Impact of Social Determinants of Health on Outcomes Following Resection for Hepatocellular Carcinoma.

BACKGROUND: We sought to determine the impact of social determinants of health (SDoH) on outcomes of patients undergoing resection for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients with HCC in the National Cancer Database who underwent resection from 2009 to 2018 were identified. SDoH associated with length of stay (LOS), 30-day readmission, and 30-day mortality were analyzed using regression analyses adjusted for confounding variables. RESULTS: Among 9235 patients, the median age (range) was 65.0 (18-90) years, 72.1% were male, and 57.9% were White. A total of 3% were uninsured, 11.1% had Medicaid, 21% resided in regions with a median household income within the lowest quartile of the US population, and 27.0% resided in regions within the lowest quartile of education level. The odds for having longer LOS were lower among patients with the highest regional education level compared with those with the lowest level [odds ratio (OR) 0.86, 95% confidence interval (CI) 0.77-0.97]. The risk of readmission was lower among patients with Medicare (OR 0.52; 95% CI 0.33-0.81), Medicaid (OR 0.52; 95% CI 0.31-0.87), or private insurance (OR 0.56; 95% CI 0.35-0.88) compared with uninsured patients. Thirty-day overall mortality was less likely among patients with Medicare (OR 0.45; 95% CI 0.27-0.75), Medicaid (OR 0.53; 95% CI 0.30-0.93), or private insurance (OR 0.40; 95% CI 0.24-0.66), and among patients with high regional income (OR 0.58; 95% CI 0.44-0.77). CONCLUSIONS: Adjusted regression analyses identified SDoH that were associated with HCC outcomes. Increased awareness of how SDoH relate to outcomes may inform strategies that attempt to account for these associations and improve patient outcomes.

The pancreatic cancer immune tumor microenvironment is negatively remodeled by gemcitabine while TGF-ß receptor plus dual checkpoint inhibition maintains antitumor immune cells.

Pancreatic ductal adenocarcinoma (PDA) tumors have a highly immunosuppressive desmoplastic tumor microenvironment (TME) where immune checkpoint inhibition (ICI) therapy has been exceptionally ineffective. Transforming growth factor-ß (TGF-ß) receptor activation leads to cancer and immune cell proliferation and phenotype, and cytokine production leading to tumor progression and worse overall survival in PDA patients. We hypothesized that TGF-ß receptor inhibition may alter PDA progression and antitumor immunity in the TME. Here, we used a syngeneic preclinical murine model of PDA to explore the impact of TGF-ß pathway inhibitor galunisertib (GAL), dual checkpoint immunotherapy (anti-PD-L1 and CTLA-4), the chemotherapy gemcitabine (GEM), and their combinations on antitumor immune responses. Blockade of TGF-ß and ICI in immune-competent mice bearing orthotopically injected murine PDA cells significantly inhibited tumor growth and was accompanied by antitumor M1 macrophage infiltration. In contrast, GEM treatment resulted in increased PDA tumor growth, decreased antitumor M1 macrophages, and decreased cytotoxic CD8+ T cell subpopulation compared to control mice. Together, these findings demonstrate the ability of TGF-ß inhibition with GAL to prime antitumor immunity in the TME and the curative potential of combining GAL with dual ICI. These preclinical results indicate that targeted inhibition of TGF-ß may enhance the efficacy of dual immunotherapy in PDA. Optimal manipulation of the immune TME with non-ICI therapy may enhance therapeutic efficacy.

Strategies to enhance the success of mid-career nurse scientists.

BACKGROUND: The mid-career nurse scientist, defined as an associate professor with/without tenure, is often faced with a multitude of challenges and opportunities PURPOSE: This paper shares strategies to assist mid-career scientists as they juggle required career demands and navigate the mid-career phase in pursuit of the rank of full professor. METHOD: A review of the literature was performed on mid-career nurse scientists. DISCUSSION: A combination of increased research responsibilities, increased institutional teaching and service demands, and dwindling support can result in a sense of overwhelm and burnout. The mid-career nurse scientist must balance several balls in the air at one time to remain successful. CONCLUSION: Strategies aligned with the Ecological Framework, focus on intrapersonal, interpersonal, institutional, organizational, and public policy domains to provide a wide scope of strategies that target the mid-career scientist and engage the larger nursing community.

A Conceptual Model of the Influence of Mindfulness-Based Interventions on Stress and Quality of Life in Patients With Chronic Conditions.

Individuals with chronic conditions are susceptible to stress-related health complications. Left unattended, chronic stress exacerbates inflammation, diminishes quality of life (QOL), and increases all-cause mortality. Here, we suggest a theoretical framework promoting the use of mindfulness-based interventions (MBIs) in patients with chronic conditions and a conceptual model of how MBIs may influence stress and QOL.

Genotype-expression interactions for BDNF across human brain regions.

BACKGROUND: Genetic variations in brain-derived neurotrophic factor (BDNF) are associated with various psychiatric disorders including depression, obsessive-compulsive disorder, substance use disorders, and schizophrenia; altered gene expression triggered by these genetic variants may serve to create these phenotypes. But genotype-expression interactions for this gene have not been well-studied across brain regions relevant for psychiatric disorders. RESULTS: At false discovery rate (FDR) of 10% (q < 0.1), a total of 61 SNPs were associated with BDNF expression in cerebellum (n = 209), 55 SNPs in cortex (n = 205), 48 SNPs in nucleus accumbens (n = 202), 47 SNPs in caudate (n = 194), and 58 SNPs in cerebellar hemisphere (n = 175). We identified a set of 30 SNPs in 2 haplotype blocks that were associated with alterations in expression for each of these 5 regions. The first haplotype block included variants associated in the literature with panic disorders (rs16917204), addiction (rs11030104), bipolar disorder (rs16917237/rs2049045), and obsessive-compulsive disorder (rs6265). Likewise, variants in the second haplotype block have been previously associated with disorders such as nicotine addiction, major depressive disorder (rs988748), and epilepsy (rs6484320/rs7103411). CONCLUSIONS: This work supports the association of variants within BDNF for expression changes in these key brain regions that may contribute to common behavioral phenotypes for disorders of compulsion, impulsivity, and addiction. These SNPs should be further investigated as possible therapeutic and diagnostic targets to aid in management of these and other psychiatric disorders.

Lessons Learned From Pairing Education-Intensive and Research-Intensive Faculty to Increase Scholarship in Nursing.

ABSTRACT: Many nurse faculty find scholarship goals difficult to achieve while also maintaining education, practice, and service duties. This article describes a partnership between education-intensive and research-intensive faculty members that increased scholarly output. Challenges included conflicting schedules and responsibilities and an increasing desire to accomplish more than was possible in the allotted time. Differences in educational preparation and experiences were found to be a facilitator that enabled the team to be more productive. An equally felt commitment to the process and dedicated meetings also helped this team to be successful.

Strategies and Resources for Increasing the PhD Pipeline and Producing Independent Nurse Scientists.

Nurse scientists play an indispensable role in developing new knowledge to advance the health of patients, families, and communities. Yet PhD nurse enrollment has significantly dropped, and many later career nurse scientists are nearing retirement. The purpose of this article is to outline potential strategies to enhance the PhD nurse pipeline. Potential strategies are identified at three distinct time points along the PhD trajectory: (a) prior to a PhD program (increasing the pipeline), (b) during a PhD program (enhancing graduation rates and transitioning into research-focused careers), and (c) in the postdoctoral or early career period (establishing scholarly independence and an active program of research). Talented students should be approached early on in their education to ascertain interest in a scientific research-based career, and all students could be engaged in research opportunities while in undergraduate programs. During a PhD program, supportive mentors are a key component for student success and may provide assistance in obtaining ongoing funding and scholarship support. Throughout doctoral study and into early career, less structured opportunities can be influential, including conference support, online and face-to-face training, and ongoing funding and scholarship support for postdoctoral study or fellowships. At each career stage, there should be a focus on designing scientifically sound nursing research that will impact outcomes in measurable and sustainable ways. We must not focus our attention only on student recruitment. Public messaging efforts are needed to raise awareness of the role of nurse researchers. In addition, several stakeholders play a role in increasing the PhD pipeline and producing independent nurse scientists, and they should be acknowledged in these efforts. The strategies described may be beneficial for any nurse contemplating a research career as well as for those who may serve as mentors to these individuals. More broadly, these strategies may be employed by colleges and universities, funding bodies, professional nursing societies, and healthcare organizations in the United States and abroad. Increasing the PhD pipeline, and fostering a more robust field of independent nurse scientists, will translate into improved patient outcomes.

The impact of plasma brain-derived neurotrophic factor concentration and weight gain after kidney transplantation.

Obesity and its related complications continue to be significant challenges for kidney transplant recipients. In previous studies, researchers have reported that brain-derived neurotrophic factor (BDNF) is closely associated with metabolic imbalance and obesity, but the role of BDNF in weight gain after kidney transplant has not been elucidated. The purpose of this pilot study was to explore the relationship between plasma BDNF levels and weight change. We examined associations between plasma BDNF levels measured at transplantation and 12 months later and measures of weight change during these 12 months in a sample of 55 kidney recipients (mean age of 48 years, 60% male, 56% African American). Of the 55 recipients, 49 had BDNF levels measured at baseline, 33 had BDNF levels measured at 12 months, and 27 had BDNF levels measured at both time points. We found that plasma BDNF levels at baseline (n = 49), but not at 12 months (n = 33), were significantly and positively correlated with the body mass index change (p = 0.037) and percentage weight change (p = 0.036). In addition, average plasma BDNF value at 12 months (307 ± 254 pg/ml) was significantly lower than at baseline (452 ± 345 pg/ml) in the 27 recipients with BDNF levels measured at both time points. Findings from this pilot work suggest that BDNF might serve as a regulator of weight change for kidney transplant related obesity.

Psychosocial Comorbidities Related to Return to Work Rates Following Aneurysmal Subarachnoid Hemorrhage.

Purpose Ability to return to work (RTW) after stroke has been shown to have positive psychosocial benefits on survivors. Although one-fifth of aneurysmal subarachnoid hemorrhage (aSAH) survivors suffer from poor psychosocial outcomes, the relationship between such outcomes and RTW post-stroke is not clear. This project explores the relationship between age, gender, race, marital status, anxiety and depression and RTW 3 and 12 months post-aSAH. Methods Demographic and clinical variables were collected from the electronic medical record at the time of aSAH admission. Anxiety and depression were assessed at 3 and 12 months post-aSAH using the State Trait Anxiety Inventory (STAI) and Beck's Depression Inventory-II (BDI-II) in 121 subjects. RTW for previously employed patients was dichotomized into yes/no at their 3 or 12 month follow-up appointment. Results Older age was significantly associated with failure to RTW at 3 and 12 months post-aSAH (p = 0.003 and 0.011, respectively). Female gender showed a trending but nonsignificant relationship with RTW at 12 months (p = 0.081). High scores of depression, State anxiety, and Trait anxiety all had significant associations with failure to RTW 12 months post-aSAH (0.007 ≤ p ≤ 0.048). At 3 months, there was a significant interaction between older age and high State or Trait anxiety with failure to RTW 12 months post-aSAH (p = 0.025, 0.042 respectively). Conclusions Patients who are older and suffer from poor psychological outcomes are at an increased risk of failing to RTW 1-year post-aSAH. Our interactive results give us information about which patients should be streamlined for therapy to target their psychosocial needs.

A Systematic Review of Barriers and Facilitators for Concussion Reporting Behavior Among Student Athletes.

Despite increasing attention to concussion safety, many young athletes still do not report concussion-like symptoms to athletic staff. This systematic review was conducted to identify barriers and facilitators to reporting of concussions by high school and collegiate athletes. The review was conducted using PubMed, SCOPUS, CINAHL Complete, and Cochrane Library. Original research articles were deemed eligible if they contained either qualitative or quantitative data on barriers and facilitators of high school and collegiate athletes self-reporting concussion symptoms to athletic staff. For those articles that met inclusion criteria, both authors critically read each article, summarized reasons given by the authors, and then categorized this information into a barrier or a facilitator of concussion-reporting behavior. Of the 878 articles returned, 24 articles met inclusion criteria. Major facilitators were female sex and younger age. Major barriers were a fear of losing current or future playing time, a misconception that concussive injury is not serious, a fear of letting one's team down, and a lack of knowledge of concussion signs and symptoms. Future interventions should address these issues, incorporate primary and secondary prevention strategies, and emphasize the long-term risks of playing while concussed.

A Prospective Study of Depression and Weight Change After Kidney Transplant.

CONTEXT: Kidney transplant recipients have great risk for gaining significant weight (upward of 10 kg) in the first year posttransplant. Clinical depression can occur in response to life situations and is associated with weight gain. OBJECTIVE: To explore the association between demographic characteristics, weight change, and depression posttransplantation. DESIGN: Secondary data analysis on longitudinal data collected for a larger observational study. Demographic characteristics, weight, and Center for Epidemiologic Studies Depression Scale (CES-D) data were obtained at baseline (BL) (time of transplantation), 6, and 12 months posttransplant. The CES-D scores were compared among time points using means, standard deviations, correlations, t tests, and chi-square as well as by multiple regression modeling. SETTING: Regional transplant center in the mid-south United States. PARTICIPANTS: Forty-seven kidney transplant recipients (55% female, 57% African American, mean age 52.5 years). Weight change ranged from -18.1 to +24.8 kg. RESULTS: In all, 62% reported baseline CES-D scores indicative of depression, with lower scores indicating less psychological distress at 6 and 12 months (47% and 49%, respectively). We found no significant differences among CES-D scores at any time point. Regression models found age, race, gender, and weight change to be predictive of CES-D scores at 6 months (P = .04, R (2) = .137). Age was the most influential (P = .008), with older individuals more likely to obtain higher CES-D scores. Since the experience of depression is common at transplant and during the first year, it is important that transplant recipients be evaluated for depression early in the recovery period.

The Role of Matrix Metalloproteinase Polymorphisms in Ischemic Stroke.

Stroke remains the fifth leading cause of mortality in the United States with an annual rate of over 128,000 deaths per year. Differences in incidence, pathogenesis, and clinical outcome have long been noted when comparing ischemic stroke among different ethnicities. The observation that racial disparities exist in clinical outcomes after stroke has resulted in genetic studies focusing on specific polymorphisms. Some studies have focused on matrix metalloproteinases (MMPs). MMPs are a ubiquitous group of proteins with extensive roles that include extracellular matrix remodeling and blood-brain barrier disruption. MMPs play an important role in ischemic stroke pathophysiology and clinical outcome. This review will evaluate the evidence for associations between polymorphisms in MMP-1, 2, 3, 9, and 12 with ischemic stroke incidence, pathophysiology, and clinical outcome. The role of polymorphisms in MMP genes may influence the presentation of ischemic stroke and be influenced by racial and ethnic background. However, contradictory evidence for the role of MMP polymorphisms does exist in the literature, and further studies will be necessary to consolidate our understanding of these multi-faceted proteins.

Measures and Influencers of Reintegration for the Stroke Patient: A Systematic Review.

ABSTRACT: BACKGROUND: Stroke survivors may experience continued difficulties with reintegration, including challenges participating in social roles and performing activities of daily living across settings (eg, home, work). This article assessed the reintegration measures currently used in this clinical population, defining factors that most influence reintegration for these persons. METHODS: A systematic review of PubMed, Scopus, and the Cumulative Index to Nursing and Allied Health Literature databases explored reintegration measures and factors influencing reintegration in stroke populations. Study inclusion criteria for this review were as follows: data-based articles (quantitative and qualitative), studies measuring reintegration or examining outcomes of reintegration, participants being adult stroke populations, and studies published in English. The resulting articles were critically analyzed, and common themes regarding barriers, facilitators, and influencers of reintegration were established. RESULTS: A total of 24 articles met the inclusion criteria and were synthesized for use in this systematic review. Across stroke populations, 13 reintegration tools were used. A few factors, including residual stroke impairments, unmet needs, social support, and sociodemographic characteristics, are currently known to influence reintegration for this population. CONCLUSION: Reintegration must be uniformly defined and measured to best support stroke survivors, and further investigation into influential factors is critical to advance this goal. This review defines current assessments and factors influencing reintegration within stroke populations. Achieving these goals is critical to optimizing reintegration efforts and designing quality-of-life-improving nursing interventions for affected persons.

Associations between concussion and more severe TBIs, mild cognitive impairment, and early-onset dementia among military retirees over 40 years.

Background and objectives: As the population of U.S. service members (SMs) who have sustained concussions and more severe traumatic brain injuries (TBIs) during military service ages, understanding the long-term outcomes associated with such injuries will provide critical information that may promote long-term assessment, support, and rehabilitation following military service. The objective of this research was to examine whether concussion and more severe TBIs are associated with greater risk of precursors to dementia (i.e., mild cognitive impairment, memory loss), early-onset dementia, and any dementia. Methods: This study used a retrospective cohort design wherein archival medical and career records from 1980 to 2020 identified U.S. military personnel who retired from military service and their corresponding Tricare-reimbursable medical encounters in inpatient and/or outpatient settings in military treatment facilities and/or purchased care settings both before and after retirement. All military personnel who served on active duty between 1980 and 2020 and were at least 45 years of age by 2020 were eligible for inclusion (N = 6,092,432). Those who were discharged from military service with a retirement designation, and were thus eligible for Tricare for Life, were included in the analytic sample (N = 1,211,972). Diagnoses of concussion and more severe TBI during active duty service recorded in inpatient settings between 1980 and 2020 and in outpatient settings from 2001 to 2020 were identified. Focal outcomes of interest included memory loss, mild cognitive impairment, Alzheimer's, Lewy Body dementia, frontotemporal dementia, and vascular dementia. Dementia diagnoses before age 65 were labeled early-onset. Results: Those with (vs. without) concussion diagnoses during military service were significantly more likely to be diagnosed with memory loss and mild cognitive impairment and any of the dementias examined. However, they were not at greater risk of being diagnosed with early-onset dementia. Discussion: Military SMs diagnosed with concussion may be at elevated risk for long-term neurodegenerative outcomes including memory loss, mild cognitive impairment, and dementia. As the population of SMs who sustained TBI during the Global War on Terror continue to age, the prevalence of dementia will increase and may bring a unique burden to the VHA.

Haptoglobin genotype is a risk factor for coronary artery disease in prediabetes: A case-control study.

Objective: Coronary artery disease (CAD) prediction remains inconsistent with many unappreciated risk factors. Haptoglobin genotype determines the haptoglobin protein's effectiveness to bind free hemoglobin and prevent oxidative stress, a contributor to atherosclerosis. The haptoglobin 2-2 genotype increases the prevalence of cardiovascular disease (CVD) approximately five times compared to the 1-1 genotype in individuals with diabetes. The risk is unknown in prediabetes. The purpose of this study was to determine an association between haptoglobin genotype and CAD in prediabetes. Methods: The researchers used case-control convenience sampling from two cardiovascular disease prevention clinics in Memphis, TN, and Spokane, WA, from January 1, 2016 to March 31, 2020. Participants were ages 35-70, had prediabetes, and free of chronic inflammatory or infectious diseases. Cases had a history of subclinical or clinical CAD, while controls did not have a history of CAD. Differences between cases and controls and among haptoglobin genotypes were analyzed using t-tests and ANOVA for continuous variables and chi-square or Fisher's exact tests for categorical variables. Associations among Hp genotypes and CAD were estimated using logistic regression. Results: The sample (N = 178; 72 cases and 106 controls) was 96 % white and 64 % male. Cases had lower total cholesterol (p = 0.0001) and high-sensitivity C-reactive protein (p = 0.021). Except for CAD, haptoglobin genotype was independent of any demographic or clinical variable. Haptoglobin 2-2 genotype had 4.0 times higher odds of CAD than haptoglobin 1-1 (p = 0.01). Conclusion: Haptoglobin 2-2 genotype had approximately four times higher odds of having CAD compared to the haptoglobin 1-1 genotype. Cases had more desirable clinical profiles, likely attributable to more aggressive treatment of traditional risk factors than controls. Haptoglobin genotype is a potentially important CAD risk factor in prediabetes (88 million Americans). Further studies are needed for interventions to reduce the oxidative stress associated with the Hp 2-2 genotype and glycosylated hemoglobin and for CAD reduction.

An overview of the genomics of metabolic syndrome.

PURPOSE: This article provides a brief overview of the diagnostic criteria and genomic risk factors for the components of metabolic syndrome (MetS). ORGANIZING CONSTRUCTS: Contributions of cardiovascular, obesity, and diabetes genomic risk factors to the development of MetS as reported in the literature have been reviewed. FINDINGS: The genomic risk factors for the development of MetS are strongly linked to the genomic risk factors that make up the components of the disease. Many of the cardiovascular and renal genomic risk factors for MetS development are similar to those found in the development of hypertension and dyslipidemia. Obesity may act as a master trigger to turn on the gene expression changes necessary for the other components of the disease. Studies in the genomics of type 2 diabetes show a number of overlapping genes and polymorphisms that influence both the development of diabetes and MetS. CONCLUSIONS: Although health practitioners now have some insights into the genomics of risk factors associated with MetS, the overall understanding of MetS remains inadequate. Clinical applications based on some of the discussed genomic risk factors are being developed but are not yet available for the diagnosis and treatment of MetS. CLINICAL RELEVANCE: A broad knowledge of the genomic contributions to disease processes will enable the clinician to better utilize genomics to assess and tailor management of patients.

Oxidative Stress Underpins Clinical, Social, and Genetic Risk Factors for Atherosclerotic Cardiovascular Disease.

Background: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide and is poorly predicted with current risk estimation tools. The biological mechanisms relating ASCVD risk factors to oxidative stress (OS) and how this accumulates ASCVD risk are misunderstood. Purpose: To develop a comprehensive conceptual model explaining how expanded clinical, social, and genetic ASCVD risk factors accumulate ASCVD risk through OS. Conclusions: OS (primarily from excess reactive oxygen species) and inflammation are present along the entire ASCVD pathophysiologic continuum. An expanded list of clinical and social ASCVD risk factors (including hypertension, obesity, diabetes, kidney disease, inflammatory diseases, substance use, poor nutrition, psychosocial stress, air pollution, race, and genetic ancestry) influence ASCVD largely through increased OS. Many risk factors exert a positive feedback mechanism to increase OS. One genetic risk factor, haptoglobin (Hp) genotype, is associated with higher ASCVD risk in diabetes and hypothesized to do the same in those with insulin resistance due to the Hp 2-2 genotype increasing OS. Implications: Understanding the biological mechanisms of OS informs how these ASCVD risk factors relate to each other and compound ASCVD risk. Individualized ASCVD risk estimation should include a comprehensive, holistic perspective of risk factors to better address the clinical, social, and genetic influences of OS. Preventing and reducing OS is key to preventing ASCVD development or progression.

An Integrative Review of the Utilization of the Perceived Stress Scale in Stroke Recovery.

ABSTRACT: BACKGROUND: Stroke survivors (SS) may experience alterations in physical and cognitive processes that increase stress and reduce well-being. Timely and accurate measurement of stress throughout the continuum of recovery is necessary to inform targeted interventions that will improve quality of life for this group. OBJECTIVE: The aim of this study was to describe the utilization of the Perceived Stress Scale (PSS) during recovery in SS. METHODS: A comprehensive literature search was conducted using CINAHL, PsycINFO, PubMed, and Scopus databases. Studies were included if they captured primary data collection using any version of the PSS at any time point in the poststroke recovery period and were published in English between 2011 and 2022. Systematic reviews and meta-analyses were excluded. Evidence was synthesized, and themes were discussed. RESULTS: Among 397 studies, a total of 13 met inclusion criteria. Of these, 8 were cross-sectional studies, 3 were longitudinal studies, 1 was a randomized controlled trial, and the remaining study was a prospective nonrandomized trial. The PSS-10 (n = 7, 54%) was the most used version of the instrument, followed by the PSS-14 (n = 3, 23%) and PSS-4 (n = 2, 15.4%), with the modified PSS-10 being used in only 1 (7.6%) study. The PSS surveys were administered at various time points, ranging from the first day of admission to 3, 6, 9, or 12 months after discharge. Perceived stress may continue to negatively influence SS's psychological and physical well-being throughout the chronic phase of recovery. CONCLUSIONS: Stress is a unique and individualized experience that influences recovery trajectories in SS, an experience often overlooked or marginalized by clinicians and healthcare providers. To help mobilize strategies to achieve long-term health and wellness goals, future studies should explore and tailor interventions to minimize the influence of stress, as identified by the PSS, on well-being and quality of life during poststroke recovery.