Riisevalentine1702
The role of decentralized assessment of measurable residual disease (MRD) for risk stratification in acute myeloid leukemia (AML) remains largely unknown, and so it does which methodological aspects are critical to empower the evaluation of MRD with prognostic significance, particularly if using multiparameter flow cytometry (MFC). We analyzed 1076 AML patients in first remission after induction chemotherapy, in whom MRD was evaluated by MFC in local laboratories of 60 Hospitals participating in the PETHEMA registry. We also conducted a survey on technical aspects of MRD testing to determine the impact of methodological heterogeneity in the prognostic value of MFC. Our results confirmed the recommended cutoff of 0.1% to discriminate patients with significantly different cumulative-incidence of relapse (-CIR- HR0.71, P less then 0.001) and overall survival (HR 0.73, P = 0.001), but uncovered the limited prognostic value of MFC based MRD in multivariate and recursive partitioning models including other clinical, genetic and treatment related factors. Virtually all aspects related with methodological, interpretation, and reporting of MFC based MRD testing impacted in its ability to discriminate patients with different CIR. Thus, this study demonstrated that "real-world" assessment of MRD using MFC is prognostic in patients at first remission, and urges greater standardization for improved risk-stratification toward clinical decisions in AML.Despite significant progress over the last few decades in the treatment of acute myeloid leukemia (AML), there still remains a major unmet medical need for this disease. Immunotherapy approaches for redirecting pan CD3+ T cells to target leukemia blasts have shown limited efficacy in clinical trials and often accompanied with severe toxicity in AML patients. We designed an alternative engager molecule (Anti-TRGV9/anti-CD123), a bispecific antibody that can simultaneously bind to the Vγ9 chain of the Vγ9Vδ2+ γδ T cell receptor and to AML target antigen, CD123, to selectively recruit Vγ9+ γδ T cells rather than pan T cells to target AML blasts. Our results suggest that prototypic bispecific antibodies (a) selectively activate Vγ9+ γδ T cells as judged by CD69 and CD25 surface expression, and intracellular Granzyme B expression, (b) selectively recruit Vγ9+ γδ T cells into cell-cell conjugate formation of γδ T cells with tumor cells indicating selective and effective engagement of effector and target tumor cells, and (c) mediate γδ T cell cytotoxicity (in vitro and in vivo) against tumor antigen-expressing cells. Collectively, these findings suggest that selectively redirecting Vγ9+ γδ T cells to target AML blasts has a potential for immunotherapy for AML patients and favors further exploration of this concept.
Weight loss (WL) and subsequent regain are complex physiologic processes, and our understanding of the hormonal changes associated with these processes continues to evolve. We aimed to examine the effects of behavioral WL on 6-month changes in ghrelin and GLP-1 and evaluate the effects of these changes in gut hormones on weight regain among older adults.
One hundred seventy-seven obese (BMI 33.5 (3.5) kg/m
) older adults (66.9 ± 4.7 years, 71.2% female, 67.6% white) were randomized to WL (WL; n = 68), WL plus aerobic training (n = 79), or WL plus resistance training (n = 75) for 18 months. Ghrelin, GLP-1, power of food scale (PFS), and weight were measured at baseline, 6 months, and 18 months.
There was no differential treatment effect on change in either gut hormone, however, there was a significant time effect across all groups (p < 0.001), with increases in ghrelin (∆ = +106.77 pg/ml; 95% CI = + 84.82, +128.71) and decreases in GLP-1 (∆ = -4.90 pM; 95% CI = -6.27, -3.51) at 6-month. Ratings on the PFS decreased from baseline to 6-month and there was significant loss of weight from baseline to either 6- or 18-month, ∆ = -7.96 kg; 95% CI = -7.95, -8.78 and ∆ = -7.80 kg; 95% CI = -8.93, -6.65, respectively (p < 0.001). Changes in ghrelin and GLP-1 at 6-month did not predict weight regain from 6- to 18-month.
Among older adults with obesity and cardiometabolic disease, the intensive phase of dietary WL results in increasing levels of ghrelin and decreasing levels of GLP-1 that are unrelated to weight regain a year later. Registered with ClinicalTrials.gov (NCT01547182).
Among older adults with obesity and cardiometabolic disease, the intensive phase of dietary WL results in increasing levels of ghrelin and decreasing levels of GLP-1 that are unrelated to weight regain a year later. Registered with ClinicalTrials.gov (NCT01547182).
Childhood overweight and obesity are a global concern, with prevalence rising dramatically over the last decades. The condition is caused by an increase in energy intake and reduction of physical activity, leading to excessive fat accumulation, followed by systemic chronic inflammation and altered function of immune cell responses. This study aimed at providing new insights regarding sex-specificity on the inflammatory response to obesity in the young patient.
Forty-three Brazilian obese adolescents (Female = 22 and Male=21, BMI (body mass index) Z-score average = 2.78 ± 0.51) and forty-nine eutrophic adolescents (Female = 24 and Male = 25, BMI Z-score average = -0.35 ± 0.88) were enrolled in the study. Anthropometrical analyses and blood cell counts were carried out. Using Luminex®xMAP™ technology, circulating serum cytokines, chemokines, and inflammatory biomarkers were analyzed. Two-way ANOVA test, Tukey's test, and Spearman's correlation coefficient were employed, with a significance threshold set at sex dimorphism in the inflammatory profile of obese adolescents.
Our data support a complex relationship between adiposity, blood cell count, and circulating inflammatory cytokine content. High SAA levels suggest that this factor may play a critical role in local and systemic inflammation. In the eutrophic group, females presented a lower status of inflammation, as compared to males. Both obese boys and girls showed an increased inflammatory response in relation to eutrophic counterparts. Taken together, results point out to clear sex dimorphism in the inflammatory profile of obese adolescents.
To assess the relationships between daily sedentary time (ST), prolonged ST, moderate-to-vigorous physical activity (MVPA), and behavioral and neuroelectric indices of cognitive control in adults with overweight and obesity (OW/OB).
A cross-sectional design was used. Overall, 89 adults (BMI = 31.9 ± 4.9 kg/m
) provided measures of ST, prolonged ST (i.e., ST accumulated in ≥20 min), and MVPA from a hip-worn accelerometer worn over 7 days. Inhibitory control was measured with a modified Eriksen flanker task and cognitive flexibility with task switching. The amplitude and the latency of the P3 component of event-related potentials during each task were used as measures of attentional resource allocation and information processing speed, respectively.
After adjusting for ST and MVPA, prolonged ST was related to greater interference (i.e., a larger decrement in accuracy between congruent and incongruent trials of the flanker task) indicative of a specific relationship between prolonged ST and poorer inhibitory control. Before adjusting for ST, MVPA was related to a smaller Global Switch Cost expressed as larger (more positive) amplitude of the P3 difference wave (mixed-task minus single-task condition of the switch task). Adjustment for ST attenuated this association to non-significance.
Our findings suggest that future interventions focused on improving inhibitory control in adults with OW/OB should target restructuring ST in addition to current efforts to increase MVPA.
Our findings suggest that future interventions focused on improving inhibitory control in adults with OW/OB should target restructuring ST in addition to current efforts to increase MVPA.
Muscle function is a marker of current and prospective health/independence throughout life. The effects of sex and obesity (OB) on the loss of muscle function in ageing remain unresolved, with important implications for the diagnosis/monitoring of sarcopenia. To characterise in vivo knee extensors' function, we compared muscles torque and power with isometric and isokinetic tests in older men (M) and women (W), with normal range (NW) of body mass index (BMI) and OB.
In 70 sedentary older M and W (69 ± 5 years), NW and OB (i.e. BMI < 30 kg m
and ≥30 kg m
, respectively) we tested the right knee's extensor (i) isometric torque at 30°, 60°, 75° and 90° knee angles, and (ii) isokinetic concentric torque at 60, 90, 150, 180 and 210° s
angular speeds. Maximal isometric T-angle, maximal isokinetic knee-extensor torque-velocity, theoretical maximal shortening velocity, maximal power, optimal torque and velocity were determined in absolute units, normalised by body mass (BM) and right leg lean mass (LLM
)cle function and muscle contractile quality is conserved in individuals with class I OB, muscle function normalised for BM, which defines the ability to perform independently and safely the activities of daily living, is impaired in comparison with physiological ageing.
Health-related quality of life (HRQoL) in age-related macular degeneration (AMD) is difficult to estimate as most generic tools underestimate vision. Our aim was to measure the effect of AMD on generic and visual quality of life and how it relates to handicap. ABSK 091 We also aimed to validate the NG82 NICE AMD classification. Finally, we studied if a bolt-on visual domain increased the EQ-5D sensitivity to AMD.
Ninety-six patients with AMD participated in this observational cross-sectional study. Visual (VF-14) and generic questionnaires (EQ-5D) with VIS, and the London handicap scale (LHS) was used to quantify HRQoL and handicap. ANOVA and regression analysis were used to identify significant associations.
Visual dysfunction in AMD has a significant effect in VF-14 (P < 0.001), LHS (p < 0.001), and EQ-5D (p = 0.015). The EQ-5D was less sensitive than the VF-14 and LHS and was not significantly correlated with the VIS bolt-on domain (p = 0.608). On the other hand, VIS was significantly associated with visual acuity (p < 0.001), AMD diagnosis (p = 0.005), VF-14 (p < 0.001), and LHS (p < 0.001). The new AMD classification was a good predictor of visual HRQoL and had an excellent association with visual acuity in the best eye.
This article shows that visual impairment is associated with lower HRQoL and with an increased handicap. It also suggests that a visual dimension may increase the EQ-5D sensitivity in AMD. There was a relationship between visual impairment and handicap with the items of the new NICE AMD classification, which supports its use.
This article shows that visual impairment is associated with lower HRQoL and with an increased handicap. It also suggests that a visual dimension may increase the EQ-5D sensitivity in AMD. There was a relationship between visual impairment and handicap with the items of the new NICE AMD classification, which supports its use.
