RESUMO
BACKGROUND: Immediate reactions to ß-lactams are the most common causes of anaphylactic reactions and can be life-threatening. The few known genetic factors influencing these reactions suggest a link with atopy and inflammation. OBJECTIVE: We performed a fine-mapping genome-wide association study of the genetic predictors of ß-lactam allergy to better understand the underlying mechanisms. METHODS: We studied 387 patients with immediate allergic reactions to ß-lactams and 1124 paired control subjects from Spain. We replicated the results in 299 patients and 362 paired control subjects from Italy. RESULTS: We found significant associations with the single nucleotide polymorphisms rs4958427 of ZNF300 (c.64-471G>A, P = 9.9 × 10(-9)), rs17612 of C5 (c.4311A>C [p.Glu1437Asp], P = 7.5 × 10(-7)), rs7754768 and rs9268832 of the HLA-DRA | HLA-DRB5 interregion (P = 1.6 × 10(-6) and 4.9 × 10(-6)), and rs7192 of HLA-DRA (c.724T>G [p.Leu242Val], P = 7.4 × 10(-6)) in an allelic model, with similar results in an additive model. Single nucleotide polymorphisms of HLA-DRA and ZNF300 predicted skin test positivity to amoxicillin and other penicillins but not to cephalosporins. A haplotype block in HLA-DRA and the HLA-DRA | HLA-DRB5 interregion encompassed a motif involved in balanced expression of the α- and ß-chains of MHC class II, whereas rs7192 was predicted to influence α-chain conformation. HLA-DRA rs7192 and rs8084 were significantly associated with allergy to penicillins and amoxicillin (P = 6.0 × 10(-4) and P = 4.0 × 10(-4), respectively) but not to cephalosporins in the replication study. CONCLUSIONS: Gene variants of HLA-DRA and the HLA-DRA | HLA-DRB5 interregion were significant predictors of allergy to penicillins but not to cephalosporins. These data suggest complex gene-environment interactions in which genetic susceptibility of HLA type 2 antigen presentation plays a central role.
Assuntos
Hipersensibilidade a Drogas/genética , Cadeias alfa de HLA-DR/genética , Penicilinas/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/etiologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Itália/epidemiologia , Masculino , Polimorfismo de Nucleotídeo Único , Espanha/epidemiologiaRESUMO
. The complications of enteral nutrition in medical wards. INTRODUCTION: The effects of Enteral Nutrition (EN) in patients unable to feed themselves have been widely explored although studies in low-/mean- intensity words are lacking. AIM: To measure the prevalence of EN side effects in medical wards and to explore their risk factors. Metodi. Observational, retrospective study on matched patients. All patients in the medical departments of the Azienda Ospedaliero-Universitaria Senese were enrolled (81 cases and 162 controls) from 1 August 2018 to 1 September 2019, aged over 50 years and hospitalized for longer than 4 days. The NE side effects such as diarrhea, vomiting, gastric stagnation and abdominal pain were collected from clinical records The presence of EN, age of patients, mobilization and use of antibiotics during hospitalization were considered risk factors. RESULTS: The prevalence of diarrhea, vomiting, gastric and abdominal pain ranged from 4.9% to 11.1%. The EN was not a significant risk factor for the onset of gastrointestinal disorders, and these complications were always lower than in the controls. Vomiting, diarrhea and abdominal pain were more frequently, though not significantly, associated to antibiotic treatments; the age of subjects significantly predicted the diarrhea, showing a protective effect with the age increase. CONCLUSIONS: The study shows a low prevalence of diarrhoea, vomiting and abdominal pain compared to the literature. These symptoms were not significantly associated to the EN, that cannot be considered a risk factor.