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.

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: 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.

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 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.

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 (

ABSTRACT Connective tissue disease-associated interstitial lung disease (CTD-ILD) represents a group of systemic autoimmune disorders characterized by immune-mediated organ dysfunction. Systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myositis, and Sjögren’s syndrome are the most common CTDs that present with pulmonary involvement, as well as with interstitial pneumonia with autoimmune features. The frequency of CTD-ILD varies according to the type of CTD, but the overall incidence is 15%, causing an important impact on morbidity and mortality. The decision of which CTD patient should be investigated for ILD is unclear for many CTDs. Besides that, the clinical spectrum can range from asymptomatic findings on imaging to respiratory failure and death. A significant proportion of patients will present with a more severe and progressive disease, and, for those, immunosuppression with corticosteroids and cytotoxic medications are the mainstay of pharmacological treatment. In this review, we summarized the approach to diagnosis and treatment of CTD-ILD, highlighting recent advances in therapeutics for the various forms of CTD. diseaseassociated associated CTDILD (CTD-ILD immunemediated immune mediated dysfunction sclerosis arthritis myositis Sjögrens Sjögren s involvement features 15 15% mortality death those review CTDILD, ILD, 1

RESUMO Doença pulmonar intersticial associada à doença do tecido conjuntivo (DPI-DTC) representa um grupo de distúrbios autoimunes sistêmicos caracterizados por disfunção de órgãos imunomediada. Esclerose sistêmica, artrite reumatoide, miosite inflamatória idiopática e síndrome de Sjögren são as DTC mais comuns que apresentam acometimento pulmonar, bem como pneumonia intersticial com achados autoimunes. A frequência de DPI-DTC varia de acordo com o tipo de DTC, mas a incidência total é de 15%, causando um impacto importante na morbidade e mortalidade. A decisão sobre qual paciente com DTC deve ser investigado para DPI não é clara para muitas DTC. Além disso, o espectro clínico pode variar desde achados assintomáticos em exames de imagem até insuficiência respiratória e morte. Parte significativa dos pacientes apresentará doença mais grave e progressiva, e, para esses pacientes, imunossupressão com corticosteroides e medicamentos citotóxicos são a base do tratamento farmacológico. Nesta revisão, resumimos a abordagem do diagnóstico e tratamento de DPI-DTC, destacando os recentes avanços na terapêutica para as diversas formas de DTC. DPIDTC (DPI-DTC imunomediada sistêmica reumatoide 15 15% mortalidade disso morte progressiva farmacológico revisão DPIDTC, 1

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 Small joints are the primary target for rheumatoid arthritis (RA). However, few studies have investigated the quantitative aspects of these changes using a design-unbiased stereological method. Eight male Lewis rats were randomized to either an arthritis group (complete Freund’s adjuvant at the base of the tail) or a control group (saline solution). After 28 days the 5th metatarsophalangeal joints (5MTP joint) were decalcified and embedded in methylmethacrylate. The fingers were systematically sectioned perpendicular to the joint cartilage surface to produce 10-12 vertical sections. We quantified the morphological changes in four steps: (i) determination of the Cavalieri volume of joints, (ii) ascertainment of the volume density of tissues, (iii) estimation of the cartilage surface area, and (iv) 3-D counting of chondrocytes and mast cells. Arthritic joints were edematous due to a significant increase in the periarticular region. Synovium volume was inversely related to synovial space. Stereological analysis provided details of changes induced by chronic inflammation, particularly edema, synovial space narrowing, synovitis, mast cell recruitment, bone remodeling, and chondrocyte loss in 5MTP joints. These interrelated pathological changes in chronic inflammation collectively contribute to the progressive joint damage and dysfunction seen in arthritis. RA. RA . (RA) However designunbiased design unbiased method complete Freunds Freund s tail saline solution. solution solution) 2 th MTP methylmethacrylate 1012 10 12 10-1 sections steps i (i ii (ii tissues iii (iii area iv (iv 3D D 3 cells region edema narrowing synovitis recruitment remodeling (RA 101 1 10-

ABSTRACT BACKGROUND AND OBJECTIVES: Buprenorphine is a partial agonist semi-synthetic opioid used as an option in the treatment of patients with moderate to severe pain. The only presentation of buprenorphine available in Brazil is for transdermal use. This is an important route of drug administration, especially for the treatment of chronic pain, as it has several advantages, however it is not free from complications. The objective of this study was to present a serious adverse skin reaction after the use of transdermal buprenorphine, requiring surgical intervention. CASE REPORT: Female patient, 63 years old, hypertensive and diabetic, diagnosed with rheumatoid arthritis, fibromyalgia syndrome and lumbar disc herniation, with severe chronic pain, advised to use transdermal buprenorphine 10 mg to help control algic. After 24 hours of use, the patient developed erythema and local itching, requiring removal of the adhesive, but the lesion progressively worsened with the formation of an abscess and the need for surgical drainage. CONCLUSION: Transdermal buprenorphine has a favorable safety and tolerability profile, as it reduces the risk of unwanted effects such as respiratory depression, constipation and suicidal ideation. However, its use in senior patients with comorbidities, such as the immunosuppression described in this case, requires greater vigilance, due to the possibility of developing more serious adverse reactions. OBJECTIVES semisynthetic semi synthetic pain administration advantages complications intervention REPORT 6 old diabetic arthritis herniation 1 algic 2 itching adhesive drainage CONCLUSION profile depression ideation However comorbidities case vigilance reactions

RESUMO JUSTIFICATIVA E OBJETIVOS: A buprenorfina é um opioide agonista parcial semissintético utilizado como opção no tratamento de pacientes com dor de moderada a intensa. A única apresentação disponível da buprenorfina no Brasil é para uso por via transdérmica. Esta é uma via importante de administração de fármacos, principalmente para o tratamento de dor crônica, já que apresenta diversas vantagens, no entanto não é isenta de complicações. O objetivo deste estudo foi apresentar uma reação cutânea adversa grave após o uso de buprenorfina transdérmica, com necessidade de intervenção cirúrgica. RELATO DO CASO: Paciente do sexo feminino, 63 anos, hipertensa e diabética, com diagnósticos de artrite reumatoide, síndrome fibromiálgica e hérnia de disco lombar, portadora de dor crônica intensa, com orientação de utilizar buprenorfina transdérmica 10 mg para auxiliar o controle álgico. Após 24 h de uso, a paciente evoluiu com eritema e prurido local, sendo indicada a remoção do adesivo, porém a lesão piorou progressivamente com formação de abscesso e necessidade de drenagem cirúrgica. CONCLUSÃO: A buprenorfina transdérmica apresenta um perfil favorável de segurança e tolerabilidade, pois reduz o risco de efeitos indesejados, como depressão respiratória, constipação e ideação suicida. No entanto, seu uso em pacientes idosos portadores de comorbidades, como a imunossupressão descrita no caso, exige maior vigilância, devido à possibilidade de desenvolvimento de reações adversas mais graves. OBJETIVOS intensa fármacos vantagens complicações cirúrgica CASO feminino 6 anos diabética reumatoide lombar 1 álgico 2 local adesivo CONCLUSÃO tolerabilidade indesejados respiratória suicida comorbidades caso vigilância graves

Abstract Humans are exposed to natural compounds such as phytoestrogens primarily through diet and supplements. These compounds promote health by alleviating the symptoms and illnesses associated with menopause and arthritis. Diosgenin (DSG) occurs naturally in plants such as Dioscorea villosa (DV) and binds to estrogen receptors, so it may have similar effects to this hormone, including against arthritis. Thus, we investigated the effect of chronic treatment with dry extract of DV and its phytoestrogen DSG on ovariectomized mice with arthritis. We found that dry extract of Dioscorea villosa (DV) contains the phytoestrogen diosgenin (DSG) in its composition. Furthermore, arthritic mice treated with DV and DSG showed reduced neutrophil accumulation in the articular cartilage. Also, the dry extract of DV administered orally (v.o) did not alter the leukocyte count in the joints or promote changes in the reproductive tract. However, DSG altered these parameters, with possible beneficial effects by reducing symptoms related to reproductive aging. Thus, oral treatment with dry extract of DV and subcutaneous (s.c) treatment with DSG showed promise by acting against inflammation caused by arthritis and reducing symptoms in the reproductive tract due to menopause. supplements (DSG (DV receptors hormone Thus composition Furthermore cartilage Also v.o vo v o (v.o However parameters aging s.c sc s c (s.c

Abstract Background Interstitial lung disease (ILD) remains one of the most important causes of morbidity and mortality in patients with Connective Tissue Diseases (CTD). This study evaluated the impact of hospitalization on mortality in an ethnically and racially diverse cohort of CTD-ILD patients. Methods We conducted a medical records review study at Montefiore Medical Center, Bronx, NY. We included 96 patients and collected data on demographic characteristics, reasons for hospitalization, length of stay, immunosuppressant therapy use, and mortality. We stratified our patients into two cohorts: hospitalized and nonhospitalized. The hospitalized cohort was further subdivided into cardiopulmonary and non-cardiopulmonary admissions. Two-sample tests or Wilcoxon's rank sum tests for continuous variables and Chi-square or Fisher's exact tests for categorical variables were used for analyses as deemed appropriate. Results We identified 213 patients with CTD-ILD. Out of them, 96 patients met the study's inclusion criteria. The majority of patients were females (79%), and self-identified as Hispanic (54%) and Black (40%). The most common CTDs were rheumatoid arthritis (RA) (29%), inflammatory myositis (22%), and systemic sclerosis (15%). The majority (76%) of patients required at least one hospitalization. In the non-hospitalized group, no deaths were observed, however we noted significant increase of mortality risk in hospitalized group (p = 0.02). We also observed that prolonged hospital stay (> 7 days) as well as older age and male sex were associated with increased mortality. Conclusion Prolonged (> 7 days) hospital stay and hospitalization for cardiopulmonary causes, as well as older age and male sex were associated with an increased mortality risk in our cohort of CTD-ILD patients. ILD (ILD CTD. CTD . (CTD) CTDILD Center Bronx NY 9 characteristics use cohorts nonhospitalized noncardiopulmonary non admissions Twosample Two sample Wilcoxons Wilcoxon s Chisquare Chi square Fishers Fisher appropriate 21 CTDILD. ILD. them studys criteria 79%, 79 79% , (79%) selfidentified self 54% 54 (54% 40%. 40 40% (40%) RA (RA 29%, 29 29% (29%) 22%, 22 22% (22%) 15%. 15 15% (15%) 76% 76 (76% p 0.02. 002 0.02 0 02 0.02) > ( days (CTD 2 (79% 5 (54 4 (40% (29% (22% 1 (15% (76 00 0.0 (79 (5 (40 (29 (22 (15 (7 0. (4 (2 (1

Abstract Background Knowledge of patients about Rheumatoid Arthritis (RA) is a necessary aspect to better approach self-management support in a patient-centered manner. The research instrument known as the Rheumatoid Arthritis Knowledge Assessment Scale (RAKAS), consisting of 13 items, is simple, reliable and reproducible, and can be applied in both clinical practice and research protocols. Objectives This study aimed to translate and culturally adapt the RAKAS vocabulary into Brazilian Portuguese and to evaluate its concurrent validity. Methods The RAKAS was translated into Brazilian Portuguese and administered to 52 elderly women with RA recruited between May 2021 and May 2022. Concurrent validity was assessed using the Spearman's correlation coefficient between RAKAS and Patient Knowledge Questionnaire (PKQ). Results The participants considered RAKAS-13/BRAZIL easy to understand and did not report any doubts in answering the final version. Concurrent validity of the RAKAS–13/BRAZIL was low compared to the PKQ (ρ = 0.283, p = 0.038). Conclusion The Brazilian Portuguese version of the RAKAS (RAKAS–13/BRASIL) proved to be a questionnaire that was easy and quick to administer to assess patient knowledge about Rheumatoid Arthritis, despite its low correlation with the PKQ in the present study. (RA selfmanagement self management patientcentered centered manner RAKAS, , (RAKAS) 1 items simple reproducible protocols 5 202 2022 Spearmans Spearman s PKQ. . (PKQ) RAKAS13/BRAZIL RAKAS13BRAZIL RAKASBRAZIL 13/BRAZIL BRAZIL ρ 0283 0 283 0.283 0.038. 0038 0.038 038 0.038) RAKAS–13/BRASIL RAKAS13BRASIL RAKASBRASIL BRASIL (RAKAS–13/BRASIL (RAKAS 20 (PKQ RAKAS13 13BRAZIL 028 28 0.28 003 0.03 03 2 RAKAS1 02 0.2 00 0.0 0.

As an oral Janus kinase 1 inhibitor, upadacitinib shows good activity in the treatment of rheumatoid arthritis, especially for other drug-resistant and refractory rheumatoid arthritis patients. A key step in the synthesis of upadacitinib is the introduction of ethyl on the pyrroline ring. Here, a FeCl3/p-aminophenol catalyst system was used to increase the ethyl introduction for synthesis of pyrroline building blocks of upadaticinib. This catalytic system allows milder reaction conditions and increases the yield of this step by 25% compared to the existing reports, and the scale-up experiment is still effective. In addition, a possible FeII/FeIV catalytic mechanism for this reaction was also proposed. inhibitor drugresistant drug resistant patients ring Here FeCl3/paminophenol FeCl3paminophenol FeClpaminophenol FeCl3/p aminophenol FeCl3 p FeCl upadaticinib 25 reports scaleup scale up effective addition FeIIFeIV FeII FeIV proposed paminophenol FeCl3p FeClp 2

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