RESUMO
BACKGROUND: Crohn's disease is one of the two categories of inflammatory bowel diseases that affect the gastrointestinal tract. The heritability estimate has been reported to be 0.75. Several genes linked to Crohn's disease risk have been identified using a plethora of strategies such as linkage-based studies, candidate gene association studies, and lately through genome-wide association studies (GWAS). Nevertheless, to our knowledge, a compendium of all the genes that have been associated with CD is lacking. METHODS: We conducted functional analyses of a gene set generated from a systematic review where genes potentially related to CD found in the literature were analyzed and classified depending on the genetic evidence reported and putative biological function. For this, we retrieved and analyzed 2496 abstracts comprising 1067 human genes plus 22 publications regarding 133 genes from GWAS Catalog. Then, each gene was curated and categorized according to the type of evidence associated with Crohn's disease. RESULTS: We identified 126 genes associated with Crohn's disease risk by specific experiments. Additionally, 71 genes were recognized associated through GWAS alone, 18 to treatment response, 41 to disease complications, and 81 to related diseases. Bioinformatic analysis of the 126 genes supports their importance in Crohn's disease and highlights genes associated with specific aspects such as symptoms, drugs, and comorbidities. Importantly, most genes were not included in commercial genetic panels suggesting that Crohn's disease is genetically underdiagnosed. CONCLUSIONS: We identified a total of 126 genes from PubMed and 71 from GWAS that showed evidence of association to diagnosis, 18 to treatment response, and 41 to disease complications in Crohn's disease. This prioritized gene catalog can be explored at http://victortrevino.bioinformatics.mx/CrohnDisease .
Assuntos
Doença de Crohn , Doenças Inflamatórias Intestinais , Biologia Computacional , Doença de Crohn/diagnóstico , Estudo de Associação Genômica Ampla , HumanosRESUMO
OBJECTIVES: Our study aimed to identify the prevalence and severity of gastrointestinal (GI) symptoms and dysphagia in patients with amyotrophic lateral sclerosis (ALS) and to assess whether a correlation exists between these symptoms and the severity of ALS progression. METHODS: The presence and severity of GI symptoms and dysphagia were identified by means of the Gastrointestinal Symptom Rating Scale (GSRS) and the Functional Outcome Swallowing Scale (FOSS). The Revised ALS Functional Rating Scale (ALSFRS-R) was utilized to determine the severity of ALS. Analysis of data was performed with Spearman correlations in semi-qualitative variables of clinical scales. ALSFRS-R scores were divided into 2 categories: those with mild to moderate ALS (≥40-30 points) and patients with moderate to advanced ALS (29-≤20 points). RESULTS: We studied 43 patients with definite ALS. The most frequent GI symptoms were constipation (60.5%), rectal tenesmus (57.5%), hard stools (55.0%), and borborygmus (42.5%). The moderate to advanced ALS stage was correlated with constipation (r = 0.334; p = 0.028), acid regurgitation (r = 0.384; p = 0.013), eructation (r = 0.334; p = 0.032), rectal tenesmus (r = 0.498; p = 0.001), and functional dysphagia (r = 0.656; p = <0.001). CONCLUSIONS: Early detection of these GI symptoms can guide timely therapeutic decisions to avoid weight loss, a predictor for worse prognosis. This study highlights the relevance of the detection of these symptoms in ALS patients who score ≤29 points in the ALSFRS-R scale to establish an appropriate treatment, prevent systemic complications, provide more comfort, and improve quality of life.
Assuntos
Esclerose Lateral Amiotrófica , Transtornos de Deglutição , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/epidemiologia , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Progressão da Doença , Humanos , Prevalência , Qualidade de Vida , Índice de Gravidade de DoençaRESUMO
Despite the worldwide increasing incidence and prevalence of Inflammatory Bowel Disease (IBD), our knowledge about it in Mexico is still limited. The aim of this study is to describe the incidence and prevalence of IBD as well as its clinical and socio-demographical characteristics in Mexico from a nation-wide perspective.Multicenter nation-wide cohort study that included 42 IBD clinics from all over the country that participated with electronically register of the new cases over 17 years as well as all known existing cases together with their clinical and socio-demographical characteristics from patients with IBD (ulcerative colitis [UC], Crohn disease [CD], and inflammatory bowel disease unclassified [IBDU]). The data collection was conducted between January and October 2017. Incidence, prevalence, and mean incidence over 2 decades were then calculated. Data base was analyzed using SPSS v24 program SPSS (version 24, IBM Corp., Armonk, NY, USA).A total of 2645 patients with IBD were registered. The crude incidence rates of IBD, UC, and CD, respectively, were 0.21, 0.16, and 0.04 cases per 100,000-person year. The highest incidence was registered in the year 2015, compared with to the previous years. The mean incidence of IBD has increased steadily from 0.05 to 0.21 per 100,000 person-years over the past 15 years (Pâ=â.06). The incidence of IBD new cases have increased significantly throughout the last 16 years, 5.9-fold for IBD, 5.3-fold for UC, and 9.5-fold for CD. The prevalence rates of IBD, UC, and CD, respectively, were 1.83, 1.45, and 0.34 cases per 100,000-person-year.This is the first study from a nation-wide perspective that demonstrated a significant increase of prevalence and incidence of IBD in Mexico in the last 15 years.
Assuntos
Previsões , Doenças Inflamatórias Intestinais/epidemiologia , Vigilância da População , Adolescente , Adulto , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Incidência , Masculino , México/epidemiologia , Prevalência , Estudos Retrospectivos , Adulto JovemRESUMO
Biologics are increasingly being used to modify the course of immune-mediated inflammatory diseases. Some main agents are monoclonal antibodies and a fusion-protein that target TNF. This group includes adalimumab, infliximab, certolizumab pegol, golimumab and etanercept. Although the efficacy of anti-TNFs is supported by numerous randomized clinical trials, their pharmacokinetics depend on many factors, in particular immunogenicity, which can cause marked and rapid clearance and a consequent decrease in efficacy. Kinetics involve receptors that recognize the Fc fragment of the antibody and are responsible for various processes. Pharmacological advances permit optimizing the pharmacokinetics of anti-TNFs. In this review, we examine the kinetics of anti-TNF biologics, and consequent therapeutic implications, and overview some latest developments in the field. First draftsubmitted: 17 May 2016; Accepted for publication: 15 September2016; Published online: 14 October 2016.
Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Produtos Biológicos/uso terapêutico , Doenças do Sistema Imunitário/terapia , Imunoterapia/métodos , Inflamação/terapia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Ensaios Clínicos como Assunto , Humanos , Doenças do Sistema Imunitário/imunologia , Inflamação/imunologiaRESUMO
Herein, we describe the isolation of Staphylococcus pasteuri, Staphylococcus pettenkoferi and Staphylococcus gallinarum and summarize the clinical characteristics of five patients. Cases were identified over a 2-year surveillance period that identified the respective strains using microbiologic and molecular methods. These data suggest that rare coagulase-negative staphylococcal infections may be under-diagnosed due to difficulties associated with routine clinical laboratory diagnostic methods.
Assuntos
Coagulase/metabolismo , Hospedeiro Imunocomprometido , Infecções Estafilocócicas/microbiologia , Staphylococcus/enzimologia , Staphylococcus/isolamento & purificação , Adolescente , Demografia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fenótipo , Análise de Sequência de DNA , Staphylococcus/genéticaRESUMO
BACKGROUND: The incidence of coagulase-negative staphylococci reported as causative agents of nosocomial infections has risen in the last decade. The aim of this study was to characterize biofilm formation, antibiotic resistance, SCCmec type, and genetic relatedness in clinical isolates of Staphylococcus cohnii, Staphylococcus hominis, and Staphylococcus sciuri recovered from humans. METHODS: Clinically relevant isolates of S. cohnii (n = 15), S. hominis (n = 9), and S. sciuri (n = 6), were collected from patients. Biofilm formation was evaluated using crystal violet staining, drug susceptibility was assessed using the broth microdilution method, and methicillin resistance was measured using the cefoxitin disk test. SCCmec was typed using 2 different methodologies, and genetic relatedness was determined by pulsed-field gel electrophoresis (PFGE). RESULTS: Sixty percent (9/15) of S. cohnii, 33% (3/9) of S. hominis, and 50% (3/6) of S. sciuri isolates were categorized as weak producers of biofilm. None of the isolates were resistant to vancomycin or linezolid. All 3 species showed a high resistance (> 66%) to ampicillin, levofloxacin, erythromycin, and ceftriaxone, and the majority of the isolates were methicillin-resistant. PFGE revealed that the S. cohnii isolates comprised 1 dominant clone. CONCLUSIONS: The S. cohnii, S. hominis, and S. sciuri isolates analyzed in this study showed a high methicillin resistance and resistance to other antimicrobials. The results of this study strongly suggest that coagulase-negative staphylococci harbour new SCCmec elements. We report the first case of a clone of S. cohnii associated with human disease.
Assuntos
Infecções Estafilocócicas/microbiologia , Staphylococcus/classificação , Staphylococcus/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Biofilmes/crescimento & desenvolvimento , Criança , Análise por Conglomerados , Impressões Digitais de DNA , Farmacorresistência Bacteriana , Eletroforese em Gel de Campo Pulsado , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem Molecular , Staphylococcus/isolamento & purificação , Staphylococcus/fisiologia , Adulto JovemRESUMO
OBJECTIVES: Mexicans have an increased rate of alcohol abuse and alcoholic liver disease. Factors influencing the severity of alcoholic hepatitis (AH) in Mexicans are unknown. The aims of the present study were to identify the prognostic factors of short-term mortality in Mexican patients with AH and to validate the existing prognostic models. METHODS: One hundred seventy-five consecutive patients with AH were recruited from four hospital centers in Mexico. Demographic, clinical, and biochemical parameters were obtained at admission. Univariate and multivariate logistic regression analyses were used for the identification of prognostic factors. The accuracy of different models was evaluated by their area under the receiver operating characteristic (AUROC) curve and comparative risk analysis was performed using the Kaplan-Meier method. RESULTS: Age, serum creatinine, serum bilirubin, leukocyte count, and alcohol consumption >120 g/day were independently associated with short-term mortality. The impact of alcohol consumption was significant among patients with severe AH (48 vs. 72% risk of death, P=0.03). The AUROC (95% confidence interval) curves for the different scores were Maddrey's discriminant function 0.79 (0.72-0.86); model for end-stage liver disease (MELD) 0.83 (0.75-0.89); Glasgow AH score 0.77 (0.70-0.84); and age-bilirubin-international normalized ratio-creatinine (ABIC) score 0.82 (0.75-0.88). The ABIC score allowed an accurate stratification into three different risk subgroups with 13%, 50%, and 81% mortality rate at 90 days (P<0.001). CONCLUSIONS: The amount of alcohol consumption has a negative impact on short-term mortality among Mexicans with AH. The ABIC score is useful and comparable with MELD score for the prognostic stratification of these patients.