Lifestyle Medicine: Prevention, Treatment, and Reversal of Disease.

Lifestyle medicine (LM) expands the scope of preventive medicine by focusing on the promotion of healthy lifestyles while preventing, treating, and reversing the vast majority of chronic diseases caused by behaviors and environmental factors. LM focuses on six pillars-a plant-predominant eating pattern; physical movement; restorative sleep; management of stress; avoidance of risky substances; and positive social connections. Advances in LM competencies, education, certification, resources, and practice models are accelerating with a particular need and focus on underserved and most seriously impacted patients and communities. A comprehensive and integrated strategy addressing "whole person health" is emerging as a compelling framework for providers and health systems which combines a foundational commitment to prevention with a systematic approach to the actual and root causes of premature disease, disability, and death.

Cardiac Myeloid Sarcoma: A 1-kg Heart.

A 53-year-old man with a background of acute myelomonocytic leukemia in remission presented with pleurisy. Repeat transthoracic echocardiography over several weeks revealed thickening left ventricular walls and decreasing systolic function. He died of decompensated heart failure due to cardiac myeloid sarcoma, with autopsy revealing an enlarged heart weighing >1 kg. (Level of Difficulty: Intermediate.).

Impact of Physician Referral to Health Coaching on Patient Engagement and Health Risks: An Observational Study of UPMC's Prescription for Wellness.

PURPOSE: Evaluate impact of physician referral to health coaching on patient engagement and health risk reduction. DESIGN: Four-year retrospective, observational cohort study with propensity-matched pair comparisons. SETTING: Integrated delivery and finance system in Pittsburgh, Pennsylvania. SAMPLE: 10 457 adult insured members referred to health coaching by their physician; 37 864 other members identified for health coaching through insurer-initiated outreach. INTERVENTION: Practice-based, technology-supported workflow and process for physician prescribing of health coaching during regular office visit, with follow-up on patient's progress and implementation supports. MEASURES: Patient engagement based on completion of pre-enrollment assessment, formal enrollment in health coaching, completion of required sessions, health risk levels, and number of health risks pre- and post-health coaching referral. ANALYSIS: Difference-in-difference analysis to assess change in health risk levels and number of health risks pre- and post-health coaching and probability weighting to control for potential confounding between groups. RESULTS: Members referred by a physician were significantly more likely to enroll in a health coaching program (21.0% vs 6.0%, P < .001) and complete the program requirements (8.5% vs 2.7%, P < .001) than when referred by insurer-initiated outreach; significant within group improvement in health risk levels from baseline (P < .001) was observed for both the groups. CONCLUSIONS: Patients are significantly more likely to engage in health coaching when a referral is made by a physician; engagement in health coaching significantly improves health risk levels.

Prioritized Research for the Prevention, Treatment, and Reversal of Chronic Disease: Recommendations From the Lifestyle Medicine Research Summit.

Declining life expectancy and increasing all-cause mortality in the United States have been associated with unhealthy behaviors, socioecological factors, and preventable disease. A growing body of basic science, clinical research, and population health evidence points to the benefits of healthy behaviors, environments and policies to maintain health and prevent, treat, and reverse the root causes of common chronic diseases. Similarly, innovations in research methodologies, standards of evidence, emergence of unique study cohorts, and breakthroughs in data analytics and modeling create new possibilities for producing biomedical knowledge and clinical translation. To understand these advances and inform future directions research, The Lifestyle Medicine Research Summit was convened at the University of Pittsburgh on December 4-5, 2019. The Summit's goal was to review current status and define research priorities in the six core areas of lifestyle medicine: plant-predominant nutrition, physical activity, sleep, stress, addictive behaviors, and positive psychology/social connection. Forty invited subject matter experts (1) reviewed existing knowledge and gaps relating lifestyle behaviors to common chronic diseases, such as cardiovascular disease, diabetes, many cancers, inflammatory- and immune-related disorders and other conditions; and (2) discussed the potential for applying cutting-edge molecular, cellular, epigenetic and emerging science knowledge and computational methodologies, research designs, and study cohorts to accelerate clinical applications across all six domains of lifestyle medicine. Notably, federal health agencies, such as the Department of Defense and Veterans Administration have begun to adopt "whole-person health and performance" models that address these lifestyle and environmental root causes of chronic disease and associated morbidity, mortality, and cost. Recommendations strongly support leveraging emerging research methodologies, systems biology, and computational modeling in order to accelerate effective clinical and population solutions to improve health and reduce societal costs. New and alternative hierarchies of evidence are also be needed in order to assess the quality of evidence and develop evidence-based guidelines on lifestyle medicine. Children and underserved populations were identified as prioritized groups to study. The COVID-19 pandemic, which disproportionately impacts people with chronic diseases that are amenable to effective lifestyle medicine interventions, makes the Summit's findings and recommendations for future research particularly timely and relevant.

The impact of genetic counseling on patient engagement in a specialty cancer clinic.

The identification of patient outcomes unique to the field of genetic counseling has become a recent priority of the profession. Current health-care efforts have targeted patient engagement as an outcome capable of improving population health and reducing health-care costs. This study analyzed patient engagement levels among 182 participants who underwent genetic counseling for gastrointestinal (GI) cancer risk assessment in an outpatient specialty clinic. Patients seen at the UPMC Hereditary GI Tumor Program completed a validated patient engagement measure, the Altarum Consumer Engagement (ACE), prior to undergoing genetic counseling and again three months after enrollment. Paired t test analysis was conducted to assess the changes in Total ACE scores, and within the following three domains: Navigation, Informed Choice, and Commitment. In the sample of 182 participants, Total ACE scores increased after genetic counseling (by 5.7%; p < .0001), as did all three domains (Commitment p = .0008; Navigation p = .0008; and Informed Choice p = .0016). This study is the first known report of patient engagement levels in individuals undergoing genetic counseling in a specialty cancer clinic and suggests that genetic counseling improves patient engagement levels.

An Evaluation of Lifestyle Health Coaching Programs Using Trained Health Coaches and Evidence-Based Curricula at 6 Months Over 6 Years.

PURPOSE: Describe health plan member-level participation, completion, and 6-month outcomes for 5 lifestyle health coaching programs offered by an integrated delivery and financing system (IDFS) over 6 years. DESIGN: Case series study of 5 lifestyle programs with 180-day follow-up. SETTING: Large Western PA integrated delivery and financing system (IDFS) deployed multiple coaching modalities for diverse insurance-member enrolled population. PARTICIPANTS: A total of 14 591 health plan members choosing a lifestyle health coaching program. INTERVENTION: Evidence- and curriculum-based lifestyle health coaching programs delivered by 1 of 4 interactive modalities. MEASURES: A single metric was used as an overall indicator of clinical success for each program. Success measures include a ≥5% reduction of self-reported baseline weight, meeting physical activity guidelines, and 7-day point prevalence abstinence from tobacco. For stress and nutrition, where no single target measure exists, a metric was created that represented a net improvement across all key outcomes measured. ANALYSIS: The proportion of members meeting target outcomes were calculated and described across all time points and modalities. RESULTS: At 180 days, 77% of enrolled members reported reduced stress, 7% quit tobacco, 50.5% met physical activity guidelines, 65.2% improved nutrition, and 44.2% lost 5% or more of baseline weight. CONCLUSION: This evaluation describes the real-world effectiveness of evidence- and curriculum-based lifestyle improvement programs delivered by trained health coaches to a diverse health plan member population.

A non-canonical ESCRT pathway, including histidine domain phosphotyrosine phosphatase (HD-PTP), is used for down-regulation of virally ubiquitinated MHC class I.

The Kaposi's sarcoma-associated herpes virus (KSHV) K3 viral gene product effectively down-regulates cell surface MHC class I. K3 is an E3 ubiquitin ligase that promotes Lys(63)-linked polyubiquitination of MHC class I, providing the signal for clathrin-mediated endocytosis. Endocytosis is followed by sorting into the intralumenal vesicles (ILVs) of multivesicular bodies (MVBs) and eventual delivery to lysosomes. The sorting of MHC class I into MVBs requires many individual proteins of the four endosomal sorting complexes required for transport (ESCRTs). In HeLa cells expressing the KSHV K3 ubiquitin ligase, the effect of RNAi-mediated depletion of individual proteins of the ESCRT-0 and ESCRT-I complexes and three ESCRT-III proteins showed that these are required to down-regulate MHC class I. However, depletion of proteins of the ESCRT-II complex or of the ESCRT-III protein, VPS20 (vacuolar protein sorting 20)/CHMP6 (charged MVB protein 6), failed to prevent the loss of MHC class I from the cell surface. Depletion of histidine domain phosphotyrosine phosphatase (HD-PTP) resulted in an increase in the cell surface concentration of MHC class I in HeLa cells expressing the KSHV K3 ubiquitin ligase. Rescue experiments with wild-type (WT) and mutant HD-PTP supported the conclusion that HD-PTP acts as an alternative to ESCRT-II and VPS20/CHMP6 as a link between the ESCRT-I and those ESCRT-III protein(s) necessary for ILV formation. Thus, the down-regulation of cell surface MHC class I, polyubiquitinated by the KSHV K3 ubiquitin ligase, does not employ the canonical ESCRT pathway, but instead utilizes an alternative pathway in which HD-PTP replaces ESCRT-II and VPS20/CHMP6.

ESCRT proteins and the regulation of endocytic delivery to lysosomes.

In mammalian cells, there is evidence of cargo specificity in the requirement for particular ESCRT (endosomal sorting complex required for transport) proteins to sort cargo into the luminal vesicles of MVBs (multivesicular bodies). We have focussed on studying the ESCRT requirements for delivery of MHC class I to lysosomes following polyubiquitination by the Kaposi's sarcoma-associated herpesvirus protein K3. Down-regulation of polyubiquitinated cell-surface MHC class I in HeLa cells stably expressing K3 is achieved via clathrin-mediated endocytosis, followed by sorting into the luminal vesicles of MVBs and eventual delivery to lysosomes. Depletion of ESCRT-I and some ESCRT-III components interferes with this sorting and allows recycling of MHC class I to the cell surface. Depletion of ESCRT-II components has no effect on K3-mediated down-regulation of MHC class I and no gross morphological effect on endocytic compartments. Thus virally polyubiquitinated MHC class I does not require all of the ESCRT proteins in order to be sorted into the luminal vesicles of MVBs. However, there may be a further requirement for ESCRT-III proteins to ensure the efficient fusion of MVBs with lysosomes.