Novel multi-marker proteomics in phenotypically matched patients with ST-segment myocardial infarction: association with clinical outcomes

Journal of Thrombosis and Thrombolysis - Early prediction of significant morbidity or mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) represents an unmet...     

Temporal changes in biomarkers and their relationships to reperfusion and to clinical outcomes among patients with ST segment elevation myocardial infarction

Coronary plaque rupture mediating acute ST segment elevation myocardial infarction (STEMI) is associated with a systemic inflammatory response. Whether early temporal changes in inflammatory biomarkers are associated with angiographic and electrocardiographic markers of reperfusion and subsequent clinical outcomes is unclear. In the APEX-AMI biomarker substudy, 376 patients with STEMI had inflammatory biomarkers measured at the time of hospital presentation and 24 h later. The primary outcome was the 90-day composite of death, shock, or heart failure. Secondary reperfusion outcomes were (1) worst least residual ST segment elevation (ST-E: <1 mm, 1 to <2 mm, ≥2 mm) and (2) post-percutaneous coronary intervention (PCI) TIMI flow grade (0/1/2 vs 3) and TIMI myocardial perfusion grade (TMPG 0/1 vs 2/3). The 90-day incidence of death, shock or heart failure was 21.3 % in this cohort. Electrocardiographic reperfusion (worst residual ST-E <1 mm, 1 to <2 mm, ≥2 mm) was associated with differences in 24 h change in N-terminal proB-type natriuretic peptide (NT-proBNP) (1192.8, 1332.5, 1859.0 ng/mL; p = 0.043) and the pro-inflammatory cytokines Interleukin (IL)-6 (14.0, 13.6, 22.1 pg/mL; p = 0.016), IL-12 (?0.5, ?0.9, ?0.1 pg/mL; p = 0.013), and tumor necrosis factor α (TNFα) (1.0, 0.6, 3.6 pg/mL; p = 0.023). Angiographic reperfusion (TMPG 0/1 vs 2/3) was associated with changes in median NT-proBNP (2649.3, 1382.7 ng/mL; p = 0.002) and IL-6 (28.7, 15.1; p = 0.040). After adjustment for baseline covariates, the 24 h change in the pro-inflammatory cytokine TNFα [hazard ratio (HR) 0.49; 95 % CI 0.26–0.95; p = 0.035] and the anti-inflammatory cytokine IL 10 (HR 1.41; 95 % CI 1.06–1.87; p = 0.018) were independently associated with the primary composite outcome. Successful coronary reperfusion was associated with less systemic inflammatory response and greater temporal inflammatory changes were independently associated with higher 90-day composite of death, shock, or heart failure. These findings provide support for an association between success of reperfusion, an acute STEMI inflammatory response and subsequent clinical outcomes.     

Mental distress in medical students of Addis Ababa University

Life in medical schools is said to be stressful leading to emotional distress. A study was conducted to estimate the prevalence of mental distress among medical students of Addis Ababa University using a Self Report Questionnaire (SRQ) in 2001. The SRQ was distributed to the entire student population through class representatives. A total of 273 (80%) students returned completed questionnaires. Of these, 83.2% were males and over 85% were above the age of 20 years. About 70% were Orthodox Christians and nearly half of the study population was from Addis Ababa. The one month prevalence of mental distress was found to be 32.6%. Over 6.0% reported that they had suicidal ideation in the last one month. Females reported symptoms of mental distress more often than males, but the difference was not statistically significant (X2 =2.97, df= 1, P=0.08). Age and level of training were shown to have significant association with mental distress (Age, X2=20.88, df=2, p<0.001 and year of study, X2 = 32.04, df=4, p<0.001). Those who were 20 years of age or below and those who were in the preclinical years of training were likely to report symptoms of mental distress more often than those who were older and above preclinical years of training, respectively. Students who use substances reported symptoms of mental distress more often than non users, but the difference was not statistically significant. The study showed that the risk of mental distress decreases as year of study advances in the medical school. However, this trend showed deflection in the year of internship. This study showed that mental distress is a common problem among medical students of Addis Ababa University. Further studies and support services for the students are recommended.     

Risk Model and Nomogram for Dysphagia and Xerostomia Prediction in Head and Neck Cancer Patients Treated by Radiotherapy and/or Chemotherapy

In our randomized trial on hyperbaric oxygen (HBO), it was shown that HBO could reduce dysphagia and xerostomia, which are frequently encountered after (chemo-) radiotherapy (RT) and/or surgery for head and neck cancer (HNC). A risk model and nomogram are developed to select those patients who most likely will respond to HBO treatment. A total of 434 HNC patients treated from 2000 to 2008 were analyzed and filled out the EORTC QLQC-30 and H&N35 questionnaires. Age, gender, chemotherapy, T and N stages, site, radiotherapy technique, RT boost, surgery of the primary tumor and neck, bilateral RT, and dose were analyzed in a statistical model. The discriminative value of the model was evaluated based on receiver operating characteristics (ROC), the area under the curve (AUC), sensitivity, specificity, and proportion of correctly classified measures. Significant factors in predicting swallowing problems are age, follow-up duration, tumor site, chemotherapy, surgery of the primary tumor and neck, and dose. For dry mouth, the significant factors are age, gender, tumor site, N stage, chemotherapy, and bilateral irradiation. For dysphagia and xerostomia, the area under the ROC curve is 0.7034 and 0.7224, respectively, with a specificity of 89/77 %, sensitivity of 27/58 %, and a positive predictive value of 83/67 % for dysphagia and xerostomia, respectively. The developed predictive risk model could be used to select patients for costly hyperbaric oxygen treatment to prevent or reduce severe late side effects of HNC treatment. Our model serves as a guideline for the Department of Radiation Oncology to reduce costs by excluding patients not amenable to hyperbaric oxygen protocols. The nomogram presented is a useful tool for clinicians in assessing patient risks when deciding on follow-up strategies (e.g., hyperbaric oxygen treatment) after RT or surgery for HNC.     

Genome-wide association study (GWAS)-identified disease risk alleles do not compromise human longevity

A set of currently known alleles increasing the risk for coronary artery disease, cancer, and type 2 diabetes as identified by genome-wide association studies was tested for compatibility with human longevity. Here, we show that nonagenarian siblings from long-lived families and singletons older than 85 y of age from the general population carry the same number of disease risk alleles as young controls. Longevity in this study population is not compromised by the cumulative effect of this set of risk alleles for common disease.