Conservative Interventions for mobile Pes Planus in Adults: a systematic review

Antecedentes. Pes Adulto planus (pie plano) es un problema común encontrado por muchos profesionales de la salud. A pesar de la percepción de que el pie plano puede causar dolor y deteriorar su función, la disponibilidad y el uso generalizado de diversos tratamientos, no hay consenso sobre la estrategia óptima de tratamiento. Objetivo. Evaluar la efectividad de las intervenciones conservadoras (no quirúrgicos) para pie plano en los adultos. Método. Se realizó una búsqueda sistemática de la literatura. Esto incluye: el Registro Cochrane Central de Ensayos Controlados; los Juicios CMSG Especializados Registro; una búsqueda electrónica se realizó utilizando MEDLINE (1960 a junio de 2012), EMBASE (1980 a junio de 2012), y CINAHL (1982 - junio de 2012). Revistas especializadas, listas de referencias de ensayos y artículos de revisión se realizaron búsquedas manuales. Criterios de selección: Ensayos aleatorios o cuasialeatorios de intervenciones de tratamiento para el pie plano en los adultos. Se excluyeron los ensayos que incluyeron patologías específicas como el dolor plantar del talón, las fracturas por sobrecarga de los metatarsianos, disfunción del tendón tibial posterior-, fracturas de tobillo, patologías del pie reumatoide, enfermedades neuromusculares y las complicaciones del pie diabético. Recopilación y análisis de datos: Dos autores seleccionaron de forma independiente los resultados de la búsqueda para identificar a aquellos que satisfacen los criterios de inclusión y evaluaron la calidad de los incluidos mediante una lista de control basado en la Evaluación de la Colaboración Cochrane de Riesgo. Esta herramienta se centró en el riesgo de la selección, el rendimiento, la detección, la heterogeneidad y el sesgo de notificación. Resultados. Cuatro ensayos, con 140 sujetos, cumplieron los criterios de inclusión para la revisión. Los cuatro fueron juzgados como de alto riesgo de sesgo en al menos un área, y también estaban en riesgo de sesgo incierto en al menos otra zona. Todos anotaron altamente en relación al sesgo de deserción, debido al corto seguimiento tiempos y diseños experimentales utilizados. Los datos no se agruparon debido al alto nivel de heterogeneidad identificada en las intervenciones evaluadas, los participantes seleccionados y medir los resultados. Los resultados de un estudio sugieren que después de cuatro semanas de uso ortesis puede resultar en una mejora significativa en vaivén lateral medio, y pueden resultar en una mejor, aunque no significativa, en general relacionados con la calidad de vida de los pies (Roma 2004). Un estudio (Redmond 2009) sugiere que su efecto sobre la distribución de la presión plantar en el pie puede no depender de si son personalizados o dispositivos prefabricados. Aunque este estudio se identificaron cambios significativos en algunas variables de presión plantar tanto con la costumbre y dispositivos prefabricados, otro (Esterman 2005) no encontró ningún efecto significativo de longitud ¾ ortesis prefabricadas sobre el dolor, la incidencia de lesiones, salud pie o de calidad de vida en un grupo de reclutas de la fuerza aérea. El cuarto estudio (Jung 2009) sugiere que el ejercicio de los músculos intrínsecos del pie puede mejorar el efecto de las ortesis. A pesar de estos resultados, ya que cada estudio incurrió riesgo de sesgo en al menos un área no se pueden sacar conclusiones

Accelerated apoptosis in SLE neutrophils cultured with anti-dsDNA antibody isolated from SLE patient serum: a pilot study.

Increased numbers of apoptotic neutrophils are found in SLE, related to disease activity and levels of anti-dsDNA antibody. The mechanism of increased apoptosis is not clear, but anti-dsDNA antibody has been shown to induce apoptosis in neutrophils from normal subjects and in certain cell lines. In this study, polyclonal anti-dsDNA antibody was isolated from the serum of a patient with active SLE, and was shown to substantially accelerate apoptosis in neutrophils from SLE patients as compared with neutrophils from healthy control or rheumatoid arthritis subjects.

Hand arthritis in systemic lupus erythematosus: an ultrasound pictorial essay.

A small minority of systemic lupus erythematosus (SLE) patients may develop a deforming arthritis, typically with a non-erosive (Jaccoud's) pattern, although erosive features indistinguishable from rheumatoid arthritis may also occur. High-resolution ultrasonography (HRUS) allows detailed 'real time' imaging of joint and tendon morphostructural changes involving the hand in patients with several rheumatic diseases. The main aim of this pictorial essay is to provide the first descriptive HRUS and power Doppler (PD) findings of joint and tendon involvement of the hand and wrist in patients with SLE arthritis. Seventeen patients with SLE and hand involvement were examined. HRUS of the wrist, 2nd and 3rd MCP joints, 3rd PIP joint and 2nd, 3rd and 4th finger flexor tendons were studied in the dominant hand for each patient. Sixteen (94%) patients had joint effusion or synovial hypertrophy in the wrist. Twelve (71%) patients had joint effusion or synovial hypertrophy in 2nd or 3rd MCPJs. Eight (47%) patients had erosion at 2nd or 3rd MCPJs. In three cases erosions were not present radiologically. Eleven (65%) patients had evidence of tenosynovitis. In SLE, HRUS with PD detects a high prevalence of inflammatory pathology in the tendons and synovium of the hand and wrist, and a high prevalence of MCP joint erosions. HRUS offers a sensitive, real-time and readily repeatable assessment of soft-tissue, inflammatory and bony changes in SLE hands.

Distinctive effects of G-CSF, GM-CSF and TNFalpha on neutrophil apoptosis in systemic lupus erythematosus.

OBJECTIVE: To investigate the influence of culture with G-CSF GM-CSF and TNFalpha on neutrophil apoptosis, comparing neutrophils from SLE patients with rheumatoid arthritis (RA) patients and healthy control subjects. METHODS: Neutrophils were isolated from SLE (n= 10), RA (n= 10) and healthy control subjects (n= 10), and cultured with two different concentrations of G-CSF, GM-CSF and TNFalpha. Proportion of apoptotic neutrophils at T=0, T=2hrs and T=24hrs was measured using FITC-labelled annexinV and flow cytometry. RESULTS: Significantly more neutrophils were apoptotic at T=0 in the SLE subjects than in the other groups (median, range--Control 3.5% (0.3-7.9) SLE 9.5% (2.9-29.1) RA 3.0% (0.4-23.0) p

The CTLA4 + 49A/G and CT60 polymorphisms and chronic inflammatory arthropathies in Northern Ireland

Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with an autoimmune background. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) protein plays a key role in the down-regulation of T cell activation. We analyzed the CTLA4 +49A/G and CT60 polymorphisms in cohorts of Northern Irish RA and JIA patients and healthy control subjects using restriction fragment length polymorphism methods. The +49 A allele was increased in RA (61.2%; P=0.02; OR=1.28; 95% C.I.=1.04-1.58) and JIA (61.8%; P=0.14) patients compared to the control population (55.3%). No significant association was observed for the CT60 polymorphism. Haplotype analysis revealed a significantly different distribution of +49 A/G-CT60 haplotypes in RA and JIA patients compared to controls (P value

Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women.

Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with polygenic autoimmune background. We analysed the IL-4 +33 C/T and IL-4R Q551R single nucleotide polymorphisms (SNPs) in 294 RA, 72 JIA and 165 controls from Northern Ireland. Analysis of the individual phenotypes (RA or JIA) showed that both the IL-4 +33 TT (P = 0.02; OR: 0.25, 95% CI: 0.07-0.87) and the IL-4R Q551R CC genotypes (P = 0.001; OR: 0.19, 95% CI: 0.06-0.56) were exclusively decreased in female RA patients compared to female controls. Similar non-significant trends were observed in female JIA patients (OR: 0.25, 95% CI: 0.03-2.11 and OR: 0.31, 95% CI: 0.07-1.47, respectively). Analysis of the common phenotype (inflammatory arthropathy; i.e. JIA and RA combined) corroborated the unique association of these polymorphisms with female inflammatory arthropathy (P = 0.013 and 0.002, respectively). This is the first demonstration of sex-specific association of the two foremost genes of the IL-4 signalling cascade with chronic inflammatory arthropathies.

Dipeptidyl peptidase IV (DPP IV) and related molecules in type 2 diabetes

Dipeptidyl peptidase IV (DPP IV) is a widely distributed physiological enzyme that can be found solubilized in blood, or membrane-anchored in tissues. DPP IV and related dipeptidase enzymes cleave a wide range of physiological peptides and have been associated with several disease processes including Crohn's disease, chronic liver disease, osteoporosis, multiple sclerosis, eating disorders, rheumatoid arthritis, cancer, and of direct relevance to this review, type 2 diabetes. Here, we place particular emphasis on two peptide substrates of DPP IV with insulin-releasing and antidiabetic actions namely, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The rationale for inhibiting DPP IV activity in type 2 diabetes is that it decreases peptide cleavage and thereby enhances endogenous incretin hormone activity. A multitude of novel DPP IV inhibitor compounds have now been developed and tested. Here we examine the information available on DPP IV and related enzymes, review recent preclinical and clinical data for DPP IV inhibitors, and assess their clinical significance.

The human synovial fluid proteome: A key factor in the pathology of joint disease

This review aims to summarise our knowledge to date on the protein complement of the synovial fluid (S F). The tissues, structure and pathophysiology of the synovial joint are briefly described. The salient features of the S F proteome, how it is composed and the influence of arthritic disease are highlighted and discussed. The concentrations of proteins that have been detected and quantified in SF are drawn together from the literature on osteoarthritis, rheumatoid arthritis and juvenile idiopathic arthritis. The measurements are plotted to give a perspective on the dynamic range of protein levels within the SF. Approaches to proteomic analysis of SF to date are discussed along with their findings. From the recent literature reviewed within, it is becoming increasingly clear that analysis of the SF proteome as a whole, could deliver the most valuable differential diagnostic fingerprints of a number of arthritic disorders. Further development of proteomic platforms could characterise prognostic profiles to improve the cliniciads ability to resolve unremitting disease by existing and novel therapeutics.

The emerging relevance of the cysteine protease Cathepsin S in disease

Cathepsin S is a lysosomal cysteine protease that has been shown to play a key role in MHC class II antigen presentation. Consequently, it has been extensively evaluated as a therapeutic target in autoimmune diseases, such as rheumatoid arthritis and psoriasis. Additionally, clinical and mechanistic evidence is emerging, revealing its inappropriate expression and secretion in a wide range of disease states including atherosclerosis and tumourigenesis. This review covers the known role and consequences of cathepsin S activity in these pathological disorders, highlighting various studies that have demonstrated its utility as a therapeutic target. This review also examines challenges that exist towards the development of agents that specifically target this protease and discusses the studies to date that have applied cathepsin S inhibitors in disease models.

FELTYS-SYNDROME TREATED WITH RHG-CSF ASSOCIATED WITH FLARE OF ARTHRITIS AND SKIN RASH

A patient with Felty's syndrome and rheumatoid arthritis was treated with recombinant granulocyte stimulating factor rhG-CSF (Neupogen) in view of severe neutropenia. He had a prompt rise in his neutrophil count and associated with this a severe flare of his arthritis and a skin rash. rhG-CSF was stopped, his neutrophil count fell rapidly and his symptoms resolved. rhG-CSF and the resulting rise in neutrophil count may be associated with flare of autoimmune disease in susceptible individuals.

Lipoxidation products as biomarkers of oxidative damage to proteins during lipid peroxidation reactions

Oxidative stress is implicated in the pathogenesis of numerous disease processes including diabetes mellitus, atherosclerosis, ischaemia reperfusion injury and rheumatoid arthritis. Chemical modification of amino acids in protein during lipid peroxidation results in the formation of lipoxidation products which may serve as indicators of oxidative stress in vivo. The focus of the studies described here was initially to identify chemical modifications of protein derived exclusively from lipids in order to assess the role of lipid peroxidative damage in the pathogenesis of disease. Malondialdehye (MDA) and 4-hydroxynonenal (HNE) are well characterized oxidation products of polyunsaturated fatty acids on low-density lipoprotein (LDL) and adducts of these compounds have been detected by immunological means in atherosclerotic plaque. Thus, we first developed gas chromatography-mass spectrometry assays for the Schiff base adduct of MDA to lysine, the lysine-MDA-lysine diimine cross-link and the Michael addition product of HNE to lysine. Using these assays, we showed that the concentrations of all three compounds increased significantly in LDL during metal-catalysed oxidation in vitro. The concentration of the advanced glycation end-product N epsilon-(carboxymethyl)lysine (CML) also increased during LDL oxidation, while that of its putative carbohydrate precursor the Amadori compound N epsilon-(1-deoxyfructose-1-yl)lysine did not change, demonstrating that CML is a marker of both glycoxidation and lipoxidation reactions. These results suggest that MDA and HNE adducts to lysine residues should serve as biomarkers of lipid modification resulting from lipid peroxidation reactions, while CML may serve as a biomarker of general oxidative stress resulting from both carbohydrate and lipid oxidation reactions.

Felty's syndrome treated with rhG-CSF associated with flare of arthritis and skin rash

A patient with Felty's syndrome and rheumatoid arthritis was treated with recombinant granulocyte stimulating factor rhG-CSF (Neupogen) in view of severe neutropenia. He had a prompt rise in his neutrophil count and associated with this a severe flare of his arthritis and a skin rash. rhG-CSF was stopped, his neutrophil count fell rapidly and his symptoms resolved. rhG-CSF and the resulting rise in neutrophil count may be associated with flare of autoimmune disease in susceptible individuals.

Periodontitis and systemic diseases:A record of discussions of working group 4 of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases

Background There has been an explosion in research into possible associations between periodontitis and various systemic diseases and conditions. Aim To review the evidence for associations between periodontitis and various systemic diseases and conditions, including chronic obstructive pulmonary disease (COPD), pneumonia, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer, and to document headline discussions of the state of each field. Periodontal associations with diabetes, cardiovascular disease and adverse pregnancy outcomes were not discussed by working group 4. Results Working group 4 recognized that the studies performed to date were largely cross-sectional or case-control with few prospective cohort studies and no randomized clinical trials. The best current evidence suggests that periodontitis is characterized by both infection and pro-inflammatory events, which variously manifest within the systemic diseases and disorders discussed. Diseases with at least minimal evidence of an association with periodontitis include COPD, pneumonia, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer. The working group agreed that there is insufficient evidence to date to infer causal relationships with the exception that organisms originating in the oral microbiome can cause lung infections. Conclusions The group was unanimous in their opinion that the reported associations do not imply causality, and establishment of causality will require new studies that fulfil the Bradford Hill or equivalent criteria. Precise and community-agreed case definitions of periodontal disease states must be implemented systematically to enable consistent and clearer interpretations of studies of the relationship to systemic diseases. The members of the working group were unanimous in their opinion that to develop data that best inform clinicians, investigators and the public, studies should focus on robust disease outcomes and avoid surrogate endpoints. It was concluded that because of the relative immaturity of the body of evidence for each of the purported relationships, the field is wide open and the gaps in knowledge are large. © 2013 European Federation of Periodontology and American Academy of Periodontology.

Periodontal systemic associations: review of the evidence

Aim: To critically appraise recent research into associations between periodontal disease and systemic diseases and conditions specifically respiratory disease, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer.

Methods: A MEDLINE literature search of papers published between 2002 and April 2012 was conducted. Studies that included periodontitis as an exposure were identified. Cross-sectional epidemiological investigations on large samples, prospective studies and systematic reviews formed the basis of the narrative review. A threshold set for the identification of periodontitis was used to identify those studies that contributed to the conclusions of the review.

Results: Many of the investigations were cross-sectional secondary analyses of existing data sets in particular the NHANES studies. There were a small number of systematic reviews and prospective studies. There was substantial variability in the definitions of exposure to periodontitis. A small number of studies met the threshold set for periodontitis and supported associations; however, in some of the chronic diseases there were no such studies. There was strong evidence from randomized controlled trials that interventions, which improve oral hygiene have positive effects on the prevention of nosocomial pneumonias.

Conclusions: There was substantial heterogeneity in the definitions used to identify periodontitis and very few studies met a stringent threshold for periodontitis. Published evidence supports modest associations between periodontitis and some, although not all, of the diseases and conditions reviewed. There is a need to reach a consensus on what constitutes periodontitis for future studies of putative associations with systemic diseases.

Abundant genetic overlap between blood lipids and immune-mediated diseases indicates shared molecular genetic mechanisms

Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS) to investigate shared single nucleotide polymorphisms (SNPs) between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals), applying new False Discovery Rate (FDR) methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG), low density lipoproteins (LDL), high density lipoproteins (HDL)] and a selection of archetypal immune-mediated diseases (Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis). We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88), LDL (n = 87) and HDL (n = 52). Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2) and intestinal host-microbe interactions (e.g. ATG16L1). We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents.