Significance of clinical-immunological patterns and diagnostic yield of biopsies in microscopic polyangiitis and granulomatosis with polyangiitis.

BACKGROUND: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. RESULTS: This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. CONCLUSIONS: The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.

Decoding CD4+ T cell transcriptome in giant cell arteritis: Novel pathways and altered cross-talk with monocytes.

BACKGROUND: Giant cell arteritis (GCA) is an immune-mediated large-vessels vasculitis with complex etiology. Although the pathogenic mechanisms remain poorly understood, a central role for CD4+ T cells has been demonstrated. In this context, understanding the transcriptome dysregulation in GCA CD4+ T cells will yield new insights into its pathogenesis. METHODS: Transcriptome analysis was conducted on CD4+ T cells from 70 patients with GCA with different disease activity and treatment status (active patients before treatment and patients in remission with and without glucocorticoid treatment), and 28 healthy controls. The study also evaluated potential impacts of DNA methylation on gene expression alterations and assessed cross-talk with CD14+ monocytes. RESULTS: This study has uncovered a substantial number of genes and pathways potentially contributing to the pathogenicity of CD4+ T cells in GCA. Specifically, CD4+ T cells from GCA patients with active disease exhibited altered expression levels of genes involved in multiple immune-related processes, including various interleukins (IL) signaling pathways. Notably, IL-2, a decisive interleukin for regulatory T cells homeostasis, was among the most significant. Additionally, impaired apoptotic pathways appear crucial in GCA development. Our findings also suggest that histone-related epigenetic pathways may be implicated in promoting an inflammatory phenotype in GCA active patients. Finally, our study observed altered signaling communication, such as the Jagged-Notch signaling, between CD4+ T cells and monocytes that could have pathogenic relevance in GCA. CONCLUSIONS: Our study suggests the participation of novel cytokines and pathways and the occurrence of a disruption of monocyte-T cell crosstalk driving GCA pathogenesis.

Factors associated with early hydroxychloroquine-induced retinal toxicity in patients with systemic lupus erythematosus.

PURPOSE: Hydroxychloroquine is currently recommended for the treatment of systemic lupus erythematosus (SLE), but it can cause irreversible retinal toxicity. This study aimed to identify factors associated with early hydroxychloroquine-induced retinal toxicity in patients with SLE from a single centre for 20 years. METHODS: SLE patients diagnosed between 1998 and 2017 and followed up for at least 1 year were included. Demographic, clinical, laboratory and therapeutic data were collected from the electronic medical records and retrospectively analysed. Early hydroxychloroquine-induced retinal toxicity was defined as the development of macular toxicity within the first 5 years of hydroxychloroquine treatment. RESULTS: A total of 345 patients followed for a median of 15 years were analysed; 337 (97.7%) patients received hydroxychloroquine, 38 (11.3%) of them presented with retinal toxicity, and 10 (3%) developed early retinal toxicity. These patients had a mean treatment duration of 3.3 years with a mean cumulative dose of 241 g. Patients were diagnosed by visual field (VF) and fundoscopy, and two were also assessed using spectral domain optical coherence tomography (SD-OCT). The median (IQR) age of patients with early toxicity was 56 (51-66) years, and 80% were female. Factors independently associated with early hydroxychloroquine-induced retinal toxicity were lupus anticoagulant positivity (OR 4.2; 95% CI 1.2-15.5) and hypercholesterolaemia (OR 5.6; 95% CI 1.5-21.5). CONCLUSION: Our results suggest that lupus anticoagulant positivity and hypercholesterolaemia among SLE patients may be risk factors for early hydroxychloroquine-induced retinal toxicity, regardless of the dose or duration of treatment.

Maternal and fetal outcomes of pregnancy in women with primary systemic vasculitis: A single-center cohort study of 20 patients and 30 pregnancies.

OBJECTIVES: To analyze pregnancy outcomes of patients with primary systemic vasculitis followed in a third-level referral center. METHODS: Retrospective cohort study of all pregnant women with systemic vasculitis followed between 2009 and 2022 at the High-Risk Pregnancy Clinic of the Department of Systemic Autoimmune Diseases of the Hospital Clínic, Barcelona. RESULTS: Twenty women with primary vasculitis were identified, with a total of 30 pregnancies. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (n = 7) and Behçet disease (n = 4) were the most frequent types of vasculitis. All women had the diagnosis of vasculitis before pregnancy, with a median time between disease diagnosis and pregnancy of 5.8 years (range: 2 months-29 years). Most were in remission at conception (76.7 %). During pregnancy, a vasculitis flare occurred in 4 (13.3 %) patients (one each with Takayasu arteritis, eosinophilic granulomatosis with polyangiitis [EGPA], IgA vasculitis [IgAV], and Behçet disease [BD]). Four (16.7 %) of the successful pregnancies had post-partum relapses (one each with EGPA, granulomatosis with polyangiitis, IgAV, and BD). Eighty percent of pregnancies resulted in live babies. In four cases (13.3 %), medical termination of pregnancy was decided, considering the mother or baby health risk. There were two spontaneous miscarriages, and no stillbirths or neonatal deaths. Preeclampsia was the most frequent maternal complication (25 %). Newborns were preterm in 24 % and low birthweight in 20 % of cases. No maternal deaths occurred. CONCLUSIONS: This cohort study shows that vasculitis relapses during pregnancy and post-partum, together with other pregnancy complications, occur in a considerable number of patients with systemic vasculitides, although a final good pregnancy outcome can be expected in most cases. These findings emphasize the convenience of managing these special situations in expert reference centers.

New proposal for a multimodal imaging approach for the subclinical detection of hydroxychloroquine-induced retinal toxicity in patients with systemic lupus erythematosus.

OBJECTIVE: To compare multimodal structural and functional diagnostic methods in patients with systemic lupus erythematosus (SLE) treated with hydroxychloroquine, to identify the best complementary approach for detecting subclinical retinal toxicity. METHODS: A cross-sectional, unicentric study was conducted on patients with SLE treated with hydroxychloroquine. Each patient underwent a comprehensive ophthalmic evaluation, comprising structural tests (spectral-domain optical coherence tomography (SD-OCT), en face OCT, en face OCT angiography (OCTA), fundus autofluorescence (FAF)) and functional tests (automated perimetry for visual field (VF) testing, multifocal electroretinography (mfERG)). A diagnosis of macular toxicity required the presence of abnormalities in at least one structural and functional test. The Kappa Concordance Index was used to assess the concordance among the different tests in detecting potential macular toxicity-associated alterations. RESULTS: Sixty-six patients with SLE (132 eyes) were consecutively enrolled. Four (6.1%) patients developed subclinical hydroxychloroquine-induced retinal toxicity without visual acuity impairment. The proportion of abnormal results was 24% for both en face OCT and en face OCTA. Regarding functional analysis, VF was less specific than mfERG in detecting subclinical retinal toxicity (VF specificity 47.5%). En face OCT and en face OCTA structural findings showed better concordance, with a kappa index >0.8, and both identified the same cases of toxicity as FAF. CONCLUSION: Although structural OCT and VF are frequently used to screen for hydroxychloroquine-induced retinal toxicity, our findings suggest that a combination of mfERG, en face OCT and en face OCTA could improve the diagnostic accuracy for subclinical retinal damage. This study emphasises the importance of a multimodal imaging strategy to promptly detect signs of hydroxychloroquine-induced retinal toxicity.

Update on ocular manifestations of the main monogenic and polygenic autoinflammatory diseases.

Autoinflammatory diseases include disorders with a genetic cause and also complex syndromes associated to polygenic or multifactorial factors. Eye involvement is present in many of them, with different extent and severity. The present review covers ophthalmological lesions in the most prevalent monogenic autoinflammatory diseases, including FMF (familial Mediterranean fever), TRAPS (TNF receptor-associated periodic syndrome), CAPS (cryopyrin-associated periodic syndromes), Blau syndrome, DADA2 (deficiency of adenosine deaminase 2), DITRA (deficiency of the interleukin-36 receptor antagonist), other monogenic disorders, including several ubiquitinopathies, interferonopathies, and the recently described ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome, and VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Among polygenic autoinflammatory diseases, ocular manifestations have been reviewed in Behçet's disease, PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) syndrome, Still's disease and autoinflammatory bone diseases, which encompass CRMO (chronic recurrent multifocal osteomyelitis) and SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome.

Disease phenotypes in adult patients with suspected undifferentiated autoinflammatory diseases and PFAPA syndrome: Clinical and therapeutic implications.

BACKGROUND: Undifferentiated autoinflammatory diseases are characterized by recurrent or persistent fever, usually combined with other inflammatory manifestations, and negative or inconclusive genetic studies for monogenic autoinflammatory disorders. AIMS: To define and characterize disease phenotypes in adult patients diagnosed in an adult reference center with undifferentiated autoinflammatory diseases, and to analyze the efficacy of the drugs used in order to provide practical diagnostic and therapeutic recommendations. METHODS: Retrospective study (2015-2022) of patients with undifferentiated autoinflammatory diseases among all patients visited in our reference center. Demographic, clinical, laboratory features and detailed therapeutic information was collected. RESULTS: Of the 334 patients with a suspected autoinflammatory disease, 134 (40%) patients (61% women) were initially diagnosed with undifferentiated autoinflammatory diseases. Mean age at disease onset and at diagnosis was 28.7 and 37.7 years, respectively. In 90 (67.2%) patients, symptoms started during adulthood. Forty-four (32.8%) patients met diagnostic/classification criteria for adult PFAPA syndrome. In the remaining patients, four additional phenotypes were differentiated according to the predominant manifestations: a) Predominantly fever phenotype (n = 18; 13.4%); b) Predominantly abdominal/pleuritic pain phenotype (n = 9; 6.7%); c) Predominantly pericarditis phenotype (n = 18; 13.4%), and d) Complex syndrome phenotype (n = 45; 33.6%). Prednisone (mainly on demand), colchicine and anakinra were the drugs commonly used. Overall, complete responses were achieved with prednisone in 41.3%, colchicine in 40.2%, and anakinra in 58.3% of patients in whom they were used. By phenotypes, prednisone on demand was more effective in adult PFAPA syndrome and colchicine in patients with the abdominal/pleuritic pain pattern and PFAPA syndrome. Patients with complex syndrome achieved complete responses with prednisone (21.9%), colchicine (25.7%) and anakinra (44.4%), and were the group more often requiring additional immunosuppressive drugs. CONCLUSIONS: The analysis of the largest single-center series of adult patients with undifferentiated autoinflammatory diseases identified and characterized different disease phenotypes and their therapeutic approaches. This study is expected to contribute to increase the awareness of physicians for an early identification of these conditions, and to provide the best known therapeutic options.

Ocular Manifestations in Juvenile Behçet's Disease: A Registry-Based Analysis from the AIDA Network.

INTRODUCTION: This study aims to characterize ocular manifestations of juvenile Behçet's disease (jBD). METHODS: This was a registry-based observational prospective study. All subjects with jBD from the Autoinflammatory Diseases Alliance (AIDA) Network BD Registry showing ocular manifestations before 18 years were enrolled. RESULTS: We included 27 of 1000 subjects enrolled in the registry (66.7% male patients, 45 affected eyes). The median (interquartile range [IQR]) age at ocular involvement was 14.2 (4.7) years. Uveitis affected 91.1% of eyes (anterior 11.1%, posterior 40.0%, panuveitis 40.0%), retinal vasculitis 37.8% and other manifestations 19.8%. Later onset (p = 0.01) and male predominance (p = 0.04) characterized posterior involvement. Ocular complications occurred in 51.1% of eyes. Patients with complications had earlier onset (p < 0.01), more relapses (p = 0.02) and more prolonged steroidal treatment (p = 0.02). The mean (standard deviation [SD]) central macular thickness (CMT) at the enrolment and last visit was 302.2 (58.4) and 293.3 (78.2) µm, respectively. Fluorescein angiography was pathological in 63.2% of procedures, with a mean (SD) Angiography Scoring for Uveitis Working Group (ASUWOG) of 17.9 (15.5). At the last visit, ocular damage according to the BD Overall Damage Index (BODI) was documented in 73.3% of eyes. The final mean (SD) best corrected visual acuity (BCVA) logMAR was 0.17 (0.47) and blindness (BCVA logMAR < 1.00 or central visual field ≤ 10°) occurred in 15.6% of eyes. At multivariate regression analysis, human leukocyte antigen (HLA)-B51 + independently predicted a + 0.35 change in the final BCVA logMAR (p = 0.01), while a higher BCVA logMAR at the first assessment (odds ratio [OR] 5.80; p = 0.02) independently predicted blindness. CONCLUSIONS: The results of this study may be leveraged to guide clinical practice and future research on this rare sight-threatening condition.

Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study.

BACKGROUND: Giant cell arteritis is an age-related vasculitis that mainly affects the aorta and its branches in individuals aged 50 years and older. Current options for diagnosis and treatment are scarce, highlighting the need to better understand its underlying pathogenesis. Genome-wide association studies (GWAS) have emerged as a powerful tool for unravelling the pathogenic mechanisms involved in complex diseases. We aimed to characterise the genetic basis of giant cell arteritis by performing the largest GWAS of this vasculitis to date and to assess the functional consequences and clinical implications of identified risk loci. METHODS: We collected and meta-analysed genomic data from patients with giant cell arteritis and healthy controls of European ancestry from ten cohorts across Europe and North America. Eligible patients required confirmation of giant cell arteritis diagnosis by positive temporal artery biopsy, positive temporal artery doppler ultrasonography, or imaging techniques confirming large-vessel vasculitis. We assessed the functional consequences of loci associated with giant cell arteritis using cell enrichment analysis, fine-mapping, and causal gene prioritisation. We also performed a drug repurposing analysis and developed a polygenic risk score to explore the clinical implications of our findings. FINDINGS: We included a total of 3498 patients with giant cell arteritis and 15 550 controls. We identified three novel loci associated with risk of giant cell arteritis. Two loci, MFGE8 (rs8029053; p=4·96 × 10-8; OR 1·19 [95% CI 1·12-1·26]) and VTN (rs704; p=2·75 × 10-9; OR 0·84 [0·79-0·89]), were related to angiogenesis pathways and the third locus, CCDC25 (rs11782624; p=1·28 × 10-8; OR 1·18 [1·12-1·25]), was related to neutrophil extracellular traps (NETs). We also found an association between this vasculitis and HLA region and PLG. Variants associated with giant cell arteritis seemed to fulfil a specific regulatory role in crucial immune cell types. Furthermore, we identified several drugs that could represent promising candidates for treatment of this disease. The polygenic risk score model was able to identify individuals at increased risk of developing giant cell arteritis (90th percentile OR 2·87 [95% CI 2·15-3·82]; p=1·73 × 10-13). INTERPRETATION: We have found several additional loci associated with giant cell arteritis, highlighting the crucial role of angiogenesis in disease susceptibility. Our study represents a step forward in the translation of genomic findings to clinical practice in giant cell arteritis, proposing new treatments and a method to measure genetic predisposition to this vasculitis. FUNDING: Institute of Health Carlos III, Spanish Ministry of Science and Innovation, UK Medical Research Council, and National Institute for Health and Care Research.

The Systemic Score May Identify Life-Threatening Evolution in Still Disease: Data from the GIRRCS AOSD-Study Group and the AIDA Network Still Disease Registry.

OBJECTIVE: We aimed to evaluate the clinical usefulness of the systemic score in the prediction of life-threatening evolution in Still disease. We also aimed to assess the clinical relevance of each component of the systemic score in predicting life-threatening evolution and to derive patient subsets accordingly. METHODS: A multicenter, observational, prospective study was designed including patients included in the Gruppo Italiano Di Ricerca in Reumatologia Clinica e Sperimentale Adult-Onset Still Disease Study Group and the Autoinflammatory Disease Alliance Network Still Disease Registry. Patients were assessed to see if the variables to derive the systemic score were available. The life-threatening evolution was defined as mortality, whatever the clinical course, and/or macrophage activation syndrome, a secondary hemophagocytic lymphohistiocytosis associated with a poor prognosis. RESULTS: A total of 597 patients with Still disease were assessed (mean ± SD age 36.6 ± 17.3 years; male 44.4%). The systemic score, assessed as a continuous variable, significantly predicted the life-threatening evolution (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.07-1.42; P = 0.004). A systemic score ≥7 also significantly predicted the likelihood of a patient experiencing life-threatening evolution (OR 3.36; 95% CI 1.81-6.25; P < 0.001). Assessing the clinical relevance of each component of the systemic score, liver involvement (OR 1.68; 95% CI 1.48-2.67; P = 0.031) and lung disease (OR 2.12; 95% CI 1.14-4.49; P = 0.042) both significantly predicted life-threatening evolution. The clinical characteristics of patients with liver involvement and lung disease were derived, highlighting their relevance in multiorgan disease manifestations. CONCLUSION: The clinical utility of the systemic score was shown in identifying Still disease at a higher risk of life-threatening evolution in a large cohort. Furthermore, the clinical relevance of liver involvement and lung disease was highlighted.

Risk for cancer development in familial Mediterranean fever and associated predisposing factors: an ambidirectional cohort study from the international AIDA Network registries.

Objective: Inflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF. Methods: The risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still's disease patients and Behçet's disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression. Results: 580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet's disease patients and 497 Still's disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still's disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet's disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (ß1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (ß1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (ß1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (ß1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (ß1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (ß1 = 2.089, 95% CI. 0.7-3.5, p=0.002). Conclusions: The risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

Orbital/ocular inflammatory involvement in VEXAS syndrome: Data from the international AIDA network VEXAS registry.

VEXAS syndrome is a recently described monogenic autoinflammatory disease capable of manifesting itself with a wide array of organs and tissues involvement. Orbital/ocular inflammatory manifestations are frequently described in VEXAS patients. The objective of this study is to further describe orbital/ocular conditions in VEXAS syndrome while investigating potential associations with other disease manifestations. In the present study, twenty-seven out of 59 (45.8 %) VEXAS patients showed an inflammatory orbital/ocular involvement during their clinical history. The most frequent orbital/ocular affections were represented by periorbital edema in 8 (13.6 %) cases, episcleritis in 5 (8.5 %) patients, scleritis in 5 (8.5 %) cases, uveitis in 4 (6.8 %) cases, conjunctivitis in 4 (6.8 %) cases, blepharitis in 3 (5.1 %) cases, orbital myositis in 2 (3.4 %) cases. A diagnosis of systemic immune-mediated disease was observed in 15 (55.6 %) cases, with relapsing polychondritis diagnosed in 12 patients. A significant association was observed between relapsing polychondritis and orbital/ocular involvement in VEXAS syndrome (Relative Risk: 2.37, 95 % C.I. 1.03-5.46, p = 0.048). Six deaths were observed in the whole cohort of patients after a median disease duration of 1.2 (IQR=5.35) years, 5 (83.3 %) of which showed orbital/ocular inflammatory involvement. In conclusion, this study confirms that orbital/ocular inflammatory involvement is a common finding in VEXAS patients, especially when relapsing polychondritis is diagnosed. This makes ophthalmologists a key figure in the diagnostic process of VEXAS syndrome. The high frequency of deaths observed in this study seems to suggest that patients with orbital/ocular involvement may require increased attention and more careful follow-up.

Effectiveness and Safety of Biosimilars in Pediatric Non-infectious Uveitis: Real-Life Data from the International AIDA Network Uveitis Registry.

INTRODUCTION: Since many biological drug patents have expired, biosimilar agents (BIOs) have been developed; however, there are still some reservations in their use, especially in childhood. The aim of the current study is to evaluate the efficacy and safety of tumor necrosis factor (TNF) inhibitors BIOs as treatment for pediatric non-infectious uveitis (NIU). METHODS: Data from pediatric patients with NIU treated with TNF inhibitors BIOs were drawn from the international AutoInflammatory Disease Alliance (AIDA) registries dedicated to uveitis and Behçet's disease. The effectiveness and safety of BIOs were assessed in terms of frequency of relapses, risk for developing ocular flares, best-corrected visual acuity (BCVA), glucocorticoids (GCs)-sparing effect, drug survival, frequency of ocular complications, and adverse drug event (AE). RESULTS: Forty-seven patients (77 affected eyes) were enrolled. The BIOs employed were adalimumab (ADA) (89.4%), etanercept (ETA) (5.3%), and infliximab (IFX) (5.3%). The number of relapses 12 months prior to BIOs and at last follow-up was 282.14 and 52.43 per 100 patients/year. The relative risk of developing ocular flares before BIOs introduction compared to the period following the start of BIOs was 4.49 (95% confidence interval [CI] 3.38-5.98, p = 0.004). The number needed to treat (NNT) for ocular flares was 3.53. Median BCVA was maintained during the whole BIOs treatment (p = 0.92). A significant GCs-sparing effect was observed throughout the treatment period (p = 0.002). The estimated drug retention rate (DRR) at 12-, 24-, and 36-month follow-up were 92.7, 83.3, and 70.8%, respectively. The risk rate for developing structural ocular complications was 89.9/100 patients/year before starting BIOs and 12.7/100 patients/year during BIOs treatment, with a risk ratio of new ocular complications without BIOs of 7.1 (CI 3.4-14.9, p = 0.0003). Three minor AEs were reported. CONCLUSIONS: TNF inhibitors BIOs are effective in reducing the number of ocular uveitis relapses, preserving visual acuity, allowing a significant GCs-sparing effect, and preventing structural ocular complications. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05200715.

Embolización de la arteria gástrica izquierda: un novedoso procedimiento para el tratamiento de la obesidad / Left gastric artery embolization: a novel procedure for the treatment of obesity

Introducción: La embolización de la arteria gástrica izquierda, es una técnica novedosa, mínimamente invasiva que se investiga como un método alternativo, a menudo complementario, para controlar el apetito y el peso corporal a través de la reducción de la secreción de la hormona grelina. Objetivo: Describir la seguridad y la eficacia de la embolización de la arteria gástrica izquierda, como procedimiento terapéutico para el tratamiento de la obesidad. Método: Se realizó una búsqueda de literatura relevante sobre el tema en el segundo semestre de 2019. Se utilizaron como buscadores de información científica a Pubmed y a Google Académico; se revisaron 54 artículos, de los cuales 36 fueron referenciados. Conclusiones: La seguridad y la eficacia de la embolización de la arteria gástrica izquierda como proceder terapéutico para el tratamiento de la obesidad fue aceptable en la mayoría de los estudios revisados; la escasez de la evidencia (pocos casos) y la falta de protocolos estandarizados para esta intervención, requieren de ensayos clínicos aleatorizados, con una muestra mayor de casos y a más largo plazo.

Introduction: left gastric artery embolization is a novel, minimally invasive technique that is being investigated as an alternative method, often complementary, to control appetite and body weight by means of reducing the secretion of the ghrelin hormone. Objective: to describe the safety and efficacy of left gastric artery embolization as a therapeutic procedure for the treatment of obesity. Methods: a review of the relevant literature on the subject was carried out in the second semester of 2019. Pubmed and Google Scholar were used as scientific information search engines; 54 articles were reviewed, of which 36 were referenced. Conclusions: the safety and efficacy of left gastric artery embolization as a therapeutic procedure for the treatment of obesity was acceptable in most of the reviewed studies; the lack of evidence (few cases) and standardized protocols for this intervention require randomized clinical trials, with a larger sample of cases and over a longer period of time.

Papel de la neuropatía diabética en la aparición y desarrollo del síndrome del pie diabético / Role of Diabetic Neuropathy in the Onset and Development of Diabetic Foot Syndrome

Introducción: La neuropatía diabética es la complicación más frecuente de la diabetes mellitus y una de sus posibles consecuencias es el síndrome del pie diabético. Los médicos del primer nivel de atención deben conocer el comportamiento clínico de la neuropatía diabética y, sobre todo, como influye en la aparición y desarrollo del síndrome del pie diabético. Objetivo: Describir el papel de la neuropatía diabética en la aparición y desarrollo del síndrome del pie diabético. Métodos: Para la obtención de la información se utilizaron como motores de búsqueda de información científica los correspondientes a Scielo, Pubmed, y Google Académico. Se usaron como palabras clave: diabetes mellitus; neuropatía diabética; pie diabético; síndrome de pie diabético; úlcera de pie diabético; ataque de pie diabético. Se evaluaron diferentes trabajos de revisión, investigación y páginas web, y se excluyeron los artículos que tuvieran más de 10 años de publicados, en idiomas diferentes al español, portugués e inglés y que no se refirieran al tema de estudio a través del título. Esto permitió la cita de 45 referencias bibliográficas. Conclusiones: La neuropatía diabética constituye el principal factor de riesgo en la aparición y desarrollo del síndrome del pie diabético, sobre todo cuando se asocia a artropatía (defectos podálicos), enfermedad vascular periférica y/o sepsis. El control de la glucemia, la detección temprana del pie de riesgo y el cuidado preventivo de los miembros inferiores, repercutirá favorablemente en la salud y bienestar del paciente(AU)

Introduction: Diabetic neuropathy is the most frequent complication of diabetes mellitus and one of its possible consequences is diabetic foot syndrome. First level of care physicians should know the clinical behavior of diabetic neuropathy and, above all, how it influences the appearance and development of diabetic foot syndrome. Objective: To describe the role of diabetic neuropathy in the appearance and development of diabetic foot syndrome. Methods: To obtain the information, SciELO, PubMed and Google Scholar were used as search engines for scientific information. The keywords used were: diabetes mellitus; diabetic neuropathy; diabetic foot; diabetic foot syndrome; diabetic foot ulcer; diabetic foot attack. Different review papers, research papers and web pages were evaluated and articles that were more than 10 years old and published in languages other than Spanish, Portuguese and English and that did not refer to the subject of the study through the title were excluded. This allowed the citation of 45 bibliographic references. Conclusions: Diabetic neuropathy constitutes the main risk factor in the appearance and development of diabetic foot syndrome, especially when associated with arthropathy (foot defects), peripheral vascular disease and/or sepsis. Glycemic control, early detection of the foot at risk and preventive care of the lower limbs will have a favorable impact on the patient's health and well-being(AU)

Algunos elementos de interés acerca del diagnóstico y tratamiento de la tormenta tirotóxica / Some elements of interest about the diagnosis and treatment of thyrotoxic storm

Introducción: La tormenta tirotóxica se produce por la liberación repentina y rápida de hormonas tiroideas al torrente sanguíneo. Constituye la complicación más peligrosa de la tirotoxicosis. Objetivo: Describir los principales elementos de interés acerca del diagnóstico y del tratamiento de la tormenta tirotóxica. Métodos: Se utilizaron como motores de búsqueda los correspondientes a las bases de datos Google Académico, Pubmed y SciELO. Las palabras clave utilizadas fueron: tormenta tirotóxica, tormenta tiroidea, tirotoxicosis, hipertiroidismo, diagnóstico y tratamiento. Se evaluaron y se incluyeron los trabajos de revisión, de investigación y las páginas web que tuvieran menos de 10 años de publicados y que por el título trataban el tema de estudio. Fueron excluidos los artículos que no estuvieran en idioma español, portugués o inglés. En total 34 artículos fueran referenciados. Conclusiones: El diagnóstico es eminentemente clínico y se realiza por la detección de factores desencadenantes. Se suma la exacerbación del cuadro clínico de tirotoxicosis previamente existente, el cual afecta a varios sistemas del organismo como consecuencia del aumento de las hormonas tiroideas circulantes. Lo ideal es prevenir la tormenta tirotóxica, aunque ya establecido el tratamiento no se debe retrasar la terapia de la causa desencadenante y de la causa específica. Deberá estar encaminada a reducir la síntesis y la secreción de las hormonas tiroideas y a minimizar las acciones periféricas de estas. Deberán emplearse diferentes fármacos y otras medidas terapéuticas para tratar las complicaciones sistémicas para complementar el tratamiento(AU)

Introduction: Thyrotoxic storm is caused by the sudden and rapid release of thyroid hormones into the bloodstream. It is the most dangerous complication of thyrotoxicosis. Objective: Describe some elements of interest about the diagnosis and treatment of thyrotoxic storm. Methods: Search engines corresponding to Google Scholar, Pubmed and SciELO databases were used. The keywords used were: thyrotoxic storm; thyroid storm; thyrotoxicosis; hyperthyroidism; diagnosis and treatment. The review papers, research papers and web pages, which in general, had less than 10 years of publication and that by the title dealt with the subject of study were evaluated and included. Articles that were not in Spanish, Portuguese or English were excluded. A total of 34 articles were referenced. Conclusions: The diagnosis is eminently clinical and is made by the detection of triggers, to which is added the exacerbation of the clinical picture of thyrotoxicosis previously existing, which affects several systems of the body as a result of the circulating thyroid hormones increase. The ideal is to prevent the thyrotoxic storm; although if the treatment is already established, the therapy of the triggering cause and the specific cause should not be delayed. It should be aimed at reducing the synthesis and secretion of thyroid hormones and minimizing their peripheral actions. Different drugs and other therapeutic measures should be used to treat systemic complications to complement treatment(AU)

Elementos básicos para el diagnóstico y manejo terapéutico del coma mixedematoso en el paciente adulto / Basic elements for the diagnosis and therapeutic management of myxedematous coma in adult patients

Introducción: A pesar de su baja incidencia, la gravedad del cuadro clínico y la alta mortalidad hacen del coma mixedematoso una complicación a tener en cuenta. Objetivo: Describir los elementos básicos para el diagnóstico y manejo terapéutico del coma mixedematoso en el paciente adulto. Métodos: Se realizó una búsqueda de literatura relevante sobre el tema. Se utilizaron buscadores de información científica como Pubmed y Google Académico. La estrategia de búsqueda incluyó los siguientes términos como palabras clave: hipotiroidismo primario, hipotiroidismo subclínico, diagnóstico y tratamiento. Fueron evaluados artículos de revisión, de investigación y páginas web que tuvieran menos de 10 años de publicados. Se consideraron los textos en idioma español e inglés y que hicieran referencia específicamente al tema de estudio a través del título. Fueron excluidos los artículos que no cumplieron con estas condiciones. Esto permitió el estudio de 64 artículos, de los cuales 40 fueron referenciados. Conclusiones: Para el diagnóstico del coma mixedematoso en el paciente adulto lo más importante es sospecharlo en aquellas personas que presenten factores precipitantes, acompañados de síntomas y signos de hipotiroidismo severo con diferentes grados de insuficiencia del sistema nervioso central, hipotermia, hipoventilación, insuficiencia circulatoria e hiponatremia. A esto se sumaría el escenario humoral característico y los posibles hallazgos dependientes de la enfermedad causante del hipotiroidismo. Se debe tratar con un reemplazo agresivo de levotiroxina sódica (vía endovenosa u oral, según posibilidades), unido a otras medidas de apoyo en el entorno hospitalario(AU)

Introduction: Despite its low incidence, the severity of the clinical picture and the high mortality make myxedematous coma a complication to be taken into account. Objective: Describe the basic elements for the diagnosis and therapeutic management of myxedematous coma in adult patients. Methods: A search of relevant literature on the subject was carried out. Pubmed and Google Scholar were used as search engines for scientific information. The search strategy included the following keyword terms: primary hypothyroidism, subclinical hypothyroidism, diagnosis and treatment. Review articles, research articles and Web pages that, in general, had less than 10 years of publication, in Spanish and English that specifically referred to the subject of study through the title were evaluated. Articles that did not meet these conditions were excluded. This allowed the study of 64 articles, of which 40 were referenced. Conclusions: For the diagnosis of myxedematous coma in the adult patient, the most important thing is to suspect it in those people who present precipitating factors, accompanied by symptoms and signs of severe hypothyroidism with different degrees of central nervous system insufficiency, hypothermia, hypoventilation, circulatory insufficiency and hyponatremia. To this would be added the characteristic humoral scenario and the possible findings dependent on the disease causing hypothyroidism. It should be treated with an aggressive replacement of levothyroxine sodium (intravenous or oral way, accodring to the possibilities), together with other supportive measures in the hospital setting(AU)

Elementos básicos para el diagnóstico y manejo terapéutico del hipotiroidismo primario en el paciente adulto / Basic Elements for the Diagnosis and Treatment of Primary Hypothyroidism in the Adult Patient

Introducción: El hipotiroidismo primario, con frecuencia, es diagnosticado de forma tardía y no siempre las dosis indicadas de levotiroxina son las más convenientes. Urge llamar la atención sobre estos aspectos y actualizar el conocimiento sobre este tema. Objetivo: Describir los elementos básicos para el diagnóstico y manejo terapéutico del hipotiroidismo primario en el paciente adulto, en el primer nivel de atención. Métodos: Se realizó una búsqueda de literatura relevante sobre el tema. Se utilizaron como buscadores de información científica a Pubmed y a Google Académico. La estrategia de búsqueda incluyó los siguientes términos como palabras claves: hipotiroidismo primario; hipotiroidismo subclínico; diagnóstico y tratamiento. Fueron evaluados artículos que, en general, tenían menos de 10 años de publicados, en idioma español e inglés, que hicieran referencia específicamente al tema de estudio a través del título. Fueron excluidos los artículos que no cumplieron con estas condiciones. Esto permitió que 72 fueran referenciados. Conclusiones: Para realizar el diagnóstico del hipotiroidismo primario, es fundamental conocer los factores de riesgo y el cuadro clínico correspondiente. La elevación de la tirotropina en suero es la mejor prueba diagnóstica y casi siempre indica la presencia de hipotiroidismo primario. Se debe tener presente al inicio del tratamiento, la edad del paciente, el tiempo de evolución de la enfermedad, la intensidad del hipotiroidismo, el momento fisiológico y la presencia de enfermedades asociadas. Todos los pacientes con hipotiroidismo primario manifiesto deben ser tratados con levotiroxina sódica, pero aquellos con hipotiroidismo subclínico no siempre se benefician con este tratamiento(AU)

Introduction: Primary hypothyroidism is often diagnosed lately and not always are the indicated doses of levothyroxine the most convenient. It is urgent to draw attention towards these aspects and to update knowledge on this subject. Objective: To describe the basic elements for the diagnosis and therapeutic management of primary hypothyroidism in adult patients at the first level of care. Methods: A search for relevant literature on the subject was carried out. Pubmed and Google Scholar were used as search engines for retrieving scientific information. The search strategy included the following terms as keywords: hipotiroidismo primario [primary hypothyroidism], hipotiroidismo subclínico [subclinical hypothyroidism], diagnóstico y tratamiento [diagnosis and treatment]. Generally speaking, articles within ten years of having been published were assessed, written in Spanish and English and making a specific reference to the subject of the study in their respective titles. Articles not meeting these conditions were excluded. This allowed for 72 articles be referenced. Conclusions: To make the diagnosis of primary hypothyroidism, it is essential to know the risk factors and the corresponding clinical picture. Serum thyrotropin elevation is the best diagnostic test and almost always indicates the presence of primary hypothyroidism. The patient's age, the time of evolution of the disease, the intensity of the hypothyroidism, the physiologic time and the presence of associated diseases should be taken into account at the beginning of treatment. All patients with overt primary hypothyroidism should be treated with levothyroxine sodium, but those with subclinical hypothyroidism do not always benefit from this treatment(AU)