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Background and objective Elevations in high-sensitivity troponin T (hs-TnT) are frequently observed following extreme physical exercise. In light of this, we sought to determine whether specific clinical characteristics are associated with this phenomenon in patients undergoing cardiac exercise tolerance testing (ETT). Methods We conducted a retrospective analysis of a prospectively collected biospecimen repository of 257 patients undergoing a stress echocardiogram for possible acute coronary syndrome (ACS). Ischemic electrocardiogram (ECG) changes during ETT and the presence or absence of ischemia on imaging were determined by a board-licensed cardiologist. N-terminal pro-brain natriuretic peptide (NT-proBNP) and hs-TnT assays were obtained immediately before and two hours following ETT. We developed linear regression models including several clinical characteristics to predict two-hour stress-delta hs-TnT. Variable selection was performed using the least absolute shrinkage and selection operator (LASSO). Results The mean age of the patients was 52 years [standard deviation (SD): 11.4]; 125 (48.6%) of them were men, and 88 (34.2%) were African-American. Twenty-two patients (8.6%) had ischemia evident on echocardiography, and 31 (12.1%) had ischemic ECG changes during exercise. The mean baseline hs-TnT was 5.6 ng/L (SD: 6.4) and the mean two-hour hs-TnT was 7.1 ng/L (SD: 10.2). Age and ischemic ECG changes were associated with two-hour stress-delta hs-TnT values. Conclusions Based on our findings, ischemic changes in stress ECG and age were associated with an increase in hs-TnT levels following exercise during a stress echo.
RESUMO
BACKGROUND: Multipeptide vaccines for melanoma may cause inflammatory adverse events (IAE). We hypothesize that IAE are associated with a higher rate of immune response (IR) to vaccination and improved clinical outcomes. METHODS: Adult patients with resected, high-risk (stage IIB to IV) melanoma were vaccinated with a combination of 12 class I major histocompatibility complex (MHC)-restricted melanoma epitopes, and IAE were recorded. A separate category for hypopigmentation (vitiligo) was also assessed. CD8(+) T cell IR was assessed by direct interferon gamma ELISpot analysis. Overall survival and disease-free survival were analyzed by Cox proportional hazard modeling. RESULTS: Out of 332 patients, 57 developed IAE, the majority of which were dermatologic (minimum Common Terminology Criteria for Adverse Events [CTCAE] grade 3). Most nondermatologic IAE were CTCAE grade 1 and 2. Vitiligo developed in 23 patients (7 %). A total of 174 patients (53 %) developed a CD8(+) response. Presence of IAE was significantly associated with development of IR (70 vs. 49 %, p = 0.005) and with disease-free survival (hazard ratio 0.54, p = 0.043). There were no significant associations relating vitiligo or IR alone with clinical outcomes. CONCLUSIONS: IAE are associated with a higher rate of CD8(+) T cell response after vaccination therapy for high-risk melanoma. Our findings suggest either that antitumor activity induced by class I MHC-restricted peptide vaccines may depend on immunologic effects beyond simple expansion of CD8(+) T cells or that the intrinsic inflammatory response of patients contributes to clinical outcome in melanoma.