Denise Donaldson

This study, a retrospective review of 165 patients with myasthenia gravis, compares the course of the disease for patients with onset before 50 and at or after 50. There were no significant differences between age groups for presenting symptoms, but more of the older patients had progressed to severe disease. More of the younger than the older patients were in remission or were asymptomatic on medication at the last visit. Sixty-two percent of those treated with steroids developed complications, with a larger portion of these being in the older group. Cataracts, infection, and bone changes were particularly significant for the older population. Complications of azathioprine treatment and plasmapheresis were less common. Thymoma was more common in the older population; these patients did no worse than the population as a whole. Sixty-five percent of our patients have undergone thymectomy, most by a modified transsternal approach. A much larger portion of those who underwent thymectomy were in remission at the last visit than those who did not.

BACKGROUND: Urologic experience in heart transplant recipients as a population group has not been reported. METHODS: We reviewed the charts of 48 consecutive heart transplant recipients who were evaluated and treated in our outpatient urologic clinic. Patients were treated for various urologic conditions by both medical and surgical means. RESULTS: No major complications were encountered. CONCLUSIONS: Heart transplant recipients may be treated with minimal morbidity; thus, their urologic complaints should be addressed and treated with confidence.

Background: Macrophages play a central role in atherosclerotic plaque formation. The CC chemokine receptor 2 (CCR2), expressed on the surface of circulating monocytes, and its ligand MCP-1 (CCL2), are present in atherosclerotic plaques and may play a critical part in endothelial monocyte recruitment and activation. MLN1202 is a humanized monoclonal antibody with high specificity to CCR2, which interrupts MCP-1 binding to CCR2. MLN1202 is being developed for the treatment of immune mediated diseases. Hypothesis: We tested the hypothesis that MLN1202 significantly influences disease activity in patients at risk for ASCVD as measured by a reduction in circulating levels of high sensitivity C-reactive protein (hsCRP), an established biomarker of inflammation. Trial Design: In this double-blind placebo controlled study patients with at least 2 or more risk factors for ASCVD, no history or symptoms of ASCVD disease, and circulating levels of hsCRP > 3mg/L, were randomized 1:1 to receive a single infusion of 10 mg/kg MLN1202 (n 56) or placebo (n = 56). Subjects with hypercholesterolemia on stable doses of lipid-lowering agents were included. Circulating levels of hsCRP were determined every 2 weeks, and clinical examination performed every 4 weeks for 16 weeks following treatment. Results and Conclusion: Patients were recruited from nine centers in the US. The study population had a mean age of 60.9 years and included subjects with hypertension (59%), hypercholesterolemia (70%), significant smoking history (28%), and type 2 diabetes (16%). At screening the median value CRP was 6.8 mg/L with interquartile range from 4.7–9.3 mg/L. PK/PD results showed that the plasma level of MLN1202 required for > 90% receptor saturation was maintained for 6 to 8 weeks. A between-group difference in reduction of hsCRP was statistically significant from week 4 through week 8 following dosing. The maximum difference in absolute median reduction was observed at week 8 and it was 1.6 mg/L (p = 0.0275; Wilcoxon); the observed median percent reduction of hsCRP was 24.2% for MLN1202 group versus 2.5% increase for placebo group at 8 weeks (p = 0.0089; Wilcoxon). These data indicate that blockade of CCR2 reduces a biomarker related to inflammation in patients at risk for ASCVD.

Background: Salivary epigenetic biomarkers may detect esophageal cancer. Methods: A total of 256 saliva samples from esophageal adenocarcinoma patients and matched volunteers were analyzed with Illumina EPIC methylation arrays. Three datasets were created, using 64% for discovery, 16% for testing and 20% for validation. Modules of gene-based methylation probes were created using weighted gene coexpression network analysis. Module significance to disease and gene importance to module were determined and a random forest classifier generated using best-scoring gene-related epigenetic probes. A cost-sensitive wrapper algorithm maximized cancer diagnosis. Results: Using age, sex and seven probes, esophageal adenocarcinoma was detected with area under the curve of 0.72 in discovery, 0.73 in testing and 0.75 in validation datasets. Cancer sensitivity was 88% with specificity of 31%. Conclusion: We have demonstrated a potentially clinically viable classifier of esophageal cancer based on saliva methylation.