The influence of glucocorticoid receptor single nucleotide polymorphisms on outcome after haematopoietic stem cell transplantation

Haematopoietic stem cell transplantation (HSCT) remains the only cure for most haematological malignancies, however, the mortality rate remains high. Complications after HSCT include relapse, graft versus host disease (GvHD), graft rejection and infection. Over the last few years several groups, have demonstrated that non‐HLA gene polymorphisms can be predictive of outcome after HSCT. Since the glucocorticoid cortisol is pivotal in the regulation of the immune system, we decided to examine single nucleotide polymorphisms (SNPs; rs6198, rs33388 and rs33389) within the glucocorticoid receptor (GR) and correlate with HSCT outcome. The training set consisted of patients (n = 458) who underwent HSCT for acute leukaemia between 1983 and 2005. In the recipients, the absence of the ACT haplotype and absence of the T allele of rs33388 were associated with decreased OS and the absence of the ACT haplotype, the absence of the T allele of rs33388 and the presence of the ATA haplotype were associated with increased risk of relapse. In addition, the presence of the ACT haplotype in the recipient showed a trend to be associated with increased risk of chronic graft versus host disease (cGvHD). The patients in this cohort received mainly myeloablative conditioning (n = 327). The SNPs in the glucocorticoid receptor were then investigated in a validation set (n = 251) of HSCT patients transplanted for acute leukaemia from 2006. This cohort contained significantly more patients that had received reduced intensity conditioning (RIC). Some of the results could be validated in these patients. However, contrary to the training set, the absence of the haplotype ACT in the donor in this cohort was associated with increased risk of cGvHD. Differences in the conditioning were shown to influence the results. These results are the first to associate GR SNPs with HSCT outcome and demonstrate the inherent problems of replicating SNP association studies in HSCT, due to different pre‐transplant regimens.     

Arthroscopic treatment of lateral epicondylitis: Indication, technique and early results

The purpose of this study is to present the results of the arthroscopic treatment of lateral epicondylitis. Twenty patients with lateral epicondylitis (mean age 42 years) were treated arthroscopically. The average duration of symptoms prior to surgery was 14 months. The arthroscopic joint inspection showed an intact capsule in seven patients (type-I lesion), in eight patients a linear capsule tear (type-II lesion) and in six patients a complete rupture of the capsule (type-III lesion). An associated intraarticular pathology was documented in eight patients. Within an average follow-up period of 1.8 years, local pain and function were documented and analyzed. Subjective pain at rest was reduced from 5.0 to 0.5 points, pain at daily living activities from 6.0 to 1.0 points and pain at athletic activities from 7.3 to 1.2 points in the VAS score. Function increased from 5.2 to an average value of 10.9 (max. 12 points). Patients returned back to work after 3.2 weeks. In conclusion, the arthroscopic release in patients with radial epicondylitis is a reproducible method with a marked postoperative increase in function within a short rehabilitation period.     

Common infections and the role of burnout in a Dutch working population

OBJECTIVE: To determine if burnout is a risk factor for common cold, flu-like illness and gastroenteritis. METHODS: We conducted a prospective cohort study among 12,140 employees at baseline, using three consecutive self-administered questionnaires. The Maslach Burnout Inventory-General Survey (MBI-GS) was used to define employees with burnout complaints (Level 1) and clinical burnout (Level 2). The cross-sectional relationship between burnout and the occurrence of common infections was assessed at baseline, using logistic regression analysis. Survival analysis with Cox regression was performed to study the longitudinal relationship between burnout and the subscales of the MBI-GS as risk factors for common infections. RESULTS: For both levels of burnout, an increased incidence of common infections was found at baseline. The largest effect was found for the relationship between burnout and gastroenteritis (OR: 1.86, CI: 1.57-2.21 for Level 1 and OR: 3.59, CI: 2.09-6.17 for Level 2). The longitudinal analyses showed comparable results, although less pronounced. The largest effect was again found for gastroenteritis (RR: 1.55, CI: 1.28-1.86 for Level 1 and RR: 2.09, CI: 1.09-3.98 for Level 2). For flu-like illness and common cold, we found smaller but significant effects at Level 1, but not at Level 2. The subscale "Exhaustion" was found to be the strongest predictor for infections at both levels of burnout. CONCLUSIONS: This study provides evidence for burnout as a risk factor for common infections in a large heterogeneous population. Taking into account that burnout or its subscales are not primary etiological agents for these common infections, the observed effects are large.     

Heritability of Smoking Initiation and Nicotine Dependence

In contrast to other aspects of smoking behavior, little attention has been paid to the genetics of nicotine dependence. In this paper, three models (single liability dimension, independent liability dimension and combined model) have been applied to data on smoking initiation and nicotine dependence (n = 1572 Dutch twin pairs, mean age 30.5). A combined model best described the data. This model postulates a smoking initiation dimension and a nicotine dependence dimension, which are not independent. For both males and females, individual differences in smoking initiation were explained by genetic (44%), shared environmental (51%) and unique environmental (5%) influences. The nicotine dependence dimension was influenced only by genetic (75%) and unique environmental (25%) factors. The substantial impact of genetic factors on nicotine dependence emphasizes the need for further research to localize and identify specific genes and pathways involved in nicotine dependence.