Salvage Therapy after Allogeneic Hematopoietic Cell Transplantation: Targeted and Low-Intensity Treatment Options in Myelodysplastic Syndrome and Acute Myeloid Leukemia

Patients with high-risk myeloid neoplasms, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), are offered allogeneic hematopoietic cell transplantation (alloHCT) to improve the likelihood of long-term disease control. More than 50% of patients with high-risk disease will relapse after HCT and face a poor prognosis with shortened survival. The recent development of targeted therapies and effective, low-intensity treatment strategies will likely improve the outcomes of these patients. In MDS, hypomethylating agents (HMAs) are the mainstay of salvage therapy but new treatments with APR-246 and luspatercept demonstrate excellent results in phase 1 and phase 3 clinical studies, respectively. In AML, new directed agents in the relapsed/refractory setting include gilteritinib (FLT3-ITD/-TKD), ivosidenib (IDH1), and enasidenib (IDH2). In patients without targetable mutations, HMAs may be used, and early data with venetoclax-based regimens are encouraging

Affect and Mindfulness as Predictors of Change in Mood Disturbance, Stress Symptoms, and Quality of Life in a Community-Based Yoga Program for Cancer Survivors

Little attention has been paid to the psychological determinants by which benefits are accrued via yoga practice in cancer-related clinical settings. Using a longitudinal multilevel modeling approach, associations between affect, mindfulness, and patient-reported mental health outcomes, including mood disturbance, stress symptoms, and health-related quality of life (HRQL), were examined in an existing seven-week yoga program for cancer survivors. Participants (N=66) were assessed before and after the yoga program and at three- and six-month follow-ups. Decreases in mood disturbance and stress symptoms and improvements in HRQL were observed upon program completion. Improvements in mood disturbance and stress symptoms were maintained at the three- and six-month follow-ups. HRQL exhibited further improvement at the three-month follow-up, which was maintained at the six-month follow-up. Improvements in measures of well-being were predicted by initial positive yoga beliefs and concurrently assessed affective and mindfulness predictor variables. Previous yoga experience, affect, mindfulness, and HRQL were related to yoga practice maintenance over the course of the study

Schoolwide Application of Positive Behavior Support in an Urban High School:. Journal Of Positive Behavior Interventions

Abstract: The nuances of the application of schoolwide positive behavior supports (PBS) in an urban high school setting were investigated. Impact of implementation was measured using qualitative interviews and observations, including the School-wide Evaluation Tool (SET), Effective Behavior Support Survey, Student Climate Survey, and office disciplinary referrals. The results indicated that schoolwide PBS was implemented in an urban high school setting with some success. The overall level of implementation of PBS reached 80% as measured by the SET. Staff and teachers increased their level of perceived priority for implementing PBS in their school. A decrease in monthly discipline referrals to the office and the proportion of students who required secondary and tertiary supports was noted. These findings seem to indicate that PBS may be an important process for improving outcomes for teachers and students in urban high school settings

Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy.

MotivationMultiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia.ResultsWe performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified.Availability and implementationDatasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/.Supplementary informationSupplementary data are available at Bioinformatics online

GateFinder: projection-based gating strategy optimization for flow and mass cytometry

Motivation: High-parameter single-cell technologies can reveal novel cell populations of interest, but studying or validating these populations using lower-parameter methods remains challenging.Results: Here, we present GateFinder, an algorithm that enriches high-dimensional cell types with simple, stepwise polygon gates requiring only two markers at a time. A series of case studies of complex cell types illustrates how simplified enrichment strategies can enable more efficient assays, reveal novel biomarkers and clarify underlying biology

A randomised controlled trial to evaluate the efficacy of a 6 month dietary and physical activity intervention for prostate cancer patients receiving androgen deprivation therapy

<p>Abstract</p> <p>Background</p> <p>Treatment with Androgen Deprivation Therapy (ADT) for prostate cancer is associated with changes in body composition including increased fat and decreased lean mass; increased fatigue, and a reduction in quality of life. No study to date has evaluated the effect of dietary and physical activity modification on the side-effects related to ADT. The aim of this study is to evaluate the efficacy of a 6-month dietary and physical activity intervention for prostate cancer survivors receiving ADT to minimise the changes in body composition, fatigue and quality of life, typically associated with ADT.</p> <p>Methods</p> <p>Men are recruited to this study if their treatment plan is to receive ADT for at least 6 months. Men who are randomised to the intervention arm receive a home-based tailored intervention to meet the following guidelines a) ≥ 5 servings vegetables and fruits/day; b) 30%-35% of total energy from fat, and < 10% energy from saturated fat/day; c) 10% of energy from polyunsaturated fat/day; d) limited consumption of processed meats; e) 25-35 gm of fibre/day; f) alcoholic drinks ≤ 28 units/week; g) limited intake of foods high in salt and/or sugar. They are also encouraged to include at least 30 minutes of brisk walking, 5 or more days per week. The primary outcomes are change in body composition, fatigue and quality of life scores. Secondary outcomes include dietary intake, physical activity and perceived stress. Baseline information collected includes: socio-economic status, treatment duration, perceived social support and health status, family history of cancer, co-morbidities, medication and supplement use, barriers to change, and readiness to change their health behaviour. Data for the primary and secondary outcomes will be collected at baseline, 3 and 6 months from 47 intervention and 47 control patients.</p> <p>Discussion</p> <p>The results of this study will provide detailed information on diet and physical activity levels in prostate cancer patients treated with ADT and will test the feasibility and efficacy of a diet and physical activity intervention which could provide essential information to develop guidelines for prostate cancer patients to minimise the side effects related to ADT.</p> <p>Trial registration</p> <p>ISRCTN trial number ISCRTN75282423</p

Systemic Immunologic Consequences of Chronic Periodontitis

Chronic periodontitis (ChP) is a prevalent inflammatory disease affecting 46% of the US population. ChP produces a profound local inflammatory response to dysbiotic oral microbiota that leads to destruction of alveolar bone and tooth loss. ChP is also associated with systemic illnesses, including cardiovascular diseases, malignancies, and adverse pregnancy outcomes. However, the mechanisms underlying these adverse health outcomes are poorly understood. In this prospective cohort study, we used a highly multiplex mass cytometry immunoassay to perform an in-depth analysis of the systemic consequences of ChP in patients before (n = 28) and after (n = 16) periodontal treatment. A high-dimensional analysis of intracellular signaling networks revealed immune system–wide dysfunctions differentiating patients with ChP from healthy controls. Notably, we observed exaggerated proinflammatory responses to Porphyromonas gingivalis–derived lipopolysaccharide in circulating neutrophils and monocytes from patients with ChP. Simultaneously, natural killer cell responses to inflammatory cytokines were attenuated. Importantly, the immune alterations associated with ChP were no longer detectable 3 wk after periodontal treatment. Our findings demarcate systemic and cell-specific immune dysfunctions in patients with ChP, which can be temporarily reversed by the local treatment of ChP. Future studies in larger cohorts are needed to test the boundaries of generalizability of our results

Adherence to yoga and exercise interventions in a 6-month clinical trial

<p>Abstract</p> <p>Background</p> <p>To determine factors that predict adherence to a mind-body intervention in a randomized trial.</p> <p>Design</p> <p>We analyzed adherence data from a 3-arm trial involving 135 generally healthy seniors 65–85 years of age randomized to a 6-month intervention consisting of: an Iyengar yoga class with home practice, an exercise class with home practice, or a wait-list control group. Outcome measures included cognitive function, mood, fatigue, anxiety, health-related quality of life, and physical measures. Adherence to the intervention was obtained by class attendance and biweekly home practice logs.</p> <p>Results</p> <p>The drop-out rate was 13%. Among the completers of the two active interventions, average yoga class attendance was 77% and home practice occurred 64% of all days. Average exercise class attendance was 69% and home exercise occurred 54% of all days. There were no clear effects of adherence on the significant study outcomes (quality of life and physical measures). Class attendance was significantly correlated with baseline measures of depression, fatigue, and physical components of health-related quality of life. Significant differences in baseline measures were also found between study completers and drop-outs in the active interventions. Adherence was not related to age, gender, or education level.</p> <p>Conclusion</p> <p>Healthy seniors have good attendance at classes with a physically active intervention. Home practice takes place over half of the time. Decreased adherence to a potentially beneficial intervention has the potential to decrease the effect of the intervention in a clinical trial because subjects who might sustain the greatest benefit will receive a lower dose of the intervention and subjects with higher adherence rates may be functioning closer to maximum ability before the intervention. Strategies to maximize adherence among subjects at greater risk for low adherence will be important for future trials, especially complementary treatments requiring greater effort than simple pill-taking.</p