Lavados por aspiración colonoscópica para el perfil metataxonómico mucoso de las alteraciones del tracto gastrointestinal asociadas a la espondiloartritis

El estudio de la microbiota del tracto GI de pacientes con espondiloartritis (SpA) se ha centrado en el análisis de muestras de heces, que retratan principalmente la microbiota luminal. El objetivo de este estudio era determinar la contribución de la microbiota de la mucosa y la microbiota luminal a la disbiosis intestinal en la espondiloartritis, utilizando lavados por aspiración colonoscópica (LAC), una alternativa reciente para los estudios regionales del tracto gastrointestinal. Se analizaron 59 CAL (de colon sigmoide e íleon distal), y 41 muestras de heces, de 32 pacientes con SpA y 7 individuos sanos, utilizando perfiles metataxonómicos dirigidos al gen 16S rRNA. Se halló una alta prevalencia de manifestaciones del tracto gastrointestinal entre los pacientes con SpA (65,3%). El perfil metataxonómico confirmó que las muestras de CAL del tracto GI inferior (colon o íleon) presentaban un bacterioma distintivo e indiferenciado, distinto del encontrado en las muestras de heces o en el inicio del tracto GI (cavidad oral [OC]). Las muestras del tracto gastrointestinal inferior y las heces de los pacientes con EI mostraron un comportamiento similar al de la microbiota del grupo con EII, con una riqueza y diversidad microbianas reducidas, en comparación con los controles sanos. Curiosamente, se observó un aumento de los taxones proinflamatorios en los pacientes con EI, como la familia Enterobacteriaceae (principalmente en el íleon), Succinivibrio spp. y Prevotella stercorea. Por el contrario, los pacientes con EA presentaron una disminución significativa de los productores de AGCC Coprococcus catus y Eubacterium biforme. Nuestros datos apoyan el valor de las muestras de CAL para el estudio regional del tracto gastrointestinal y aportan información sobre los posibles "taxones perturbadores" implicados en los trastornos asociados al tracto gastrointestinal observados en los pacientes con SpA.he study of the GI-tract microbiota of spondylarthritis (SpA) patients has focused on the analysis of feces samples, that picture mostly the luminal microbiota. The aim of this study was to determine the contribution of mucosal and luminal microbiome to the gut dysbiosis in SpA, using colonoscopy aspiration lavages (CAL), a recent alternative for regional studies of the GI-tract. We analyzed 59 CAL (from sigmoid colon and distal ileum), and 41 feces samples, from 32 SpA patients and 7 healthy individuals, using 16S rRNA gene-targeted metataxonomic profiling. It was found high prevalence of GI-tract manifestations among SpA patients (65.3%). Metataxonomic profiling, confirmed CAL samples from the lower GI tract (colon or ileum) presented a distinctive and undifferentiated bacteriome and separate from that found in feces’ samples or in the beginning of the GI tract (oral cavity (OC)). Lower GI-tract samples and feces of SpA patients exhibited similar behavior to the microbiota of IBD group with reduced microbial richness and diversity, comparing to the healthy controls. Interestingly, it was found increase in proinflammatory taxa in SpA patients, such as Enterobacteriaceae family (mostly in the ileum), Succinivibrio spp. and Prevotella stercorea. Conversely, SpA patients presented significant decrease in the SCFA producers Coprococcus catus and Eubacterium biforme. Our data support the value of CAL samples for the regional study of GI-tract and contribute with information of potential “disruptor taxa” involved in the GI-tract associated disorders observed in SpA patients

Niveles elevados de leptina y adipsina se asocian con la actividad clínica en pacientes con artritis reumatoide temprana con sobrepeso e infección periodontal

Las adipocinas están asociadas a la patogénesis de la artritis reumatoide (AR) y son biomarcadores potenciales de la actividad de la enfermedad, la periodontitis y la obesidad. El objetivo era establecer la asociación entre el perfil de adipocinas, la actividad de la enfermedad de la AR, el índice de masa corporal y la infección periodontal. En este estudio se evaluaron 51 pacientes con AR temprana y 51 controles, incluyendo marcadores reumatológicos séricos, niveles de adipocinas, detección de Porphyromonas gingivalis y anticuerpos séricos anti-Porphyromonas gingivalis, y mediciones clínicas y periodontales. Se realizaron análisis estadísticos con SPSS® V26, con un modelo de regresión logística para confirmar las asociaciones. Los resultados muestran que los niveles elevados de leptina eran más frecuentes en pacientes (p = 0,001) que presentaban simultáneamente una mayor frecuencia de Porphyromonas gingivalis (p = 0,004). Los pacientes con presencia concomitante de Porphyromonas gingivalis, alta puntuación de actividad clínica y sobrepeso se correlacionaron con altos niveles de leptina (OR, 7,20; IC 95%, 2,68-19,33; p = 0,0001) y adipsina (OR, 2,69; IC 95%, 1,00-7,28; p = 0,005). La conclusión es que los niveles elevados de leptina y adipsina se asocian a una mayor actividad clínica en pacientes con AR temprana con sobrepeso e infección periodontal, por lo que el sobrepeso y Porphyromonas gingivalis pueden potenciar la actividad de la AR. Esto puede representar un mecanismo patológico entre estas condiciones, donde las adipokinas parecen tener un papel clave.Adipokines are associated with the pathogenesis of rheumatoid arthritis (RA) and are potential biomarkers of disease activity, periodontitis, and obesity. The aim of this was to establish the association between adipokine profile, RA disease activity, body mass index, and periodontal infection. This study evaluated 51 patients with early-RA and 51 controls including serum rheumatological markers, adipokine levels, detection of Porphyromonas gingivalis and serum anti-Porphyromonas gingivalis antibodies, clinical and periodontal measurements. Statistical analyses were run with SPSS® V26, with a logistic regression model to confirm associations. The results show high levels of leptin were more frequent in patients (p = 0.001) who simultaneously showed a higher frequency of Porphyromonas gingivalis (p = 0.004). Patients with concomitant presence of Porphyromonas gingivalis, high clinical activity score, and overweight were correlated with high levels of leptin (OR, 7.20; 95% CI, 2.68–19.33; p = 0.0001) and adipsin (OR, 2.69; 95% CI, 1.00–7.28; p = 0.005). The conclusion is that high levels of leptin and adipsin are associated with greater clinical activity in early-RA patients with overweight and periodontal infection, whereby overweight and Porphyromonas gingivalis may enhance RA activity. This may represent a pathological mechanism between these conditions, where adipokines seem to have a key role

Predictive factors related to the progression of periodontal disease in patients with early rheumatoid arthritis: A cohort study

Background: Rheumatoid arthritis (RA) and periodontal disease are inter-related conditions. However, factors predictive of periodontal disease progression in patients with early rheumatoid arthritis (eRA) are lacking. The aim of this study was to identify factors associated with the progression of clinical attachment loss (CAL) in interproximal dental sites of eRA patients. Methods: Twenty-eight eRA patients were evaluated for the progression of CAL at 280 interproximal dental sites at 1 year of follow-up. Markers of RA activity (rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein), a marker of bone resorption (Dickkopf-related protein 1), Disease Activity Score 28 and Simple Disease Activity Index were included as potential systemic predictive factors. Plaque index, gingival index, pocket depth, clinical attachment level and Dickkopf-related protein 1 in crevicular fluid at baseline were included as potential local predictive factors. Data were analysed in a hierarchical structure using generalised linear mixed models for progression at each site (> 2 mm) during follow-up. Results: C-reactive protein level was the most important predictive systemic factor for the progression of CAL. The mean CAL and a high degree of gingival inflammation in interproximal sites at baseline were important predictive local factors (p < 0.0001). Patients who received combined treatment with disease-modifying antirheumatic drugs and corticosteroids exhibited less CAL (p < 0.0001). The predictive value of the generalised linear mixed model for progression was 85%. Conclusions: Systemic factors, including RA disease activity and baseline periodontal condition, were associated with periodontal progression. Pharmacological treatment may affect periodontal progression in patients with early RA

El efecto de interacción de los títulos de anticuerpos anti-RgpA y anti-PPAD: Un indicador para el diagnóstico de la artritis reumatoide

Porphyromonas gingivalis secreta factores de virulencia como Arg-gingipains y peptidil arginina deiminasa (PPAD), que están asociados con la patogénesis de la artritis reumatoide (AR). Sin embargo, no existe información sobre los títulos de anticuerpos frente a estas enzimas bacterianas como indicadores sistémicos o biomarcadores en la AR. En este estudio transversal se evaluó a 255 individuos: 143 con diagnóstico de AR y 112 sin AR. Se utilizaron modelos de regresión logística ajustados por edad, sexo, índice metabólico basal, tabaquismo y gravedad de la periodontitis para evaluar la asociación de la AR con el factor reumatoide (FR), los anticuerpos antiproteínas citrulinadas (ACPA), la velocidad de sedimentación globular, la proteína C reactiva de alta sensibilidad, los anti-RgpA, los anti-PPAD y los anti-RgpA/anti-PPAD doblemente positivos. Se observó que el FR (odds ratio [OR] 10,6; intervalo de confianza [IC] del 95%: 4,4-25), los ACPA (OR 13,7; IC del 95%: 5,1-35) y la doble positividad anti-RgpA/anti-PPAD (OR 6,63; IC del 95%: 1,61-27) se asociaban con el diagnóstico de AR. Los anti-RgpA también se asociaron con la AR (OR 4,09; IC 95%: 1,2-13,9). La combinación de anti-RgpA/anti-PPAD mostró una elevada especificidad del 93,7% y un VPP del 82,5% en la identificación de individuos con AR. Los anticuerpos anti-RgpA se asociaron con el índice inflamatorio periodontal en individuos con AR (p < 0,05). La doble positividad de los anticuerpos anti-RgpA/anti-PPAD mejoró el diagnóstico de AR. Por lo tanto, los anticuerpos RgpA y anti-RgpA/anti-PPAD pueden ser biomarcadores de la AR.Porphyromonas gingivalis secretes virulence factors like Arg-gingipains and peptidyl arginine deiminase (PPAD), that are associated with rheumatoid arthritis (RA) pathogenesis. However, there is no information regarding the antibody titers for these bacterial enzymes as systemic indicators or biomarkers in RA. In this cross-sectional study, 255 individuals were evaluated: 143 were diagnosed with RA, and 112 were without RA. Logistic regression models adjusted for age, sex, basal metabolic index, smoking, and periodontitis severity were used to evaluate the association of RA with rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs), erythrocyte sedimentation rate, high sensitivity C-reactive protein, anti-RgpA, anti-PPAD, and double positive anti-RgpA/anti-PPAD. It was found that RF (odds ratio [OR] 10.6; 95% confidence interval [CI] 4.4–25), ACPAs (OR 13.7; 95% CI 5.1–35), and anti-RgpA/anti-PPAD double positivity (OR 6.63; 95% CI 1.61–27) were associated with RA diagnoses. Anti-RgpA was also associated with RA (OR 4.09; 95% CI 1.2–13.9). The combination of anti-RgpA/anti-PPAD showed a high specificity of 93.7% and 82.5% PPV in identifying individuals with RA. RgpA antibodies were associated with the periodontal inflammatory index in RA individuals (p < 0.05). The double positivity of the anti-RgpA/anti-PPAD antibodies enhanced the diagnosis of RA. Therefore, RgpA antibodies and anti-RgpA/anti-PPAD may be biomarkers for R

Aplicación de criterios de cribado de la enfermedad inflamatoria intestinal en pacientes con espondiloartritis y su asociación con la enfermedad y la actividad endoscópica

Existe poca bibliografía sobre la aplicación de criterios de cribado de la enfermedad inflamatoria intestinal (EII) en pacientes con espondiloartritis (EPS). Este estudio tenía como objetivo aplicar criterios de cribado de EII en un grupo de pacientes con EspA sin diagnóstico de EII y correlacionarlos con los hallazgos endoscópicos y la actividad de la enfermedad. Se incluyó a un total de 82 pacientes con EspA. Se realizó la prueba de cribado de la EII y una ileocolonoscopia con cromoendoscopia digital con aumento y análisis histológico. Los datos se analizaron con la prueba de Chi-cuadrado/prueba exacta de Fisher y análisis de correspondencias múltiples. Los principales criterios de cribado encontrados en el 48,7% de los pacientes estaban asociados a antecedentes de infección (p = 0,037). La hemorragia rectal se asoció al diagnóstico de espondilitis anquilosante, inflamación aguda, entesitis y alteración de la arquitectura tisular en el íleon (p < 0,050). La diarrea se asoció a una mayor puntuación de la actividad de la enfermedad (p = 0,02). Los criterios de cribado menores se asociaron con una articulación inflamatoria dolorosa (p = 0,05), una puntuación elevada de la actividad de la enfermedad (p = 0,001) y niveles elevados de calprotectina (p = 0,050). El dolor abdominal (36,9%) se asoció con compromiso axial/periférico (p = 0,017), dolor lumbar inflamatorio (p = 0,01), entesitis (p = 0,021), mayor puntuación de actividad de la enfermedad (p = 0,023) e inflamación aguda del íleon (p = 0,046). La diarrea de 4 semanas y el dolor abdominal fueron los criterios de cribado mayor y menor más prevalentes, respectivamente, estando relacionados con manifestaciones tempranas de compromiso inflamatorio intestinal y mayor puntuación de actividad de la enfermedad. Esta prueba de cribado ofrece la posibilidad de derivar oportunamente a los pacientes con EAE de reumatología a gastroenterología.There is little literature on the implementation of screening criteria for inflammatory bowel disease (IBD) in patients with spondyloarthritis (SpA). This study aimed to apply IBD screening criteria in a group of patients with SpA without IBD diagnosis and correlate them to endoscopic findings and disease activity. A total of 82 patients with SpA were included. The IBD screening test and ileocolonoscopy with digital chromoendoscopy with magnification and histological analysis were performed. The data were analysed with Chi-square test/Fisher’s exact test and multiple correspondence analysis. The major screening criteria found in 48.7% of the patients were associated with a history of infection (p = 0.037). Rectal bleeding was associated with the diagnosis of ankylosing spondylitis, acute inflammation, enthesitis and tissue architecture alteration in the ileum (p < 0.050). Diarrhoea was associated with a higher disease activity score (p = 0.02). Minor screening criteria were associated with painful inflammatory joint (p = 0.05), high disease activity score (p = 0.001) and high calprotectin levels (p = 0.050). Abdominal pain (36.9%) was associated with axial/peripheral compromise (p = 0.017), inflammatory back pain (p = 0.01), enthesitis (p = 0.021), higher disease activity score (p = 0.023) and acute ileum inflammation (p = 0.046). Diarrhoea of 4 weeks and abdominal pain were the most prevalent major and minor screening criteria, respectively, being related to early manifestations of inflammatory bowel compromise and higher disease activity score. This screening test grants a chance of opportune referral of SpA patients from rheumatology to gastroenterology

Survival benefits of kidney transplantation with expanded criteria deceased donors in patients aged 60 years and over.

International audienceBACKGROUND: The proportion of transplant candidates aged 60 years and over listed on the kidney transplant waiting list is increasing, as is the proportion of potential organ donors of this age. We compared in elderly recipients: kidney graft survival of expanded criteria deceased donor (ECD) to nonexpanded criteria deceased donor (NECD), and survival of patients receiving these grafts to those remaining on the waiting list. METHODS: Between 1996 and 2004, a total of 3001 patients aged 60 years and over were registered on the French kidney transplant waiting list, of which 2099 were transplanted. The data were analyzed using Kaplan-Meier methods and Cox models. RESULTS: ECD was defined as presenting at least one of the following factors: age over 60 years than less (relative risk [RR]=1.26; P=0.02), history of arterial hypertension vs. absence (RR=1.34; P=0.01), history of diabetes mellitus vs. absence (RR=1.6; P=0.01), and death due to cerebrovascular accident vs. other cause (RR=1.3; P=0.01). Patients who did not undergo transplantation had an adjusted risk of death 2.54 times higher than that of transplanted patients of the same age (P<0.0001), regardless of the type of graft. The risk was 3.78 times higher than that for patients receiving NECD grafts (P<0.0001) and 2.31 for patients receiving ECD grafts (P<0.0001). CONCLUSION: In elderly patients, transplantation with an ECD kidney was associated with higher survival rates than remaining on the waiting list. This result suggests that the identification and use of ECD kidney grafts should be optimized, given changes in the characteristics of potential donors and recipients

Calcificación y osificación extra esqueléticas: Calcinosis, calcergia y calcifilaxis

La calcificación y osificación extraesqueléticas son patologías que observamos frecuentemente en la práctica clínica. Sin embargo, existen pocos informes en la literatura médica y el conocimiento acerca de estas entidades es aun muy precario

A Predictive Microsimulation Model to Estimate the Clinical Relevance of Reducing Alcohol Consumption in Alcohol Dependence

Background: Alcohol consumption is one of the most important factors for disease and disability in Europe. In clinical trials, nalmefene has resulted in a significant reduction in the number of heavy-drinking days (HDDs) per month and total alcohol consumption (TAC) among alcohol-dependent patients versus placebo. Methods: A microsimulation model was developed to estimate alcohol-attributable diseases and injuries in patients with alcohol dependence and to explore the clinical relevance of reducing alcohol consumption. Results: For all diseases and injuries considered, the number of events (inpatient episodes) increased with the number of HDDs and TAC per year. The model predicted that a reduction of 20 HDDs per year would result in 941 fewer alcohol-attributable events per 100,000 patients, while a reduction in intake of 3,000 g/year of pure alcohol (ethanol) would result in 1,325 fewer events per 100,000 patients. Conclusion: The potential gains of reducing consumption in alcohol-dependent patients were considerable

Are obesity, ACPAs and periodontitis conditions that influence the risk of developing rheumatoid arthritis in first-degree relatives?

The aim of this study was to investigate the body mass index (BMI), anti-citrullinated protein antibodies (ACPAs) status and the presence of periodontitis and IgG-1/IgG-2 antibodies against Porphyromonas gingivalis (Pg) in the first-degree relatives (FDRs) of rheumatoid arthritis (RA) patients and compare these variables with a control group of healthy individuals from the general population. In total, 100 FDR individuals and 200 healthy controls matched by age and gender were included. Rheumatologic and periodontal assessment was performed, and the presence of ACPAs and anti-P. gingivalis antibodies was evaluated. Groupwise comparisons were analysed using the McNemar and Wilcoxon tests. A conditional logistic regression analysis was performed to establish the associations between BMI, ACPAs and periodontitis in both groups. In the FDR group, 70% of the subjects were female, with a mean age of 37.3 ± 13 years. Obesity was observed in 17 and 7% of the FDRs and controls, respectively. ACPAs were found in 7% of the FDRs vs. 2.5% of the controls. Periodontitis was diagnosed in 79 and 56% of the FDRs and controls, respectively. Among the FDRs, 15% had severe periodontitis. There were associations in the FDR group related to the presence of obesity (OR 2.93, 95% CI 1.03–8.28), ACPAs (OR 2.45, 95% CI 0.7–8.32) and periodontitis (OR 3.70 95% CI 1.89–7.29). Regarding anti-P. gingivalis antibodies and smoking history, no differences were found between the groups. Obesity, ACPAs and periodontitis (diagnosis and severity) can be considered as relevant conditions associated with the development of RA in FDRs

Polyautoimmunity and familial autoimmunity in systemic sclerosis

"Characterization of the extent to which particular combinations of autoimmune diseases occur in excess of that expected by chance may offer new insights into possible common pathophysiological mechanisms. The goal of this study was to investigate the spectrum of polyautoimmunity (i.e. autoimmune diseases co-occurring within patients) and familial autoimmunity (i.e. diverse autoimmune diseases co-occurring within families) in patients with systemic sclerosis (SSc). A cross-sectional study of two convenience samples of patients with SSc, one in Canada and the other in Colombia, was performed. History of other autoimmune diseases in the SSc patients as well as a family history of autoimmunity was obtained. Of 719 patients, 273 (38%) had at least one other autoimmune disease. A total of 366 autoimmune diseases were reported, of which the most frequent were autoimmune thyroid disease (AITD, 38%), rheumatoid arthritis (RA, 21%), Sjögren's syndrome (18%), and primary biliary cirrhosis (4%). There were 260 (36%) patients with first-degree relatives with at least one autoimmune disease, of which the most frequent were RA (18%) and AITD (9%). Having at least one first-degree relative with autoimmune disease was a significant predictor of polyautoimmunity in SSc patients. No significant differences in polyautoimmunity or familial autoimmunity were noted between diffuse and limited subsets of disease. Our results indicate that polyautoimmunity is frequent in patients with SSc and autoimmune diseases cluster within families of these patients. Clinically different autoimmune phenotypes might share common susceptibility variants, which acting in epistatic pleiotropy may represent risk factors for autoimmunity. © 2008 Elsevier Ltd. All rights reserved.