Molecular maps of synovial cells in inflammatory arthritis using an optimized synovial tissue dissociation protocol.

In this study, we optimized the dissociation of synovial tissue biopsies for single-cell omics studies and created a single-cell atlas of human synovium in inflammatory arthritis. The optimized protocol allowed consistent isolation of highly viable cells from tiny fresh synovial biopsies, minimizing the synovial biopsy drop-out rate. The synovium scRNA-seq atlas contained over 100,000 unsorted synovial cells from 25 synovial tissues affected by inflammatory arthritis, including 16 structural, 11 lymphoid, and 15 myeloid cell clusters. This synovial cell map expanded the diversity of synovial cell types/states, detected synovial neutrophils, and broadened synovial endothelial cell classification. We revealed tissue-resident macrophage subsets with proposed matrix-sensing (FOLR2+COLEC12high) and iron-recycling (LYVE1+SLC40A1+) activities and identified fibroblast subsets with proposed functions in cartilage breakdown (SOD2highSAA1+SAA2+SDC4+) and extracellular matrix remodeling (SERPINE1+COL5A3+LOXL2+). Our study offers an efficient synovium dissociation method and a reference scRNA-seq resource, that advances the current understanding of synovial cell heterogeneity in inflammatory arthritis.

Cancer-associated myositis before and after the COVID-19 pandemic onset: a changing trend.

OBJECTIVES: During the COVID-19 pandemic, there was a significant impact on the management of non-COVID-19 related diseases, potentially increasing the incidence of paraneoplastic syndromes such as cancer-associated myositis (CAM).The aim of this study is to determine the incidence of CAM in our cohort before and after the COVID-19 pandemic onset. METHODS: We included patients with idiopathic inflammatory myopathy (IIM), diagnosed between June 2016 and June 2023. The patients were divided into two groups according to the date of IIM diagnosis. RESULTS: We included 132 patients; 65.1% (n=86) were diagnosed prior to and 34.9% (n=46) after the COVID-19 pandemic. The most common IIM was dermatomyositis (DM) before and after the COVID-19 pandemic onset (p=0.750). The most frequent myositis-specific antibody (MSA) before the COVID-19 pandemic was anti-Mi2 (15.1%). After the COVID-19 pandemic onset, anti-TIF1γ was the most common MSA (21.7%), with a significantly higher relative prevalence (p=0.006). The incidence of CAM was significantly higher after the COVID-19 pandemic onset (11 vs. 3 new cases, p<0.002). Patients with CAM more frequently had anti-TIF1γ-positivity (p<0.001) and a diagnosis after the pandemic (p=0.001) than non-CAM-IIM patients. No significant differences were found regarding vaccination status or previous COVID-19 infection in CAM and non-CAM-IIM patients. Diagnosis after the COVID-19 pandemic was an independent predictor of CAM among IIM patients (OR 0.012, 95% CI 0.000-0.400, p=0.013), regardless of age, sex or previous COVID-19 infection. CONCLUSIONS: There was a significant increase in the incidence of CAM after the COVID-19 pandemic. IIM diagnosis after the COVID-19 pandemic was an independent predictor of CAM.

Ultrasound-Guided Synovial Biopsy: A Review.

Ultrasound-guided synovial biopsy is a safe, well-tolerated, and effective method to collect good-quality synovial tissue from all types of joints for clinical and research purposes. Although synovial biopsy cannot be used to distinguish between types of inflammatory rheumatic disease, analysis of synovial tissue has led to remarkable advances in the understanding of the pathobiology of rheumatoid arthritis and other inflammatory rheumatic diseases. Synovitis is the hallmark of these diseases; hence, accessing the core of the pathological process, synovial tissue, provides an opportunity to gather information with potential diagnostic and prognostic utility.

Efficacy, Safety, and Sample Quality of Ultrasound-Guided Synovial Needle Biopsy in Clinical Practice and Research: A Prospective Observational Study.

OBJECTIVE: To study the efficacy, tolerability, safety, and sampling variation of ultrasound (US)-guided synovial biopsies performed in clinical practice and research. METHODS: We included all patients who had a US-guided synovial needle biopsy from November 2013 to January 2018. Patients were evaluated for procedure safety and tolerability. Usefulness of synovial biopsy was considered based on contribution for achieving the proposed aims. We analyzed samples for presence and quality of synovial tissue, synovitis score/grade, and pathotype. Variation across patients, samples, section levels, and sampling order was assessed. RESULTS: A total of 64 US-guided synovial biopsies were performed (n = 52 in clinical practice, n = 12 in research). Patient tolerability (70% no/mild discomfort) was remarkably high. There was no significant aggravation of symptoms or US synovitis in the biopsied joint. Procedures were overall safe, with few minor, 2 moderate, and no major adverse events. Usefulness of US-guided synovial biopsies was high, both in clinical practice (37% direct diagnostic impact, 100% positive/95% negative predictive values for infection) and in research (92% success). Synovial tissue was retrieved in 88% of biopsies, with a median of 75% gradable samples. There was significant variation in sample quality and synovitis features across patients and samples, but not between different section levels. Samples collected later in the procedure had a lower frequency of synovial tissue and were poorly concordant in pathotype with those collected earlier. CONCLUSION: US-guided synovial needle biopsy is an effective, safe, and well-tolerated means to collect good quality synovial tissue for clinical and research purposes. Samples collected for different aims should be retrieved in parallel, rather than sequentially.

A low fermentable oligo-di-mono-saccharides and polyols (FODMAP) diet is a balanced therapy for fibromyalgia with nutritional and symptomatic benefits

INTRODUCTION: Fibromyalgia is a chronic rheumatic disease producing widespread pain, associated to a major comorbidity -irritable bowel syndrome. Low FODMAPS diet (low fermentable oligo-di-mono-saccharides and polyols diet) has been effective in controlling irritable bowel syndrome symptoms. Overweight is an aggravating factor for fibromyalgia. We studied effects of low fermentable oligo-di-mono-saccharides and polyols diets on fibromyalgia symptoms and weight status. METHODS: A longitudinal study was performed on 38 fibromyalgia patients using a four-week, repeated assessment as follow: M1 = first assessments/presentation of individual low fermentable oligo-di-mono-saccharides and polyols diet; M2 = second assessments/reintroduction of FODMAPs; M3 = final assessments/nutritional counselling. The assessment instruments applied were: Fibromyalgia Survey Questionnaire (FSQ); Severity Score System (IBS-SSS); visual analogic scale (VAS). Body mass-index/composition and waist circumference (WC) were also measured. Daily macro-micronutrients and FODMAP intake were quantified at each moment of the study. RESULTS: The studied cohort was 37% overweight, 34% obese (average body mass-index 27.4 ± 4.6; excess fat mass 39.4 ± 7%). Weight, body mass-index and waist circumference decreased significantly (p < 0.01) with low fermentable oligo-di-mono-saccharides and polyols diet, but no significant effect on body composition was observed. All fibromyalgiasymptoms, including somatic pain, declined significantly post-LFD (p < 0.01); as well for severity of fibromyalgia [Fibromyalgia survey questionnaire: M1 = 21.8; M2 = 16.9; M3 = 17.0 (p < 0.01)]. The intake of essential nutrients (fiber, calcium, magnesium and vitamin D) showed no significant difference. The significant reduction in FODMAP intake (M1 = 24.4 g; M2 = 2.6g; p < 0.01) reflected the "Diet adherence" (85%). "Satisfaction with improvement of symptoms" (76%), showed correlating with "diet adherence" (r = 0.65; p < 0.01). CONCLUSIONS: Results are highly encouraging, showing low fermentable oligo-di-mono-saccharides and polyols diets as a nutritionally balanced approach, contributing to weight loss and reducing the severity of FM fibromyalgiasymptoms.

O impacto da obra de J. B. Watson na psicologia norte-americana: Alguns parâmetros de comparação / The impact of J. B. Watson's work on American Psychology: Some comparison parameters / El impacto de la obra de J. B. Watson en la psicología norteamericana: Algunos parámetros de comparación

O impacto da obra de J. B. Watson tem sido explorado na historiografia da psicologia. Neste âmbito, destacam-se estudos que utilizam como método a análise bibliométrica. Tais pesquisas, no entanto, não utilizam parâmetros comparativos que possam indicar de forma mais precisa o grau de impacto daquela obra. O presente estudo busca preencher tal lacuna por meio de uma análise bibliométrica comparativa das referências às obras de Watson e outros três relevantes psicólogos do período: Edward B. Titchener, Edward L. Thorndike e William James. A pesquisa foi realizada em cinco importantes periódicos norte-americanos da área, entre os anos 1903 e 1923 ­ uma década antes e uma década após a publicação do Manifesto Behaviorista. Os resultados permitem concluir que, embora não possa ser tomada propriamente como um marco revolucionário, a obra de Watson teve, na década posterior à publicação do Manifesto Behaviorista (1914-1923), um impacto próximo ao de Titchener e maior do que o de Thorndike, ainda que distante da influência exercida por James. (AU)

The impact of J. B. Watson's work has been explored in the historiography of psychology. In this context, bibliometric analysis has been often used as a methodological strategy. However, such studies do not present comparative parameters that may indicate more precisely its degree of impact. The goal of this paper is to fill this gap, by making a comparative bibliometric analysis of citations to Watson and three other representative psychologists at that time: Edward B. Titchener, Edward L. Thorndike and William James. Five important American journals were scrutinized for the period between 1903 and 1923, a decade before and a decade after the publication of Watson's Behaviorist Manifesto. The results suggest that, even if it cannot be taken as a revolutionary milestone, Watson's work had, in the first decade after the publication of the Behaviorist Manifesto (1914-1923), an impact similar to Titchener's and higher than Thorndike's, although still distant from James's influence. (AU)

El impacto de la obra de J. B. Watson ha sido investigado en la historiografía de la psicología. En este contexto, se destacan los estudios que utilizan el análisis bibliométrico como método. Sin embargo, estos estudios no utilizan parámetros comparativos que pueden indicar con mejor precisión el grado de impacto del autor. El objetivo de este estudio es llenar este vacío por medio de un análisis bibliométrico comparativo de las citas de las obras de Watson y de otros tres sicólogos importantes en este período: Edward B. Titchener, Edward Thorndike y William James. La búsqueda se realizó en cinco periódicos norteamericanos importantes entre los años 1903 y 1923, una década antes y una década después de la publicación del Manifiesto Conductista de Watson. Los resultados permiten concluir que, aún que no pueda ser tomada propiamente como un hito revolucionario, la obra de Watson tuvo, en la década después de la publicación del Manifiesto Conductista (1914-1923), un impacto próximo al de Titchener y más alto que el de Thorndike, aún que muy distante de la influencia ejercida por James. (AU)

A low fermentable oligo-di-mono saccharides and polyols (FODMAP) diet reduced pain and improved daily life in fibromyalgia patients.

BACKGROUND AND AIMS: Fibromyalgia (FM) is a chronic, rheumatic disease characterized by widespread myofascial pain, of unknown aetiology, having a major impact on quality of life (QOL). Available pharmacotherapy for FM is marginally effective. FM is associated with co-morbidities of gastrointestinal (GI) disorders and Irritable Bowel Syndrome (IBS). There is growing evidence that diets low in FODMAPs, "fermentable oligo-, di- or mono-saccharides and polyols" [Low FODMAP Diet (LFD)], are effective in treating IBS. The aim of this pilot study was to examine the effects of LFDs on symptoms of FM, especially with regard to pain, QOL and GI disorders. METHODS: A longitudinal study using LFD intervention was performed on 38, 51±10 year-old, female patients diagnosed with FM for an average of 10 years, based on ACR (American College of Rheumatology) 2010 criteria. The study was conducted from January through May, 2015, using a four-week, repeated-assessment model, as follows: Moment 0 - introduction of the protocol to participants; Moment 1 - first assessment and delivery of individual LFD dietary plans; Moment 2 - second assessment and reintroduction of FODMAPs; Moment 3 - last assessment and final nutritional counselling. Assessment tools used were the following: RFIQ (Revised Fibromyalgia Impact Questionnaire), FSQ (Fibromyalgia Survey Questionnaire), IBS-SSS (Severity Score System), EQ-5D (Euro-QOL quality of life instrument), and VAS (Visual Analogue Scale). Daily consumption of FODMAPs was quantified based on published food content analyses. Statistical analyses included ANOVA, non-parametric Friedman, t-student and Chi-square tests, using SPSS 22 software. RESULTS: The mean scores of the 38 participants at the beginning of the study were: FSQ (severity of FM, 0-31) - 22±4.4; RFIQ (0-100) - 65±17; IBS-SSS (0-500) - 275±101; and EQ-5D (0-100) - 48±19. Mean adherence to dietary regimens was 86%, confirmed by significant difference in FODMAP intakes (25g/day vs. 2.5g/day; p<0.01). Comparisons between the three moments of assessment showed significant (p<0.01) declines in scores in VAS, FSQ, and RFIQ scores, in all domains measured. An important improvement was observed with a reduction in the severity of GI symptoms, with 50% reduction in IBS scores to 138±117, following LFD therapy. A significant correlation (r=0.36; p<0.05) was found between improvements in FM impact (declined scores) and gastrointestinal scores. There was also a significant correlation (r=0.65; p<0.01) between "satisfaction with improvement" after introduction of LFDs and "diet adherence", with satisfaction of the diet achieving 77% among participants. A significant difference was observed between patients who improved as compared to those that did not improve (Chi-square χ2=6.16; p<.05), showing that the probability of improvement, depends on the severity of the RFIQ score. CONCLUSIONS: Implementation of diet therapy involving FODMAP restrictions, in this cohort of FM patients, resulted in a significant reduction in GI disorders and FM symptoms, including pain scores. These results need to be extended in future larger studies on dietary therapy for treatment of FM. IMPLICATIONS: According to current scientific knowledge, these are the first relevant results found in an intervention with LFD therapy in FM and must be reproduced looking for a future dietetic approach in FM.

Primary biliary cirrhosis in a rheumatoid arthritis patient treated with rituximab, a case-based review.

Primary biliary cirrhosis (PBC) is an autoimmune disease in which intrahepatic bile ducts are targeted by an immune-mediated injury. This disease tends to progress to fibrosis and cirrhosis with hepatic failure. The authors report a case of a 50-year-old rheumatoid arthritis (RA) patient, with erosions and seropositive for rheumatoid factor and anti-citrullinated peptide antibodies, with 18 years disease duration refractory to prednisolone and several disease-modifying antirheumatic drugs, either conventional or biological (adalimumab and etanercept). In April 2007, she started therapy with rituximab (RTX) with good European League Against Rheumatism response achieved 9 months later. In June 2008, she was admitted with intrahepatic cholestasis, steatorrhea, and spontaneous fractures of various ribs. After excluding cholelitiasis, as well as infectious and neoplastic diseases a liver biopsy was performed that was compatible with the diagnosis of PBC. The antinuclear antibodies (1/160) were positive as well as the antimitochondrial antibodies (1/640). Other antibodies were negative such as anti-SSA and anti-SSB. Afterwards, the patient started ursodesoxycholic acid 15 mg kg(-1) day(-1) with progressive improvement of cholestatic markers. A labial salivary gland biopsy was performed and showed findings compatible with the concomitant diagnosis of Sjögren's syndrome. Based on this clinical report, a detailed review of the clinical aspects of PBC is presented as well as its association with other immune-mediated inflammatory diseases, particularly, with RA.

Prevalence of fibromyalgia: a survey in five European countries.

OBJECTIVE: A survey was performed in 5 European countries (France, Germany, Italy, Portugal, and Spain) to estimate the prevalence of fibromyalgia (FM) in the general population. METHODS: In each country, the London Fibromyalgia Epidemiological Study Screening Questionnaire (LFESSQ) was administered by telephone to a representative sample of the community over 15 years of age. A positive screen was defined as the following: (1) meeting the 4-pain criteria alone (LFESSQ-4), or (2) meeting both the 4-pain and the 2-fatigue criteria (LFESSQ-6). The questionnaire was also submitted to all outpatients referred to the 8 participating rheumatology clinics for 1 month. These patients were examined by a rheumatologist to confirm or exclude the FM diagnosis according to the 1990 American College of Rheumatology classification criteria. The prevalence of FM in the general population was estimated by applying the positive-predictive values to eligible community subjects (ie, positive screens). RESULTS: Among rheumatology outpatients, 46% screened positive for chronic widespread pain (LFESSQ-4), 32% for pain and fatigue (LFESSQ-6), and 14% were confirmed FM cases. In the whole general population, 13 and 6.7% screened positive for LFESSQ-4 and LFESSQ-6, respectively. 3The estimated overall prevalence of FM was 4.7% (95% CI: 4.0 to 5.3) and 2.9% (95% CI: 2.4 to 3.4), respectively, in the general population. The prevalence of FM was age- and sex-related and varied among countries. CONCLUSION: FM appears to be a common condition in these 5 European countries, even if data derived from the most specific criteria set (LFESSQ-6) are considered.

Síndrome de Sjõgren primária: manifestações exócrinas e não exócrinas / Primary Sjõgren's syndrome: exocrine and non-exocrine manifestations

Objetivo: caracterizar as manifestações clínicas, exócrinas e não exócrinas, de 74 pacientes com síndrome de Sjõgren primária (SSp). Métodos: estudo retrospectivo dos pacientes com SSp de acordo com os novos critérios americano-europeus de 2002, seguidos no serviço de reumatologia e doenças ósseas metabólicas do Hospital de Santa Maria (HSM) nos últimos 25 anos (média de seguimento de 7,7 anos). Resultados: todos os pacientes apresentaram doença exócrina dos epitélios superficiais, com destaque para xerostomia e a queratoconjuntivite seca. Doença exócrina dos órgãos internos foi encontrada em 25 pacientes (33,8 por cento), enquanto apenas um paciente (1,4 por cento) desenvolveu doença linfocitária B monoclonal (pseudolinfoma pulmonar). Do total, 55 pacientes (74,3 por cento) também apresentaram manifestações não-exócrinas, com predomínio das induzidas por mediadores da inflamação (68,9 por cento). As manifestações vasculares inflamatórias estiveram presentes em 54 por cento dos pacientes e as vasculares não-inflamatórias em 27 por cento. A tiroidite auto-imune surgiu em 5 pacientes (6,8 por cento). Conclusões: os componentes oral e ocular dominam a doença, sendo mais limitadas as manifestações orgânicas graves. Este modelo classificativo permite comparar alterações fisiopatológicas entre os pacientes e abre uma via de estudo para encontrar marcadores de atividade/cronicidade com estas relacionadas.