The 'omics of obesity in B-cell acute lymphoblastic leukemia.

The obesity pandemic currently affects more than 70 million Americans and more than 650 million individuals worldwide. In addition to increasing susceptibility to pathogenic infections (eg, SARS-CoV-2), obesity promotes the development of many cancer subtypes and increases mortality rates in most cases. We and others have demonstrated that, in the context of B-cell acute lymphoblastic leukemia (B-ALL), adipocytes promote multidrug chemoresistance. Furthermore, others have demonstrated that B-ALL cells exposed to the adipocyte secretome alter their metabolic states to circumvent chemotherapy-mediated cytotoxicity. To better understand how adipocytes impact the function of human B-ALL cells, we used a multi-omic RNA-sequencing (single-cell and bulk transcriptomic) and mass spectroscopy (metabolomic and proteomic) approaches to define adipocyte-induced changes in normal and malignant B cells. These analyses revealed that the adipocyte secretome directly modulates programs in human B-ALL cells associated with metabolism, protection from oxidative stress, increased survival, B-cell development, and drivers of chemoresistance. Single-cell RNA sequencing analysis of mice on low- and high-fat diets revealed that obesity suppresses an immunologically active B-cell subpopulation and that the loss of this transcriptomic signature in patients with B-ALL is associated with poor survival outcomes. Analyses of sera and plasma samples from healthy donors and those with B-ALL revealed that obesity is associated with higher circulating levels of immunoglobulin-associated proteins, which support observations in obese mice of altered immunological homeostasis. In all, our multi-omics approach increases our understanding of pathways that may promote chemoresistance in human B-ALL and highlight a novel B-cell-specific signature in patients associated with survival outcomes.

Protective and Non-Protective Factors of Mental Health Distress in the United States during the COVID-19 Pandemic: A Systematic Review.

Background and objectives: Health care organizations continue to respond to the COVID-19 global pandemic and an ongoing array of related mental health concerns. These pandemic-related challenges continue to be experienced by both the U.S. population and those abroad. Materials and methods: This systematic review queried three research databases to identify applicable studies related to protective and non-protective factors of mental health distress experienced during the pandemic within the United States. Results: Three primary factors were identified as protective factors, potentially helping to moderate the incidence of mental distress during the pandemic: demographics, personal support/self-care resources, and income/financial concerns. Researchers also identified these same three constructs of non-protective factors of mental health distress, as well as two additional variables: health/social status and general knowledge/government mistrust. Conclusions: This systematic review has identified protective and non-protective factors of mental health distress experienced in the United States during the COVID-19 pandemic (to date) that can further assist medical providers in the U.S. and beyond as the pandemic and related mental health concerns continue at a global level.

Outpatient Telehealth Implementation in the United States during the COVID-19 Global Pandemic: A Systematic Review.

Background and objectives: Ambulatory (outpatient) health care organizations continue to respond to the COVID-19 global pandemic using an array of initiatives to provide a continuity of care and related patient outcomes. Telehealth has quickly become an advantageous tool in assisting outpatient providers in this challenge, which has also come with an adaptation of U.S. government policy, procedures, and, as a result, organizational protocols surrounding the delivery of telehealth care. Materials and methods: This systematic review identified three primary facilitators to the implementation and establishment of telehealth services for the outpatient segment of the United States health care industry: patient engagement, operational workflow and organizational readiness, and regulatory changes surrounding reimbursement parity for telehealth care. Results: Researchers identified three barriers impacting the implementation and use of telehealth resources: patient telehealth limitations, lack of clinical care telehealth guidelines, and training, technology, and financial considerations. Conclusions: This systematic review's identified facilitators and barriers for telehealth implementation initiatives in the United States can assist future outpatient providers as the global pandemic and associated public health initiatives such as physical distancing continue.

Pandemic Pause: Systematic Review of Cost Variables for Ambulatory Care Organizations Participating in Accountable Care Organizations.

Ambulatory health care provider organizations participating in Accountable Care Organizations (ACOs) organizations assume costs beyond typical practice operations that are directly associated with value-based care initiatives. Identifying these variables that influence such costs are essential to an organization's financial viability. To enable the U.S. healthcare system to respond to the COVID-19 pandemic CMS issued blanket waivers that permit enhanced flexibility, extension, and other emergency declaration changes to ACO reporting requirements through the unforeseen future. This relaxation and even pausing of reporting requirements encouraged the researchers to conduct a systematic review and identify variables that have influenced costs incurred by ambulatory care organizations participating in ACOs prior to the emergency declaration. The research findings identified ACO-ambulatory care variables (enhanced patient care management, health information technology improvements, and organizational ownership/reimbursement models) that helped to reduce costs to the ambulatory care organization. Additional variables (social determinants of health/environmental conditions, lack of integration/standardization, and misalignment of financial incentives) were also identified in the literature as having influenced costs for ambulatory care organizations while participating in an ACO initiative with CMS. Findings can assist ambulatory care organizations to focus on new and optimized strategies as they begin to prepare for the post-pandemic resumption of ACO quality reporting requirements once the emergency declaration is eventually lifted.

A Decade in Review: A Systematic Review of Universal Influenza Vaccines in Clinical Trials during the 2010 Decade.

On average, there are 3-5 million severe cases of influenza virus infections globally each year. Seasonal influenza vaccines provide limited protection against divergent influenza strains. Therefore, the development of a universal influenza vaccine is a top priority for the NIH. Here, we report a comprehensive summary of all universal influenza vaccines that were tested in clinical trials during the 2010-2019 decade. Of the 1597 studies found, 69 eligible clinical trials, which investigated 27 vaccines, were included in this review. Information from each trial was compiled for vaccine target, vaccine platform, adjuvant inclusion, clinical trial phase, and results. As we look forward, there are currently three vaccines in phase III clinical trials which could provide significant improvement over seasonal influenza vaccines. This systematic review of universal influenza vaccine clinical trials during the 2010-2019 decade provides an update on the progress towards an improved influenza vaccine.