RESUMEN
BACKGROUND: Blood plasma collected at time of surgery is an excellent source of patient material for investigations into disease aetiology and for the discovery of novel biomarkers. Previous studies on limited sets of proteins and patients have indicated that pre-operative fasting and anaesthesia can affect protein levels, but this has not been investigated on a larger scale. These effects could produce erroneous results in case-control studies if samples are not carefully matched. METHODS: The proximity extension assay (PEA) was used to characterize 983 unique proteins in a total of 327 patients diagnosed with ovarian cancer and 50 age-matched healthy women. The samples were collected either at time of initial diagnosis or before surgery under general anaesthesia. RESULTS: 421 of the investigated proteins (42.8%) showed statistically significant differences in plasma abundance levels comparing samples collected at time of diagnosis or just before surgery under anaesthesia. CONCLUSIONS: The abundance levels of the plasma proteome in samples collected before incision, i.e., after short-time fasting and under general anaesthesia differs greatly from levels in samples from awake patients. This emphasizes the need for careful matching of the pre-analytical conditions of samples collected from controls to cases at time of surgery in the discovery as well as clinical use of protein biomarkers.
RESUMEN
OBJECTIVE: To study the impact of genetic and lifestyle factors on protein biomarkers and develop personally normalized plasma protein profiles (PNPPP) controlling for non-disease-related variance. MATERIALS AND METHODS: Proximity extension assays were used to measure 145 proteins in 632 controls and 344 cases with non-communicable diseases. RESULTS: Genetic and lifestyle factors explained 20-88% of the variation in healthy controls. Adjusting for these factors reduced the number of candidate biomarkers by 63%. CONCLUSION: PNPPP efficiently controls for non-disease-related variance, allowing both for efficient discovery of novel biomarkers and for covariate-independent linear cut-offs suitable for clinical use.
Asunto(s)
Biomarcadores/sangre , Proteínas Sanguíneas/análisis , Enfermedades Cardiovasculares/sangre , Neoplasias/sangre , Anciano , Análisis de Varianza , Proteínas Sanguíneas/genética , Índice de Masa Corporal , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/genética , Enfermedad/clasificación , Enfermedad/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo/métodos , Estudio de Asociación del Genoma Completo/estadística & datos numéricos , Genotipo , Humanos , Inflamación/sangre , Inflamación/diagnóstico , Inflamación/genética , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Neoplasias/genética , Polimorfismo de Nucleótido Simple , Proteoma/análisis , Proteoma/genética , FumarRESUMEN
BACKGROUND: Treatment of palmar hyperhidrosis with botulinum toxin (BTX) requires effective anesthesia, but previous methods have not provided enough pain relief or have resulted in a prolonged impaired hand function. OBJECTIVE: This is a study of bilateral forearm intravenous regional anesthesia using prilocaine for BTX treatment of palmar hyperhidrosis. METHODS: In all, 166 patients (100 female and 66 male) were treated bilaterally with intracutaneous BTX type A injections using intravenous regional anesthesia with prilocaine (5 mg/mL). In a subgroup of patients, forearm nerves were studied with neurophysiologic methods and blood concentrations of prilocaine were measured. Pain evaluation with a visual analog scale was accompanied with a questionnaire about the treatment. RESULTS: In all, 95% of the patients answering the questionnaire (response rate 89%) were satisfied with the anesthetic effect. No serious adverse events occurred. There was a fast recovery of motor function (in median 6 minutes) and sensory function (in median 20 minutes). No subclinical signs of sensory nerve damage were found. LIMITATIONS: Recall and reporting bias are potential sources of limitations in this study. CONCLUSION: Bilateral forearm intravenous regional anesthesia provides an effective and well-tolerated anesthesia during BTX treatment of palmar hyperhidrosis.