression were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The content of inflammatory cytokines (IL-6, TNF-α) were determined through enzyme-linked immunosorbent assay (ELISA). Luciferase activity reporter assay demonstrated the association between NORAD and miR-204-5p. In addition, receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of NORAD, and Pearson's correlation analysis was applied for the correlation analysis. Results NORAD was enriched in RA serum with high diagnostic value. Simultaneously, IL-6 and TNF-α levels were also upregulated (P < 0.001). The C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and anti-cyclic citrullinated peptide antibody (Anti-CCP) levels in RA patients were generally elevated (P < 0.001). NORAD was positively correlated with the levels of clinical indicators and inflammatory factors (P < 0.0001). Mechanistically, NORAD may affect the progression of RA by targeting and negatively regulating miR-204-5p. Conclusions There is a correlation between NORAD and the processes of RA, and NORAD has the potential to predict and diagnose the occurrence of RA. (RA treatment noncoding non coding (NORAD 7 5 enrolled obtained miR2045p miRp miR 204 5p p realtime real time RTqPCR. RTqPCR RT qPCR . (RT-qPCR) IL6, IL6 IL 6, 6 (IL-6 TNFα TNF α enzymelinked enzyme linked ELISA. ELISA (ELISA) miR2045p. 5p. addition ROC (ROC Pearsons Pearson s value Simultaneously IL- P 0.001. 0001 0.001 0 001 0.001) Creactive C reactive CRP, CRP , (CRP) RF, RF (RF) ESR (ESR anticyclic anti cyclic AntiCCP Anti CCP (Anti-CCP 0.0001. 00001 0.0001 0.0001) Mechanistically 20 (RT-qPCR (IL- (ELISA 000 0.00 00 (CRP (RF 0000 0.000 2 (IL 0.0 0.

Abstract Background The HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive. Methods Abatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified. The primary outcome was mean change in CDAI score over six months. Analyses were conducted in propensity score (PS)-trimmed and -matched populations overall and a biologic-experienced subgroup. Mixed-effects models were used. Results In the overall PS-trimmed (abatacept, n = 170; TNFi, n = 157) and PS-matched cohorts (abatacept, n = 111; TNFi, n = 111), there were numerically greater improvements in mean change in CDAI between abatacept and TNFi but were not statistically significant. Similar trends were seen for biologic-experienced patients, except that statistical significance was reached for mean change in CDAI in the PS-trimmed cohort (abatacept, 12.22 [95% confidence interval (95%CI) 10.13 to 14.31]; TNFi, 9.28 [95%CI 7.08 to 11.48]; p = 0.045). Conclusion In this real world cohort, there were numerical improvements in efficacy outcomes with abatacept over TNFi in patients with RA who were SE + and ACPA+, similar to results from a clinical trial population The only statistically significant finding after adjusting for covariates was greater improvement in CDAI with abatacept versus TNFi in the bio-experienced PS-trimmed cohort. . HLADRB1 HLADRB HLA DRB1 DRB HLA-DRB (SE (RA anticitrullinated anti ACPAs (ACPAs realworld (TNFi anticyclic cyclic antiCCP3 antiCCP CCP3 CCP (anti-CCP3 positive antiCCP3+ CCP3+ anti-CCP3 > ( 2 U/mL UmL U mL 10 identified months PStrimmed PS trimmed matched biologicexperienced biologic experienced subgroup Mixedeffects Mixed effects used abatacept, (abatacept 170 157 PSmatched 111 111, , 111) 1222 12 22 12.2 95% 95 [95 95%CI 95CI CI (95%CI 1013 13 10.1 14.31 1431 14 31 14.31] 928 9 28 9.2 708 7 08 7.0 11.48 1148 11 48 11.48] 0.045. 0045 0.045 0 045 0.045) ACPA ACPA+ bioexperienced bio (anti-CCP anti-CCP 1 17 15 122 12. [9 101 10. 14.3 143 3 92 9. 70 7. 11.4 114 4 004 0.04 04 [ 14. 11. 00 0.0 0.