Enteral nutrition: a first option for nutritional support of children following allo-SCT?

Parenteral nutrition (PN) is the treatment of choice for nutritional support of patients undergoing allo-SCT following myeloablative conditioning (MAC). Here we prospectively assessed the outcomes of early enteral nutrition (EN) in a paediatric cohort. From 2003 to 2010, all 65 consecutive children undergoing MAC allo-SCT at our referral centre began EN the day after transplantation. Post-transplant and nutritional outcomes of patients receiving only EN (EN group, n=50) were compared with those of patients requiring additional PN (EN-PN group, n=15). In the EN group time to platelet recovery (P=0.01) and length of hospitalisation (P<0.001) were shorter, while in the EN-PN group the proportion of unrelated donors (P=0.02) and the frequency of severe acute GVHD (aGVHD; P=0.004) were higher. All patients were alive at day 100. PN was started 14 days after transplant because of poor digestive tolerance to EN or severe gut aGVHD. The body mass index Z-score in the EN-PN group decreased from transplant to discharge (P=0.02). In only 23% of cases was PN required for severely ill patients. Our results suggest that EN might be considered to be an option for nutritional support in children undergoing MAC allo-SCT, while PN should be used only as a rescue option, possibly in combination with EN.     

Monoclonal B-cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B-cell subsets

Monoclonal B-cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B-cell subsets.Little is known about the distribution of normal lymphoid cells and their subsets in the peripheral blood (PB) of subjects with monoclonal B-cell lymphocytosis (MBL). In our study, we compared the absolute number of PB lymphoid cells and their subpopulations in 95 MBL cases with normal lymphocyte counts vs. 617 age-/sex-matched non-MBL healthy subjects (controls), using highly sensitive flow cytometry. MBL cases showed significantly reduced numbers of normal circulating B-cells, at the expense of immature and naive B-cells; in addition, CD4+CD8+ double-positive T-cells and CD8+ T-cells were significantly lower and higher vs. controls, respectively. Moreover, most normal B-cell subsets were significantly decreased in PB at >1% MBL-counts, vs. "low-count" MBL cases, and lower amounts of immature/naive B-cells were detected in biclonal (particularly in cases with coexisting CLL-like- and non-CLL-like B-cell clones) vs. monoclonal MBL subjects. In summary, our results show imbalanced (reduced) absolute numbers of recently produced normal circulating B-cells (e.g., immature and na?ve B-cells) in MBL, which becomes more pronounced as the MBL cell count increases.     

Phase I trial of a novel human monoclonal antibody mAb216 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia

Background

This phase I trial was conducted to determine the safety and pharmacokinetics of monoclonal antibody 216, a human monoclonal Immunoglobulin M antibody targeting a linear B-cell lactosamine antigen, administered alone and in combination with vincristine in patients with relapsed or refractory B-cell acute lymphoblastic leukemia, and to preliminarily assess tumor targeting and efficacy.

Design and Methods

Three cohorts of patients received escalating doses of monoclonal antibody 216 administered as an intravenous infusion. In the case of poor response to the first dose of monoclonal antibody 216 alone, defined as less than 75% reduction in peripheral blood blast count, a second dose of the antibody with vincristine was given between days 4 and 7. Responses were assessed weekly until day 35. Serum concentration of monoclonal antibody 216 was measured before and after infusion. Monoclonal antibody 216 targeting was determined with an anti-idiotypic antibody to monoclonal antibody 216 and preliminary efficacy was analyzed by changes in peripheral blood blasts.

Results

Thirteen patients were enrolled. One episode of grade 3 epistaxis was the only dose-limiting toxicity observed. All patients showed a poor response to the first monoclonal antibody 216 infusion with a decrease in peripheral blasts from 6–65% in 9 patients. In 8 patients, addition of vincristine to monoclonal antibody 216 resulted in an average reduction of the peripheral blasts of 81%. One patient without peripheral blasts achieved a hypoplastic marrow without evidence of leukemia after one infusion of monoclonal antibody 216 and monoclonal antibody 216/vincristine each. Monoclonal antibody 216 was detected on peripheral blasts in all patients.

Conclusions

Treatment with monoclonal antibody 216 in combination with vincristine is feasible and well tolerated in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Binding of monoclonal antibody 216 to leukemic blasts was efficient, and favorable early responses were observed.     

Self-regulatory practices of drivers with Parkinson's disease: Accuracy of patient reports

BackgroundStudies suggest that drivers with Parkinson's disease (PD) are more likely than controls to restrict their exposure and avoid challenging situations possibly to compensate for declining abilities; however it is questionable whether patient reports should be taken at face value. To address this issue, this study examined agreement between self-reported and actual driving practices in drivers with and without PD.MethodsTwo electronic devices (one with GPS) were installed in the vehicles of 26 drivers with PD (mean age 71.5 ± 6.8, 77% men) and 20 controls (mean age 70.6 ± 7.9, 80% men) for two weeks. Participants completed a questionnaire on usual driving patterns, scales on Situational Driving Frequency (SDF) and Avoidance (SDA), the MoCA and an interview.ResultsSelf-estimates of distance driven (km) over the two weeks were inaccurate in both groups; however the tendency to under-estimate was more pronounced in PD drivers. Drivers with PD reported more self-restrictions (higher SDA scores, p < .01; lower SDF scores, p < .05), yet drove more at night, in bad weather, in rush hour and on highways than they reported. Drivers with PD had significantly lower MoCA scores overall (p < .01) and on the memory subtest (p < .05), however, MoCA scores were not correlated with self-reported restrictions, or actual driving distance in either group.ConclusionsThese findings indicate that patient reports of driving behavior should not be taken at face value by researchers or clinicians. Patients with PD may be more likely than drivers in general to have problems with recall and possibly less awareness of their driving practices.     

Exploring the effectiveness of an Internet-based program for reducing caregiver distress using the iCare Stress Management e-Training Program

Objective: Determine if the online iCare Stress Management e-Training Program reduces stress, bother, depression, and poor life quality for dementia family caregivers (CGs).

Method: CGs (N = 150) were randomly assigned to the iCare Condition (ICC) or to the Education/Information-Only Condition (EOC) for a 3-month period. Change in self-report measures of stress (PSS) (primary outcome), caregiver bother(RMBPC), depression (CES-D), and quality of life (PQOL) (secondary outcomes) was determined, along with usage of new information in one's own caregiving.

Results: A mixed ANOVA revealed that change in perceived stress was significant for the ICC but not the EOC (p = .017). Changes in the other measures were not significant. More caregivers in the ICC used the materials in their own caregiving situation than those in the EOC. Roughly one-third of the caregivers enrolled in the study dropped prior to completion.

Conclusion: Results are promising, but the high dropout is a concern. Future efforts to improve dropout rate and increase participant engagement are warranted. To our knowledge, this is the first attempt to present an evidence-based intervention for CGs via the Internet.     

Auditory temporal envelope processing in a patient with left-hemisphere damage

Abstract

Auditory temporal envelope processing was investigated in a patient showing a mild speech identification impairment following left-hemisphere damage. Three tasks evaluated the patient's ability to: (1) detect a sinusoidal amplitude modulation (SAM) applied to a white noise, as a function of modulation rate (i.e. her ‘temporal modulation transfer function’ or TMTF); (2) discriminate between two white noises amplitude modulated by time-reversed temporally asymmetric envelopes; and (3) identify white noises amplitude modulated by the temporal envelope of speech stimuli. Measurements of intensity discrimination thresholds were performed as a control task. Compared to normal data, the results obtained with the brain-damaged patient showed: (1) increased thresholds for the detection of SAM; (2) increased thresholds for the discrimination of temporal asymmetry; and (3) a deficit in the identification of speechenvelope noise stimuli. In contrast, intensity discrimination thresholds were within the normal range. Taken together, the results indicate a general impairment in auditory temporal acuity, which is now specified as a deficit in the coding of envelope rate and shape, and a deficit in the ability to use temporal envelope cues in speech processing. These results support the hypothesis that left-hemisphere damage is associated with an impairment in time analysis, which may cause, in turn, speech intelligibility disorders.     

Exome sequencing in a family with intellectual disability, early onset spasticity, and cerebellar atrophy detects a novel mutation in EXOSC3

Whole exome sequencing in two-generational kindred from Bangladesh with early onset spasticity, mild intellectual disability, distal amyotrophy, and cerebellar atrophy transmitted as an autosomal recessive trait identified the following two missense mutations in the EXOSC3 gene: a novel p.V80F mutation and a known p.D132A change previously associated with mild variants of pontocerebellar hypoplasia type 1. This study confirms the involvement of RNA processing proteins in disorders with motor neuron and cerebellar degeneration overlapping with spinocerebellar ataxia 36 and rare forms of hereditary spastic paraplegia with cerebellar features.