Patients with cirrhosis who have coronary artery disease treated with cardiac stents have high rates of gastrointestinal bleeding, but no increased mortality.

BACKGROUND: Patients with coronary artery disease (CAD) treated with stents require dual antiplatelet therapy (DAPT). For cirrhotics, who often have varices and coagulopathy, it is not clear if the risk of gastrointestinal bleeding (GIB) should preclude use of DAPT. AIM: To compare GIB and mortality rates in cirrhotics with CAD treated medically or with stents. METHODS: Using institutional databases, we identified patients with cirrhosis and CAD treated with stents or medical therapy between January 2000-September 2015. Primary outcomes were GIB and mortality. RESULTS: We identified 148 cirrhotics with CAD; 68 received stents (cases), 80 were treated with medical therapy (controls). Cases and controls had similar demographics, comorbidities, MELD scores and clinical presentation; DAPT was used in 98.5% of cases vs 5% of controls. The incidence of GIB was significantly higher in cases than controls (22.1% vs 5% at 1 year, P=.003; 27.9% vs 5% at 2 years, P=.0002), whereas all-cause mortality was similar (20.6% vs 21.3%). No patient required surgery or angiography for GIB, and no known patients died due to GIB. Multivariate analysis revealed use of a proton pump inhibitor (PPI) was highly protective against GIB (OR=0.26, 95%CI=0.08-0.79). CONCLUSIONS: CAD treatment with stents in our cirrhotics was associated with a significantly increased risk of GIB, but no adverse effects on survival. Although it remains unclear whether the cardiovascular benefits of stents outweigh the GIB risk, our findings suggest that DAPT should not be withheld from stented cirrhotics for fear of GIB. Moreover, the use of a PPI should be strongly considered.

The effects of homelessness on Veterans' health care service use: an evaluation of independence from comorbidities.

OBJECTIVES: This study evaluates the prevalence of Multiple Comorbid Chronic Disease (MCCD) within homeless and non-homeless Veterans and the association between MCCD and inpatient medical care. METHODS: All individuals seen in the VA North Texas Health Care System between October 1, 2009 and September 30, 2010 (n = 102,034) were evaluated. Homelessness during the year and the number of common chronic diseases were evaluated for an association with likelihood of medical and psychiatric hospitalizations, bed days of care, inpatient substance treatment, rehabilitation admissions, and emergency department visits. RESULTS: Homeless Veterans had higher all-cause mortality rates and rates of use of almost all resources after controlling for chronic disease burden using the Charlson Comorbidity Index, psychiatric illnesses, substance use disorders, and demographic variables. CONCLUSIONS: Homelessness Veterans are vulnerable to a high use of resources and mortality, independent of medical and psychiatric conditions. This finding should focus additional attention on reducing homelessness.

An EGFR wild type-EGFRvIII-HB-EGF feed-forward loop regulates the activation of EGFRvIII.

EGFRvIII is a key oncogene in glioblastoma (GBM). EGFRvIII results from an in-frame deletion in the extracellular domain of EGFR, does not bind ligand and is thought to be constitutively active. Although EGFRvIII dimerization is known to activate EGFRvIII, the factors that drive EGFRvIII dimerization and activation are not well understood. Here we present a new model of EGFRvIII activation and propose that oncogenic activation of EGFRvIII in glioma cells is driven by co-expressed activated EGFR wild type (EGFRwt). Increasing EGFRwt leads to a striking increase in EGFRvIII tyrosine phosphorylation and activation while silencing EGFRwt inhibits EGFRvIII activation. Both the dimerization arm and the kinase activity of EGFRwt are required for EGFRvIII activation. EGFRwt activates EGFRvIII by facilitating EGFRvIII dimerization. We have previously identified HB-EGF, a ligand for EGFRwt, as a gene induced specifically by EGFRvIII. In this study, we show that HB-EGF is induced by EGFRvIII only when EGFRwt is present. Remarkably, altering HB-EGF recapitulates the effect of EGFRwt on EGFRvIII activation. Thus, increasing HB-EGF leads to a striking increase in EGFRvIII tyrosine phosphorylation while silencing HB-EGF attenuates EGFRvIII phosphorylation, suggesting that an EGFRvIII-HB-EGF-EGFRwt feed-forward loop regulates EGFRvIII activation. Silencing EGFRwt or HB-EGF leads to a striking inhibition of EGFRvIII-induced tumorigenicity, while increasing EGFRwt or HB-EGF levels resulted in accelerated EGFRvIII-mediated oncogenicity in an orthotopic mouse model. Furthermore, we demonstrate the existence of this loop in human GBM. Thus, our data demonstrate that oncogenic activation of EGFRvIII in GBM is likely maintained by a continuous EGFRwt-EGFRvIII-HB-EGF loop, potentially an attractive target for therapeutic intervention.

High rates of stopping or switching biological medications in veterans with rheumatoid arthritis.

OBJECTIVES: To define the characteristics of a population of veterans with rheumatoid arthritis (RA) who have stopped or switched their first biologic agent, and to assess if measures of disease activity are predictors in the decision to alter the regimen. METHODS: A retrospective analysis of the VA electronic medical record system identified RA patient demographic and disease activity parameters from 1999 to 2007. Demographic data included age, race/ethnicity, sex, and tobacco use. Disease-specific data included date of RA onset, past DMARD therapies, prednisone use, as well as the disease activity score (DAS-28) and the health assessment questionnaire (HAQ) at each clinic visit. The use of six biologicals (infliximab, etanercept, adalimumab, abatacept, rituximab, anakinra) was identified in order to compare those who continued with the medication to those discontinuing or switching to another biological. Descriptive and parametric statistics were applied to define differences between the two groups. RESULTS: Of 454 RA patients identified, 212 have been on a biologic agent at one point in time, and 100 patients (47%) had either stopped or switched their first biologic agent. Among these 100 patients, the most common reasons for stopping or switching a biologic agent were adverse events (in 48%) and inefficacy (43%) Adverse events included malignancies (23% of 48 patients), rash (23%), infections (18.8%), and cardiac complications (18.8%). When comparing the 100 patients versus the 112 that did not stop or switch their first agent, the DAS-28 correlated significantly with a change of regimen with an OR 2.1 (p<0.001). The HAQ score had an OR of 2.0 (p<0.04). CONCLUSION: RA patients who continue taking their initial biologic medication have similar age, RA disease duration, ethnicity, and smoking status to those requiring switching or discontinuation. The DAS28 and HAQ scores significantly correlated with stopping or switching of a first biologic agent. Adverse event rates were high and their distributions differed in this population compared to previous studies of younger Caucasian females.

Expectancy variables predicting tolerance and avoidance of pain in chronic pain patients.

Previous research on anxiety and some recent reports on chronic pain suggest that the response to aversive stimuli may be influenced by expectations rather than actual experience. This study examined the contributions of four expectancy-related variables to the tolerance and avoidance of pain: pain expectancy, response expectancy, self-efficacy expectancy, and danger expectancy. Chronic pain sufferers volunteered to undergo cold pressor pain on two trials (the first for practice, and the second to determine tolerance) and then faced the prospect of a third trial (to determine avoidance). It was found that expected tolerance (or response expectancy) significantly predicted actual tolerance, whereas expected danger significantly predicted avoidance. These findings are in partial agreement with previous research. Among the clinical implications are that chronic pain sufferers generally associate pain with damage and they predict their pain tolerance well; they do not necessarily escape from a compulsory activity that produces pain, but given the chance they would rather avoid it in the first place.