Health-related quality of life in older patients with heart failure from before to early after advanced surgical therapies: Findings from the SUSTAIN-IT study

BACKGROUND: Restoring health-related quality of life (HRQOL) is a therapeutic goal for older patients with advanced heart failure. We aimed to describe change in HRQOL in older patients (60-80 years) awaiting heart transplantation (HT) with or without pretransplant mechanical circulatory support (MCS) or scheduled for long-term MCS, if ineligible for HT, from before to 6 months after these surgeries and identify factors associated with change. METHODS: Patients from 13 US sites completed the EuroQol 5-dimension 3L questionnaire and Kansas City Cardiomyopathy Questionnaire-12 at baseline and 3 and 6 months after HT or long-term MCS. Analyses included univariate comparisons and multivariable linear regression. RESULTS: Among 305 participants (cohort mean age=66.2±4.7 years, 78% male, 84% White, 55% New York Heart Association class IV), 161 underwent HT (n=68 with and n=93 without pretransplant MCS), and 144 received long-term MCS. From baseline to 3 months, EuroQol 5-dimension visual analog scale scores improved in HT patients without pretransplant MCS (54.5±24.3 versus 75.9±16.0, CONCLUSIONS: In older heart failure patients, HRQOL improved from before to early after HT and long-term MCS. At 6 postoperative months, HRQOL of long-term MCS patients was lower than one or both HT groups. Understanding change in HRQOL from before to early after these surgeries may enhance decision-making and guide patient care. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02568930

Health-related quality of life in older patients with advanced heart failure: Findings from the SUSTAIN-IT study

Background There is a paucity of research describing health-related quality of life (HRQOL) in older adults considered for advanced heart failure surgical therapies. Using data from our SUSTAIN-IT (Sustaining Quality of Life of the Aged: Heart Transplant or Mechanical Support) study, we aimed to compare HRQOL among 3 groups of older (60-80 years) patients with heart failure before heart transplantation (HT) or long-term mechanical circulatory support (MCS) and identify factors associated with HRQOL: (1) HT candidates with MCS, (2) HT candidates without MCS, or (3) candidates ineligible for HT and scheduled for long-term MCS. Methods and Results Patients from 13 US sites completed assessments, including self-reported measures of HRQOL (EuroQol-5 Dimension Questionnaire, Kansas City Cardiomyopathy Questionnaire-12), depressive symptoms (Personal Health Questionnaire-8), anxiety (State-Trait Anxiety Inventory-state form), cognitive status (Montreal Cognitive Assessment), and performance-based measures (6-minute walk test and 5-m gait speed). Analyses included ANOVA,

Heart Failure Symptom Biology in Response to Ventricular Assist Device Implantation.

BACKGROUND: We have a limited understanding of the biological underpinnings of symptoms in heart failure (HF), particularly in response to left ventricular assist device (LVAD) implantation. OBJECTIVE: The aim of this study was to quantify the degree to which symptoms and biomarkers change in parallel from before implantation through the first 6 months after LVAD implantation in advanced HF. METHODS: This was a prospective cohort study of 101 patients receiving an LVAD for the management of advanced HF. Data on symptoms (dyspnea, early and subtle symptoms [HF Somatic Perception Scale], pain severity [Brief Pain Inventory], wake disturbance [Epworth Sleepiness Scale], depression [Patient Health Questionnaire], and anxiety [Brief Symptom Inventory]) and peripheral biomarkers of myocardial stretch, systemic inflammation, and hypervolumetric mechanical stress were measured before implantation with a commercially available LVAD and again at 30, 90, and 180 days after LVAD implantation. Latent growth curve and parallel process modeling were used to describe changes in symptoms and biomarkers and the degree to which they change in parallel in response to LVAD implantation. RESULTS: In response to LVAD implantation, changes in myocardial stretch were closely associated with changes in early and subtle physical symptoms as well as depression, and changes in hypervolumetric stress were closely associated with changes in pain severity and wake disturbances. Changes in systemic inflammation were not closely associated with changes in physical or affective symptoms in response to LVAD implantation. CONCLUSIONS: These findings provide new insights into the many ways in which symptoms and biomarkers provide concordant or discordant information about LVAD response

Genetic evidence for the interaction between Bacillus anthracis-encoded phage receptors and their cognate phage-encoded receptor binding proteins

Bacteriophages such as γ and AP50c have been shown to infect strains of Bacillus anthracis with high specificity, and this feature has been exploited in the development of bacterial detection assays. To better understand the emergence of phage resistance, and thus the potential failure of such assays, it is important to identify the host and phage receptors necessary for attachment and entry. Using genetic approaches, the bacterial receptors of AP50c and γ have been identified as sap and GamR, respectively. A second AP50c-like phage, Wip1, also appears to use sap as a receptor. In parallel with this work, the cognate phage-encoded receptor binding proteins (RBPs) have also been identified (Gp14 for γ, P28 for AP50c, and P23 for Wip1); however, the strength of evidence supporting these protein–protein interactions varies, necessitating additional investigation. Here, we present genetic evidence further supporting the interaction between sap and the RBPs of AP50c and Wip1 using fluorescently tagged proteins and a panel of B. anthracis mutants. These results showed that the deletion of the sap gene, as well as the deletion of csaB, whose encoded protein anchors sap to the bacterial S-layer, resulted in the loss of RBP binding. Binding could then be rescued by expressing these genes in trans. We also found that the RBP of the γ-like prophage λBa03 relied on csaB activity for binding, possibly by a different mechanism. RBPλBa03 binding to B. anthracis cells was also unique in that it was not ablated by heat inactivation of vegetative cells, suggesting that its receptor is still functional following incubation at 98°C. These results extend our understanding of the diverse attachment and entry strategies used by B. anthracis phages, enabling future assay development

Decision making in advanced heart failure: A scientific statement from the american heart association

Shared decision making for advanced heart failure has become both more challenging and more crucial as duration of disease and treatment options have increased. High-quality decisions are chosen from medically reasonable options and are aligned with values, goals, and preferences of an informed patient. The top 10 things to know about decision making in advanced heart failure care are listed in Table 1

Biomarkers as Common Data Elements for Symptom and Selfâ Management Science

PurposeBiomarkers as common data elements (CDEs) are important for the characterization of biobehavioral symptoms given that once a biologic moderator or mediator is identified, biologically based strategies can be investigated for treatment efforts. Just as a symptom inventory reflects a symptom experience, a biomarker is an indicator of the symptom, though not the symptom per se. The purposes of this position paper are to (a) identify a â minimum setâ of biomarkers for consideration as CDEs in symptom and selfâ management science, specifically biochemical biomarkers; (b) evaluate the benefits and limitations of such a limited array of biomarkers with implications for symptom science; (c) propose a strategy for the collection of the endorsed minimum set of biologic samples to be employed as CDEs for symptom science; and (d) conceptualize this minimum set of biomarkers consistent with National Institute of Nursing Research (NINR) symptoms of fatigue, depression, cognition, pain, and sleep disturbance.Design and MethodsFrom May 2016 through January 2017, a working group consisting of a subset of the Directors of the NINR Centers of Excellence funded by P20 or P30 mechanisms and NINR staff met bimonthly via telephone to develop this position paper suggesting the addition of biomarkers as CDEs. The full group of Directors reviewed drafts, provided critiques and suggestions, recommended the minimum set of biomarkers, and approved the completed document. Best practices for selecting, identifying, and using biological CDEs as well as challenges to the use of biological CDEs for symptom and selfâ management science are described. Current platforms for sample outcome sharing are presented. Finally, biological CDEs for symptom and selfâ management science are proposed along with implications for future research and use of CDEs in these areas.FindingsThe recommended minimum set of biomarker CDEs include proâ and antiâ inflammatory cytokines, a hypothalamicâ pituitaryâ adrenal axis marker, cortisol, the neuropeptide brainâ derived neurotrophic factor, and DNA polymorphisms.ConclusionsIt is anticipated that this minimum set of biomarker CDEs will be refined as knowledge regarding biologic mechanisms underlying symptom and selfâ management science further develop. The incorporation of biological CDEs may provide insights into mechanisms of symptoms, effectiveness of proposed interventions, and applicability of chosen theoretical frameworks. Similarly, as for the previously suggested NINR CDEs for behavioral symptoms and selfâ management of chronic conditions, biological CDEs offer the potential for collaborative efforts that will strengthen symptom and selfâ management science.Clinical RelevanceThe use of biomarker CDEs in biobehavioral symptoms research will facilitate the reproducibility and generalizability of research findings and benefit symptom and selfâ management science.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143764/1/jnu12378.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143764/2/jnu12378_am.pd

Relationship of EMAST and Microsatellite Instability Among Patients with Rectal Cancer

Elevated microsatellite instability at selected tetranucleotide repeats (EMAST) is a genetic signature identified in 60% of sporadic colon cancers and may be linked with heterogeneous expression of the DNA mismatch repair (MMR) protein hMSH3. Unlike microsatellite instability-high (MSI-H) in which hypermethylation of hMLH1 occurs followed by multiple susceptible gene mutations, EMAST may be associated with inflammation and subsequent relaxation of MMR function with the biological consequences not known. We evaluated the prevalence of EMAST and MSI in a population-based cohort of rectal cancers, as EMAST has not been previously determined in rectal cancers. We analyzed 147 sporadic cases of rectal cancer using five tetranucleotide microsatellite markers and National-Cancer-Institute-recommended MSI (mononucleotide and dinucleotide) markers. EMAST and MSI determinations were made on analysis of DNA sequences of the polymerase chain reaction products and determined positive if at least two loci were found to have frame-shifted repeats upon comparison between normal and cancer samples from the same patient. We correlated EMAST data with race, gender, and tumor stage and examined the samples for lymphocyte infiltration. Among this cohort of patients with rectal cancer (mean age 62.2 ± 10.3 years, 36% female, 24% African American), 3/147 (2%) showed MSI (three males, two African American) and 49/147 (33%) demonstrated EMAST. Rectal tumors from African Americans were more likely to show EMAST than Caucasians (18/37, 49% vs. 27/104, 26%, p = 0.014) and were associated with advanced stage (18/29, 62% EMAST vs. 18/53, 37%, non-EMAST p = 0.02). There was no association between EMAST and gender. EMAST was more prevalent in rectal tumors that showed peri-tumoral infiltration compared to those without (30/49, 60% EMAST vs. 24/98, 25% non-EMAST, p = 0.0001). EMAST in rectal cancer is common and MSI is rare. EMAST is associated with African-American race and may be more commonly seen with metastatic disease. The etiology and consequences of EMAST are under investigation, but its association with immune cell infiltration suggests that inflammation may play a role for its development

The META tool optimizes metagenomic analyses across sequencing platforms and classifiers

A major challenge in the field of metagenomics is the selection of the correct combination of sequencing platform and downstream metagenomic analysis algorithm, or “classifier”. Here, we present the Metagenomic Evaluation Tool Analyzer (META), which produces simulated data and facilitates platform and algorithm selection for any given metagenomic use case. META-generated in silico read data are modular, scalable, and reflect user-defined community profiles, while the downstream analysis is done using a variety of metagenomic classifiers. Reported results include information on resource utilization, time-to-answer, and performance. Real-world data can also be analyzed using selected classifiers and results benchmarked against simulations. To test the utility of the META software, simulated data was compared to real-world viral and bacterial metagenomic samples run on four different sequencers and analyzed using 12 metagenomic classifiers. Lastly, we introduce “META Score”: a unified, quantitative value which rates an analytic classifier’s ability to both identify and count taxa in a representative sample

Decision Making in Advanced Heart Failure: A Scientific Statement From the American Heart Association

Shared decision making for advanced heart failure has become both more challenging and more crucial as duration of disease and treatment options have increased. High-quality decisions are chosen from medically reasonable options and are aligned with values, goals, and preferences of an informed patient