Citations

Background: Data from the CDC show that approximately one-quarter of adults have elevated triglyceride (TG) levels. Recent trials have demonstrated that pharmacologic treatment of high TG levels, in patients already on statin therapy, reduces the rate of major vascular events such as myocardial infarction and stroke (REDUCE-IT trial). We sought to assess how often patients with asymptomatic carotid stenosis (CS) have elevated TG levels and factors associated with high TG values. Methods: Patients enrolled in the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST 2) were analyzed. Baseline lipid profiles were evaluated to determine high TG treatment eligibility as per the REDUCE-IT trial. We also evaluated baseline use of pharmacologic treatment for high TG levels. Demographic factors and baseline medical conditions were studied in relation to high (>150 mg/dl) TG values. Chi square and t tests were used to assess baseline factors and abnormal TG values. Results: As of August 10, 2020, 1655 of 1689 randomized patients (mean age 69.7 years, 61% men) had baseline lipid profiles suitable for analysis. Treatment eligibility according to REDUCE-IT (LDL 41-100 mg/dl, TG>150 mg/dl) was present in 21% (345) of subjects. In these patients, the median TG value was 205 (IQR 93) mg/dl. Fibrate medications were used at baseline in 4.5% of patients. Analysis of demographic and medical history factors and TG values greater than 150 mg/dl is found in the Table. There was significant positive correlation between baseline hemoglobin A1C and triglyceride values (p<0.0001) Conclusions: One in five patients in CREST 2 has TG values that potentially justify pharmacologic treatment. Elevated TG levels are most correlated with diabetes, hypertension, obesity, decreased physical activity, and heart disease. Clinicians should investigate treatment of elevated TG levels as a component of intensive medical therapy for stroke prevention.

Fibrillary glomerulonephritis (FGN) and complement 3 glomerulopathy (C3G) are rare forms of glomerulonephritis with distinct aetiologies. Both FGN and C3G can present with nephritic syndrome. FGN is associated with autoimmune disease, dysproteinaemia, malignancy and hepatitis C infection. C3G is caused by the unregulated activation of the alternative complement pathway. We present a rare case of diffuse necrotising crescentic glomerulonephritis with dominant C3 glomerular staining on immunofluorescence—consistent with C3G—but electron microscopy (EM) findings of randomly oriented fibrils with a mean diameter of 14 nm and positive immunohistochemistry for DNAJB9—suggestive of FGN. To the best of our knowledge, this is the first reported case of FGN to show dominant C3 glomerular deposits. This case report reaffirms the utility of EM in the evaluation of nephritic syndrome and highlights the value of DNAJB9—a novel biomarker with a sensitivity and specificity near 100% for FGN.

Abstract Immunosuppression of unknown etiology is a hallmark feature of glioblastoma (GBM) and is characterized by decreased CD4 T cell counts and down regulation of MHC class II expression on peripheral blood monocytes in patients. This immunosuppression is a critical barrier to the successful development of immunotherapies for GBM. We recapitulated the immunosuppression observed in GBM patients in the C57BL/6 mouse and investigated the etiology of low CD4 T cell counts. We determined that thymic involution was a hallmark feature of immunosuppression in three distinct models of CNS cancer, including mice harboring GL261 glioma, B16 melanoma, and in a spontaneous model of Diffuse Intrinsic Pontine Glioma (DIPG). In addition to thymic involution, we determined that tumor growth in the brain induced significant splenic involution, reductions in peripheral T cells, reduced MHC class II expression on hematopoietic cells, and a modest increase in bone marrow resident CD4 T cells with a naïve phenotype. Using parabiosis we report that thymic involution, declines in peripheral T cell counts, and reduced MHC class II expression levels were mediated through circulating blood-derived factors. Conversely, T cell sequestration in the bone marrow was not governed through circulating factors. Serum isolated from glioma-bearing mice potently inhibited proliferation and functions of T cells both in vitro and in vivo. Interestingly, the factor responsible for immunosuppression in serum is nonsteroidal and of high molecular weight. Through further analysis of neurological disease models, we determined that the aforementioned immunosuppression was not unique to cancer itself, but rather occurs in response to CNS injury. Noncancerous acute neurological insults also induced significant thymic involution and rendered serum immunosuppressive. Both thymic involution and serum-derived immunosuppression were reversible upon clearance of brain insults. These findings demonstrate that CNS cancers cause multifaceted immunosuppression and pinpoint circulating factors as a target of intervention to restore immunity.

AbstractClinical decision-making is based on knowledge, expertise, and authority, with clinicians approving almost every intervention—the starting point for delivery of “All the right care, but only the right care,” an unachieved healthcare quality improvement goal. Unaided clinicians suffer from human cognitive limitations and biases when decisions are based only on their training, expertise, and experience. Electronic health records (EHRs) could improve healthcare with robust decision-support tools that reduce unwarranted variation of clinician decisions and actions. Current EHRs, focused on results review, documentation, and accounting, are awkward, time-consuming, and contribute to clinician stress and burnout. Decision-support tools could reduce clinician burden and enable replicable clinician decisions and actions that personalize patient care. Most current clinical decision-support tools or aids lack detail and neither reduce burden nor enable replicable actions. Clinicians must provide subjective interpretation and missing logic, thus introducing personal biases and mindless, unwarranted, variation from evidence-based practice. Replicability occurs when different clinicians, with the same patient information and context, come to the same decision and action. We propose a feasible subset of therapeutic decision-support tools based on credible clinical outcome evidence: computer protocols leading to replicable clinician actions (eActions). eActions enable different clinicians to make consistent decisions and actions when faced with the same patient input data. eActions embrace good everyday decision-making informed by evidence, experience, EHR data, and individual patient status. eActions can reduce unwarranted variation, increase quality of clinical care and research, reduce EHR noise, and could enable a learning healthcare system.

AbstractBackgroundInterdisciplinary cognitive behavioural therapy (CBT) for chronic pain is effective at improving function, mood and pain interference among individuals with disabling chronic pain. Traditionally, CBT assumes that cognitive change is an active therapeutic ingredient in the determination of treatment outcome. Pain catastrophizing, a cognitive response style that views the experience of pain as uncontrollable, permanent and destructive, has been identified as an important maladaptive cognition which contributes to difficulties with the management of chronic pain. Consequently, pain catastrophizing is commonly targeted in CBT for chronic pain.ObjectivesTo examine change trajectories in pain catastrophizing during treatment and assess the relevance of these trajectories to outcomes at posttreatment.MethodsParticipants included individuals with chronic pain (N = 463) who completed a 3‐week program of interdisciplinary CBT. Pain catastrophizing was assessed weekly over the 3 weeks of treatment and latent growth curve modelling was used to identify trajectories of change.ResultsFindings indicated the presence of two classes of linear change, one with a significant negative slope in pain catastrophizing (i.e. improved class) and the other with a non‐significant slope (i.e. unchanged class). Next, latent growth mixture modelling examined treatment outcome in relation to class membership. These results indicated that individuals in the ‘improved’ PCS class had significantly greater improvement in pain interference and mood, as well as physical and mental quality of life compared to the ‘unchanged’ class.ConclusionsImplications for our findings, in relation to the CBT model, are discussed.

Abstract Immunosuppression of unknown aetiology is a hallmark feature of glioblastoma and is characterized by decreased CD4 T-cell counts and downregulation of major histocompatibility complex class II expression on peripheral blood monocytes in patients. This immunosuppression is a critical barrier to the successful development of immunotherapies for glioblastoma. We recapitulated the immunosuppression observed in glioblastoma patients in the C57BL/6 mouse and investigated the aetiology of low CD4 T-cell counts. We determined that thymic involution was a hallmark feature of immunosuppression in three distinct models of brain cancer, including mice harbouring GL261 glioma, B16 melanoma, and in a spontaneous model of diffuse intrinsic pontine glioma. In addition to thymic involution, we determined that tumour growth in the brain induced significant splenic involution, reductions in peripheral T cells, reduced MHC II expression on blood leucocytes, and a modest increase in bone marrow resident CD4 T cells. Using parabiosis we report that thymic involution, declines in peripheral T-cell counts, and reduced major histocompatibility complex class II expression levels were mediated through circulating blood-derived factors. Conversely, T-cell sequestration in the bone marrow was not governed through circulating factors. Serum isolated from glioma-bearing mice potently inhibited proliferation and functions of T cells both in vitro and in vivo. Interestingly, the factor responsible for immunosuppression in serum is non-steroidal and of high molecular weight. Through further analysis of neurological disease models, we determined that the immunosuppression was not unique to cancer itself, but rather occurs in response to brain injury. Non-cancerous acute neurological insults also induced significant thymic involution and rendered serum immunosuppressive. Both thymic involution and serum-derived immunosuppression were reversible upon clearance of brain insults. These findings demonstrate that brain cancers cause multifaceted immunosuppression and pinpoint circulating factors as a target of intervention to restore immunity.

Abstract Purpose:: “No Squeeze Can Defeat Me: Mammograms for Life!” (locally, “My Life Matters: Mammograms for Life!”) was funded 2016-2019 by the Minnesota State Department of Health. It implemented a low-cost, low-tech intervention that used theory-based messaging to increase tribal women’s participation in annual mammograms and their adherence to local screening guidelines. Messaging was grounded in elements of theoretical models of health behavior that our previous research showed significantly differentiated adherent women from non-adherent women. Procedures: An 8-member tribal Community Advisory Project Board, including a 3-person Project Implementation Team, guided and carried out the intervention. The team developed and distributed 48 unique posters and placed 4-5 new posters every 6-8 weeks in 82 locations across four reservation communities. A convenience sample of women evaluated the posters. Posters had varied messages that were shaped by at least one influential element and theoretical model (e.g., Perceived Benefit from the Health Beliefs Model). 84% of displayed posters contained images of adherent tribal women. Pairwise associations of survey variables were examined using Fisher’s exact tests. Results: 229 women evaluated posters (32% under the age of 40, 64% between 40-70 years, 4% older than 70). Approximately 80% of women age 40 and older reported having at least one mammogram in their lifetime. 71% of all women said they learned something new. 96% of women said messages were personally important and 99% thought them important for other women. Of women finding the messages personally important, 99% were greater than age 40 compared to 90% who were less than age 40 (p=0.002). In those reporting they learned something new, 98% were greater than age 40 compared to 91% who were less than 40 (p=0.05). 97% of women said they would continue reading the messages when new ones were posted, underscoring the interest raised by the intervention. 164 women reported recognizing women featured on a poster. Of these, 77% said that recognition made the poster more interesting; only 2 said it made the poster less interesting. When asked if they would be more or less willing to get a mammogram if they knew others got one every year, 63% of women said they would get one regardless, 34% would be more willing, less than 1% would be less willing, and 3% said they would not get a mammogram regardless. Conclusions: Overall, women very positively regarded the posters. The sample was diverse by age, with almost one-third not yet age-eligible for screening. Across all ages and screening histories, a great majority of women agreed: 1) the posters were personally important and important for others; 2) were interested in seeing additional posters; and 3) appreciated seeing photos of adherent women on them. With 34% of viewers being more inclined to get mammograms upon knowing of others who had them, increases in monthly mammograms may be expected. Citation Format: Ann Nicometo, Robert A. Vierkant, Wesley O. Petersen. A tribal-academic multi-theory-driven messaging intervention to increase mammography participation is well-received by community women [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B018.

Abstract Context Chronic opioid use may lead to adrenal insufficiency because of central suppression of the hypothalamic-pituitary-adrenal axis. However, the prevalence of opioid-induced adrenal insufficiency (OIAI) is unclear. Objective To determine the prevalence of OIAI and to identify predictors for the development of OIAI in patients taking opioids for chronic pain. Design Cross-sectional study, 2016-2018. Setting Referral center. Patients Adult patients taking chronic opioids admitted to the Pain Rehabilitation Center. Main outcome measure Diagnosis of OIAI was considered if positive case detection (cortisol &lt; 10 mcg/dL, ACTH &lt; 15 pg/mL, and dehydroepiandrosterone sulfate &lt; 25 mcg/dL), and confirmed after endocrine evaluation. Daily morphine milligram equivalent (MME) was calculated. Results In 102 patients (median age, 53 years [range, 22-83], 67% women), median daily MME was 60 mg (3-840), and median opioid therapy duration was 60 months (3-360). Abnormal case detection testing was found in 11 (10.8%) patients, and diagnosis of OIAI was made in 9 (9%). Patients with OIAI were on a higher daily MME (median, 140 [20-392] mg vs 57 [3-840] mg, P = 0.1), and demonstrated a 4 times higher cumulative opioid exposure (median of 13,440 vs 3120 mg*months, P = 0.03). No patient taking &lt;MME of 20 mg/day developed OIAI (sensitivity of 100% for MME &gt; 20 mg); however, specificity of MME cutoff &gt;20 mg was only 19%. After opioid discontinuation, 6/7 patients recovered adrenal function. Conclusion The prevalence of OIAI was 9%, with MME cumulative exposure being the only predictor for OIAI development. Patients on MME of 20 mg/day and above should be monitored for OIAI.