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Despite screening programmes, numerous clinical studies and new breast imaging techniques, breast cancer incidence for women continues to rise. The arrival of predictive and personalized medicine could clearly redefine our screening recommendations. One promising approach to improving screening would be to use tools to predict the risk of developing breast cancer, including polygenic risk scores (PRS). This approach will enable us to offer women risk-based screening by adapting the frequency, type and age of screening. This article reviews some definitions of the PRS and breast cancer screening. We also explain the risk assessment models that have been developed and the various studies underway on personalized screening.
Malgré les programmes de dépistage, les nombreuses études cliniques et les nouvelles techniques d'imagerie mammaire, l'incidence du cancer du sein chez la femme continue à augmenter. L'arrivée de la médecine prédictive et personnalisée pourrait clairement redéfinir nos recommandations de dépistage. Une des approches prometteuses pour améliorer le dépistage serait d'utiliser les outils de prédiction du risque de développer un cancer du sein en incluant les scores de risques polygéniques (PRS). Cette approche permettra de proposer aux femmes un dépistage basé sur le risque en adaptant la fréquence des examens ainsi que le type et l'âge du début du dépistage. Cet article reprend quelques définitions concernant le PRS et le dépistage du cancer sein. Nous allons passer en revue les modèles de prédiction de risque qui ont été développés et les différentes études en cours sur le dépistage personnalisé.
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Neoplasias da Mama , Detecção Precoce de Câncer , Medicina Preventiva , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Feminino , Detecção Precoce de Câncer/métodos , Medição de Risco , Medicina Preventiva/métodos , Herança Multifatorial , Predisposição Genética para Doença , Estratificação de Risco GenéticoRESUMO
Hypophosphatasia is a rare genetic disease characterized by abnormal alkaline phosphatase activity and deficiency of bone and teeth mineralization. Hypophosphatasia is well known in pediatrics with typical presentations in children, but mild forms can also be present in adults and are difficult to detect. We present the case of a 50-year-old woman referred for pain management, with a previous diagnosis of fibromyalgia. The association of clinical features (diffuse pain syndrome, early dental loosening, personal history of two fractures with osteoporosis, and family history of osteoporosis) with radiographic (heterotopic calcifications of the yellow and interspinous lumbar ligaments) and biological (low levels of total alkaline phosphatase) indices was suggestive of hypophosphatasia, which was confirmed by genetic analysis. We review and discuss the association between hypophosphatasia, musculoskeletal pain, and calcium pyrophosphate deposition and the importance of raising the diagnosis of adult-onset hypophosphatasia when facing these two rheumatologic entities.
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The Ehlers Danlos syndromes (EDS) are a heterogenous group of inherited connective tissue disorders characterized by generalized joint hypermobility and instability, tissue fragility and multiple functional disorders. The EDS hypermobility type (hEDS) is the most common but the mildest subtype of EDS and is defined by joint involvement. hSED diagnosis is based on clinical criteria because no genetic factors nor molecular basis have yet been identified. Since chronic pain constitutes one of hESD main symptoms, the diagnosis is frequently suspected although the syndrome is rare, with a prevalence estimated to be 1/10.000. An expert clinical evaluation is therefore necessary in order to establish an accurate diagnosis. This allows the implementation of physical therapy which is the only treatment that has proven efficacious in reducing joint instability, generalized pain and secondary osteoarthritis.
Les syndromes d'Ehlers Danlos (SED) sont un groupe hétérogène de maladies héréditaires du tissu conjonctif, caractérisées par une hypermobilité et une instabilité articulaires généralisées, une fragilité des tissus et de multiples troubles fonctionnels. La forme hypermobile du SED (hSED) est le sous-type le plus fréquent, mais le moins sévère des SED. Elle se présente essentiellement sous forme de manifestations articulaires. Le diagnostic du hSED repose sur des critères cliniques, aucun facteur génétique ni base moléculaire n'ayant été identifiés à ce jour. La douleur chronique étant l'un des symptômes principaux du hSED, le diagnostic est souvent évoqué alors que le syndrome est rare, la prévalence étant estimée à 1/10.000. Une expertise clinique est nécessaire afin d'établir un diagnostic correct. Ceci permet la mise en route d'une rééducation kinésithérapique, seul traitement ayant démontré son efficacité pour contrôler les symptômes et réduire l'instabilité articulaire et l'arthrose secondaire.
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Doenças do Tecido Conjuntivo , Síndrome de Ehlers-Danlos , Instabilidade Articular , Anormalidades da Pele , Humanos , Doenças Raras/complicações , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/terapia , Síndrome de Ehlers-Danlos/complicações , Doenças do Tecido Conjuntivo/complicações , Anormalidades da Pele/complicações , Dor/complicações , Instabilidade Articular/diagnóstico , Instabilidade Articular/terapia , Instabilidade Articular/complicaçõesRESUMO
Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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Transtornos da Alimentação e da Ingestão de Alimentos/genética , Transtornos Relacionados ao Uso de Substâncias/genética , Alcoolismo/genética , Transtorno Depressivo Maior/genética , Estudo de Associação Genômica Ampla , Humanos , Desequilíbrio de Ligação , Fenótipo , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Esquizofrenia/genética , Tabagismo/genéticaRESUMO
Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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Anorexia Nervosa/etiologia , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genômica/métodos , Transtornos Mentais/complicações , Doenças Metabólicas/complicações , Locos de Características Quantitativas , Adulto , Anorexia Nervosa/genética , Anorexia Nervosa/patologia , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Transtornos Mentais/genética , Doenças Metabólicas/genética , Fenótipo , PrognósticoRESUMO
GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by â¼9720 regulatory modules, of which â¼3000 operate in multiple tissues and â¼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
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Doenças Inflamatórias Intestinais/genética , Herança Multifatorial , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Doença de Crohn/genética , Feminino , Perfilação da Expressão Gênica , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Análise de Sequência de DNARESUMO
Inflammatory bowel diseases are chronic gastrointestinal inflammatory disorders that affect millions of people worldwide. Genome-wide association studies have identified 200 inflammatory bowel disease-associated loci, but few have been conclusively resolved to specific functional variants. Here we report fine-mapping of 94 inflammatory bowel disease loci using high-density genotyping in 67,852 individuals. We pinpoint 18 associations to a single causal variant with greater than 95% certainty, and an additional 27 associations to a single variant with greater than 50% certainty. These 45 variants are significantly enriched for protein-coding changes (n = 13), direct disruption of transcription-factor binding sites (n = 3), and tissue-specific epigenetic marks (n = 10), with the last category showing enrichment in specific immune cells among associations stronger in Crohn's disease and in gut mucosa among associations stronger in ulcerative colitis. The results of this study suggest that high-resolution fine-mapping in large samples can convert many discoveries from genome-wide association studies into statistically convincing causal variants, providing a powerful substrate for experimental elucidation of disease mechanisms.
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Predisposição Genética para Doença/genética , Variação Genética/genética , Doenças Inflamatórias Intestinais/genética , Locos de Características Quantitativas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sítios de Ligação , Cromatina/genética , Colite Ulcerativa/genética , Doença de Crohn/genética , Epigênese Genética/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Proteína Smad3/genética , Fatores de Transcrição/metabolismo , Adulto JovemRESUMO
OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA. METHODS: We performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes. RESULTS: The major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes. CONCLUSIONS: The lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways.
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Artrite Juvenil/genética , Cromossomos Humanos Par 1/genética , Complexo Principal de Histocompatibilidade/genética , Artrite Juvenil/tratamento farmacológico , Estudos de Casos e Controles , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata. The strongest sJIA-associated SNP, rs151043342 [P = 2.8 × 10(-17), odds ratio (OR) 2.6 (2.1, 3.3)], was part of a cluster of 482 sJIA-associated SNPs that spanned a 400-kb region and included the class II HLA region. Conditional analysis controlling for the effect of rs151043342 found that rs12722051 independently influenced sJIA risk [P = 1.0 × 10(-5), OR 0.7 (0.6, 0.8)]. Meta-analysis of imputed classic HLA-type associations in six study populations of Western European ancestry revealed that HLA-DRB1*11 and its defining amino acid residue, glutamate 58, were strongly associated with sJIA [P = 2.7 × 10(-16), OR 2.3 (1.9, 2.8)], as was the HLA-DRB1*11-HLA-DQA1*05-HLA-DQB1*03 haplotype [6.4 × 10(-17), OR 2.3 (1.9, 2.9)]. By examining the MHC locus in the largest collection of sJIA patients assembled to date, this study solidifies the relationship between the class II HLA region and sJIA, implicating adaptive immune molecules in the pathogenesis of sJIA.
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Artrite Juvenil/genética , Predisposição Genética para Doença/genética , Cadeias HLA-DRB1/genética , Antígenos de Histocompatibilidade Classe II/genética , Polimorfismo de Nucleotídeo Único , Criança , Frequência do Gene , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Metanálise como Assunto , Razão de Chances , Fatores de RiscoRESUMO
In the past decade, the view on genomic structural variation (SV) has been changed completely. SVs, previously considered rare events, are now recognized as the largest source of interindividual genetic variation affecting more bases than single nucleotide polymorphisms, variable number of tandem repeats and other small genetic variants. They have also been shown to play a role in phenotypic variation and in disease. In this review, the authors will provide an introduction to SV; a short historical perspective on the research of this source of genomic variation; a description of the types of structural variants, and on how they may have arisen; and an overview on methods of detecting structural variants, focusing on the analysis of high-throughput sequencing data.
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Genoma Humano , Variação Estrutural do Genoma/genética , Genômica/história , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , História do Século XX , História do Século XXI , HumanosAssuntos
Antirreumáticos/efeitos adversos , Terapia Biológica/efeitos adversos , Predisposição Genética para Doença , Doenças Reumáticas/tratamento farmacológico , Dermatopatias/induzido quimicamente , Dermatopatias/genética , Adulto , Antirreumáticos/uso terapêutico , Proteínas Ricas em Prolina do Estrato Córneo/genética , Feminino , Marcadores Genéticos , Antígenos HLA/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doenças Reumáticas/genéticaRESUMO
Fibromyalgia (FM) is a highly disabling syndrome defined by a low pain threshold and a permanent state of pain. The mechanisms explaining this complex disorder remain unclear, and its genetic factors have not yet been identified. With the aim of elucidating FM genetic susceptibility factors, we selected 313 FM cases having low comorbidities, and we genotyped them on the Illumina 1 million duo array. Genotypic data from 220 control women (Illumina 610k array) was obtained for genome-wide association scan (GWAS) analysis. Copy number variants in FM susceptibility were analyzed by array comparative genomic hybridization (aCGH) experiments on pooled samples using the Agilent 2×400K platform. No single nucleotide polymorphism (SNP) reached GWAS association threshold, but 21 of the most associated SNPs were chosen for replication in 952 cases and 644 controls. Four of the SNPs selected for replication showed a nominal association in the joint analysis, and rs11127292 (MYT1L) was found to be associated to FM with low comorbidities (P=4.28×10(-5), odds ratio [95% confidence interval]=0.58 [0.44-0.75]). aCGH detected 5 differentially hybridized regions. They were followed up, and an intronic deletion in NRXN3 was demonstrated to be associated to female cases of FM with low levels of comorbidities (P=.021, odds ratio [95% confidence interval]=1.46 [1.05-2.04]). Both GWAS and aCGH results point to a role for the central nervous system in FM genetic susceptibility. If the proposed FM candidate genes were further validated in replication studies, this would highlight a neurocognitive involvement in agreement with latest reports.
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Sistema Nervoso Central/fisiologia , Variações do Número de Cópias de DNA/genética , Fibromialgia/diagnóstico , Fibromialgia/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único/genética , Sistema Nervoso Central/patologia , Análise por Conglomerados , Estudos de Coortes , Feminino , HumanosRESUMO
INTRODUCTION: Fibromyalgia (FM) is mainly characterized by widespread pain and multiple accompanying symptoms, which hinder FM assessment and management. In order to reduce FM heterogeneity we classified clinical data into simplified dimensions that were used to define FM subgroups. MATERIAL AND METHODS: 48 variables were evaluated in 1,446 Spanish FM cases fulfilling 1990 ACR FM criteria. A partitioning analysis was performed to find groups of variables similar to each other. Similarities between variables were identified and the variables were grouped into dimensions. This was performed in a subset of 559 patients, and cross-validated in the remaining 887 patients. For each sample and dimension, a composite index was obtained based on the weights of the variables included in the dimension. Finally, a clustering procedure was applied to the indexes, resulting in FM subgroups. RESULTS: VARIABLES CLUSTERED INTO THREE INDEPENDENT DIMENSIONS: "symptomatology", "comorbidities" and "clinical scales". Only the two first dimensions were considered for the construction of FM subgroups. Resulting scores classified FM samples into three subgroups: low symptomatology and comorbidities (Cluster 1), high symptomatology and comorbidities (Cluster 2), and high symptomatology but low comorbidities (Cluster 3), showing differences in measures of disease severity. CONCLUSIONS: We have identified three subgroups of FM samples in a large cohort of FM by clustering clinical data. Our analysis stresses the importance of family and personal history of FM comorbidities. Also, the resulting patient clusters could indicate different forms of the disease, relevant to future research, and might have an impact on clinical assessment.
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Fibromialgia/classificação , Fibromialgia/epidemiologia , Análise de Variância , Análise por Conglomerados , Comorbidade , Humanos , Espanha/epidemiologiaRESUMO
Fibromyalgia is a chronic condition characterized by widespread pain, fatigue, non-restorative sleep and cognitive difficulties that affects 2-4% of the general population. Recently a possible relationship between the FMR1 premutation and fibromyalgia has been pointed out. In attempt to gather more data we screened for the FMR1 CGG expansion 700 DNA samples from unrelated fibromyalgia patients. This data might be useful for evaluating the incorporation of this test in rheumatologic procedures for women with fibromyalgia. The observed frequency of FMR1 premutation carriers (3 of 700, 0.4%) is not significantly different from the estimated rate in the general female population (1/250-1/400) (P=0.539, P=0.716). Clinical examination of the FMR1 premutation carriers identified revealed that all of them had important neurological symptoms with regard to muscular symptoms, neurocognitive alterations and neurovegetative impairments. With regard to other clinical aspects of the disease the cases apparently did not differ from the average fibromyalgia patients. On the basis of our results an FMR1 screening among fibromyalgia female patients would not be recommended. However it would be worthwhile to further evaluate the different clinical presentations that fibromyalgia patients might present based on their FMR1 premutation carrier status.
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Alelos , Fibromialgia/genética , Proteína do X Frágil da Deficiência Intelectual/genética , Mutação , Adulto , Feminino , Fibromialgia/patologia , Fibromialgia/fisiopatologia , Testes Genéticos , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: The LCE3C_LCE3B-del variant is associated with psoriasis and rheumatoid arthritis. Its role in psoriatic arthritis (PsA) is unclear, however, as shown by 3 recent studies with contradictory results. In order to investigate whether LCE3C_LCE3B-del constitutes a risk factor for PsA susceptibility, we first tested this variant in patients with PsA from Spanish and Italian populations and then performed a meta-analysis including the previous case-control studies. METHODS: We genotyped LCE3C_LCE3B-del and its tag single-nucleotide polymorphism (SNP), rs4112788, in an original discovery cohort of 424 Italian patients with PsA and 450 unaffected control subjects. A Spanish replication cohort consisting of 225 patients with PsA and 469 control subjects was also genotyped. A meta-analysis considering 7,758 control subjects and 2,325 patients with PsA was also performed. RESULTS: We observed a significant association between PsA and the LCE3C_LCE3B-del tag SNP in the Italian and Spanish cohorts, with an overall corrected P value of 0.00019 and a corresponding odds ratio of 1.35 (95% confidence interval 1.14-1.59). Stratified analyses by subphenotype indicated a stronger association for patients with oligoarticular disease. Meta-analysis including data from all previous published studies confirmed an association of PsA with the LCE3C_LCE3B-del tag SNP. CONCLUSION: LCE3C_LCE3B-del is a susceptibility factor for PsA, confirming the existence of a shared risk factor involving the epidermal skin barrier in autoimmune disorders.
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Artrite Psoriásica/genética , Proteínas Ricas em Prolina do Estrato Córneo/genética , Predisposição Genética para Doença , Adulto , Alelos , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Espanha , População Branca/genéticaRESUMO
OBJECTIVE: The risk of rheumatoid arthritis (RA) is increased in the offspring of individuals affected with various autoimmune disorders, including psoriasis. Recently, the deletion of 2 genes from the late cornified envelope (LCE) gene cluster, LCE3C and LCE3B, has been associated with psoriasis in several populations. The purpose of this study was to assess whether this polymorphic gene deletion could also be involved in susceptibility to RA. METHODS: We tested for association between the LCE3C_LCE3B copy number variant and a single-nucleotide polymorphism in strong linkage disequilibrium with this variant (rs4112788) and RA in 2 independent case-control data sets (197 and 400 samples from patients with RA, respectively, and 411 and 567 samples from control subjects, respectively), collected at 4 Spanish hospitals. All samples were directly typed for presence of the LCE3C_LCE3B deletion (LCE3C_LCE3B-del) by polymerase chain reaction, and association analysis was performed using the SNPassoc R package. RESULTS: An association of homozygosity for the LCE3C_LCE3B-del and rs4112788 C allele with the risk of RA was observed in the first data set and was replicated in an independent case-control set. A combined analysis showed an overall P value of 0.0012 (odds ratio [OR] 1.45, 95% confidence interval [95% CI] 1.16-1.81) for association of the LCE3C_LCE3B-del. When the analysis was stratified for serologic data, we observed association in anti-cyclic citrullinated peptide (anti-CCP)-positive patients (P = 0.012, OR 1.51 [95% CI 1.09-2.13]) but not in anti-CCP-negative patients. CONCLUSION: We have identified an association between the LCE3C_LCE3B-del and RA, and we have verified a pleiotropic effect of a common genetic risk factor (LCE3C_LCE3B-del) for autoimmune diseases that is involved in both psoriasis and RA.
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Artrite Reumatoide/epidemiologia , Artrite Reumatoide/genética , Proteínas Ricas em Prolina do Estrato Córneo/genética , Deleção de Genes , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/epidemiologia , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Psoríase/epidemiologia , Psoríase/genética , Fatores de RiscoRESUMO
PURPOSE: To evaluate the risk factors of new fractures after vertebroplasty (VP). PATIENTS AND METHOD: Prospective, non-randomized study including patients with acute osteoporotic fractures treated with VP. Baseline visit included clinical and densitometric data. At 30, 90 and 180 days, changes in clinical data and side effects (cement leakage and new fractures) were recorded. To establish the predictive factors of a new fracture, differences between the group of patients with new fractures (R1) and those without fractures (R0) were evaluated. RESULTS: Vertebroplasty was performed in 43 patients (82 vertebrae). Cement leakage into a disc appeared in 11 cases (11,5%) and 12 new fractures occurred in 9 patients. No statistical differences were detected between groups R1 and R0 in the following variables: sex, age, vitamin D levels, T-score, kyphosis angle, primary/secondary osteoporosis, preexisting fractures, number of treated vertebrae and amount of cement injected. A positive, statistical significant correlation, was established between cement leakage into a disk and incidence of adjacent new fractures (p<0.001). CONCLUSIONS: Cement leakage into a disc increases the risk of adjacent new fractures after vertebroplasty.
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Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Vertebroplastia/efeitos adversos , Idoso , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de RiscoAssuntos
Infecções por Bactérias Gram-Positivas , Osteoartrite/microbiologia , Propionibacterium acnes , Adulto , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Masculino , Osteoartrite/diagnóstico , Osteoartrite/tratamento farmacológicoRESUMO
BACKGROUND AND OBJECTIVE: To evaluate the analgesic efficacy and safety of gabapentin in the treatment of carpal tunnel syndrome (CTS), as well as the electromyographic (EMG) evolution after 6 months. PATIENTS AND METHOD: A prospective study with a 6-month follow-up of patients with EMG diagnosis of primary CTS starting treatment with 1.800 mg/day of gabapentin. At baseline visit and after 6 months of treatment a complete clinical evaluation and an EMG study were performed. Adverse effects of gabapentin were also registered. RESULTS: Twenty-five patients were included, mean age (standard deviation) 58.88 (7.69) years. After 6 months of treatment, a statistically significant reduction of pain (p = 0.001) and improvement of severity of symptoms (p = 0.008) were observed, although functional capacity did not change. EMG was performed in 19 patients at 6 months. Compared to baseline EMG: 52.6% patients showed no changes in EMG findings, while 5.3% patients showed improvement and in 26.3% the EMG was normal. Progression was only seen in 15.8% of patients after 6 months of treatment. In 28% of the patients gabapentin was stopped because of side effects. CONCLUSIONS: In our series, gabapentin was effective in the reduction of pain and improvement of the severity of the symptoms. Results of EMG after 6 months of treatment showed no changes, with improvement and/or remission in 84.2% of the cases. The drug was safe and well tolerated.
Assuntos
Aminas/uso terapêutico , Analgésicos/uso terapêutico , Síndrome do Túnel Carpal/tratamento farmacológico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Ácido gama-Aminobutírico/uso terapêutico , Eletromiografia , Feminino , Gabapentina , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Vertebral osteonecrosis is characterized by the presence of the intravertebral vacuum phenomenon. It is a relatively uncommon disease and although it may be caused by different pathologies, the most frequent cause is posttraumatic. The explanation for the presence of intravertebral gas is not known completely. We present the case of a 74-year-old patient who after suffering a vertebral traumatism, to complain of intense vertebral pain. A simple radiological study, CT scan, and magnetic resonance confirmed the presence of intravertebral vacuum phenomenon. We studied this radiological sign and then commented on its evolution after percutaneous vertebroplasty.