Residual disease detected by multidimensional flow cytometry signifies high relapse risk in patients with de novo acute myeloid leukemia: a report from Children's Oncology Group

Early response to induction chemotherapy is a predictor of outcome in acute myeloid leukemia (AML). We determined the prevalence and significance of postinduction residual disease (RD) by multidimensional flow cytometry (MDF) in children treated on Children's Oncology Group AML protocol AAML03P1. Postinduction marrow specimens at the end of induction (EOI) 1 or 2 or at the end of therapy from 249 patients were prospectively evaluated by MDF for RD, and presence of RD was correlated with disease characteristics and clinical outcome. Of the 188 patients in morphologic complete remission at EOI1, 46 (24%) had MDF-detectable disease. Those with and without RD at the EOI1 had a 3-year relapse risk of 60% and 29%, respectively (P < .001); the corresponding relapse-free survival was 30% and 65% (P < .001). Presence of RD at the EOI2 and end of therapy was similarly predictive of poor outcome. RD was detected in 28% of standard-risk patients in complete remission and was highly associated with poor relapse-free survival (P = .008). In a multivariate analysis, including cytogenetic and molecular risk factors, RD was an independent predictor of relapse (P < .001). MDF identifies patients at risk of relapse and poor outcome and can be incorporated into clinical trials for risk-based therapy allocation. This study was registered at www.clinicaltrials.gov as NCT00070174.     

High-throughput molecular diagnosis of von Willebrand disease by next generation sequencing methods

Genetic analysis of von Willebrand disease by von Willebrand factor gene sequencing has not yet become routine practice. Nevertheless, the prospects for molecular diagnosis have changed dramatically in recent years with the unveiling of next-generation sequencing platforms. With the goal of applying this technology to von Willebrand disease, we designed a strategy for von Willebrand factor gene enrichment and multiplexing based on short polymerase chain reactions. Forty patients were simultaneously analyzed enabling the identification of 43 mutations, including 36 substitutions, 2 intronic splice site mutations, 2 indels, and 3 deletions. By pooling patient genomic DNA before polymerase chain reaction enrichment, indexing samples with barcode tags, and re-sequencing on the next-generation sequencing instrument, at least 350 patients and relatives per run can be simultaneously analyzed in a fast, inexpensive manner. This is one of the first reports in which this technology has been shown to be feasible for large-scale mutation screening by single gene re-sequencing.     

Sedentary behavior and physical activity are independently related to functional fitness in older adults

The last decades of life have been traditionally viewed as a time of inevitable disease and frailty. Sedentary living and physical activity may influence capacity to perform activities that are needed to maintain physical independence in daily living. A total of 117 males and 195 females, aged 65–103 years, were assessed for physical activity and sedentary time with accelerometers and for functional fitness with the Senior Fitness Test battery. Based on the individual scores for each fitness item, a Z-score was created. Associations between functional fitness with sedentary time and moderate-to-vigorous physical activity (MVPA) were analyzed. A negative association was found between the composite Z-score for functional fitness and the sedentary time, even adjusting for MVPA and other confounders. On the other hand, MVPA was positively associated with the composite Z-score for functional fitness, independently of the sedentary time. In conclusion elderly who spend more time in physical activity or less time in sedentary behaviors exhibit improved functional fitness and other confounders. The results reinforce the importance of promoting both the reduction of sedentary behaviors and the increase of MVPA in this age group, as it may interfere at older ages in order to preserve functional fitness and performance of daily functioning tasks.     

Niobium pentoxide as a novel filler for dental adhesive resin

Objectives

The purpose of this study was to develop an adhesive resin with incorporation of niobium pentoxide and evaluate its properties.

Methods

Niobium pentoxide was characterised by X-ray diffraction, surface area, particle size, micro-Raman, scanning electron microscopy and the effectiveness of silanisation process by Fourier Transform Infrared (FTIR). An experimental adhesive resin was formulated with 0, 5, 10 and 20 wt% Nb₂O₅. The formulated adhesive resins were evaluated based on microhardness, degree of conversion, radiopacity and interface (resin/dentine) characterisation by micro-Raman.

Results

The particles used in this study presented a monoclinic crystalline phase with typical chemical groups and micrometre mean size. Microhardness and radiopacity increased with higher amounts of Nb₂O₅, and the particles were able to penetrate into the hybrid layers.

Conclusions

Therefore, Nb₂O₅ may be an alternative for polymer-based biomaterials.Clinical significance: Niobium pentoxide could be used to produce adhesive resins with enhanced properties.