Brain volume changes in hyposmic patients before and after olfactory training.

OBJECTIVES/HYPOTHESIS: Olfactory dysfunction is thought to be associated with reduced gray matter (GM) volume in olfactory-related brain areas. The aim of this study was to determine GM structural changes within olfactory-related regions of the brain in patients with smell loss due to upper respiratory tract infection (URTI) before and after olfactory rehabilitation. STUDY DESIGN: Prospective intervention case-control study. METHODS: Magnetic resonance imaging structural brain images were collected from 30 patients with smell loss due to URTI and 31 controls. Patients exposed themselves to odors (olfactory training [OT]) over 12 weeks and then were rescanned. Olfactory testing was performed using the validated Sniffin' Sticks test. GM was investigated with voxel-based morphometry. RESULTS: GM volumes were found to be reduced in the limbic system and thalamus among pretraining patients compared to controls; in patients, OT was associated with a significant increase of GM volume in these two regions. The GM volume within other olfactory-related regions was not different between patients and controls. In addition, no relevant difference between the GM volume pre- and post-OT was observed in primary olfactory-related regions. CONCLUSIONS: OT was associated with an increase in GM volume of the hippocampus and the thalamus, possibly pointing toward a strategy for more effective exploitation of olfactory signals based on a higher degree of attention toward odors and association of memories with olfactory input. LEVEL OF EVIDENCE: 3b. Laryngoscope, 128:1531-1536, 2018.

Wilms tumor gene single nucleotide polymorphism rs16754 predicts a favorable outcome in children with acute lymphoblastic leukemia.

PURPOSE: Wilms tumor gene single nucleotide polymorphism (WT1 SNP) rs16754 has been described as a favorable risk marker in patients with acute myeloid leukemia. Subsequent studies revealed inconsistent results in both adult and pediatric patients. We analyzed its impact on clinical outcome in children with acute lymphoblastic leukemia (ALL) for the first time. METHODS: WT1 SNP rs16754 of 158 children with ALL treated according to ALL Berlin-Frankfurt-Münster treatment trials from 1990 to 2009 and 43 hematopoietic stem cell donors was analyzed by allelic discrimination. WT1 SNP status was correlated with disease characteristics and clinical outcome comparing SNP (WT1(GG/AG)) and wildtype (WT1(AA)). RESULTS: At least one minor allele was found in 23.4 % of patients and 34.9 % of donors (P = 0.07). Distribution of patient and disease characteristics was similar between WT1(GG/AG) and WT1(AA). In multivariate analyses, WT1 SNP was an independent good prognostic marker for cumulative incidence of relapse (CIR WT1(AA) vs. WT1(GG/AG) HR = 3.384, P = 0.021) and event-free survival (EFS; event risk WT1(AA) vs. WT1(GG/AG) HR = 2.503, P = 0.036). Univariate subanalyses of patients who underwent an allogeneic hematopoietic stem cell transplantation revealed more significant differences in CIR (P = 0.017), EFS (P = 0.012), and overall survival (OS; P = 0.017). Donor's WT1 SNP status did not affect outcome. We found no correlation between WT1 SNP and WT1 expression level at diagnosis (P = 0.634). CONCLUSION: WT1 SNP rs16754 predicts improved CIR and EFS. Outcome differences were more prominent in transplanted children. Our findings identify WT1 SNP rs16754 as a favorable risk marker in pediatric ALL which is independent from known risk factors.