THE PROGNOSTIC UTILITY OF LEUKOCYTE AND PLATELET COUNTS FOR RISK ASSESSMENT OF IN-HOSPITAL COMPLICATIONS IN PATIENTS WITH ACUTE ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION.

OBJECTIVE: The aim: We have aimed to develop method of risk assessment in patients with acute STEMI using blood cells count useful in everyday clinical practice. PATIENTS AND METHODS: Materials and methods: 317 STEMI patients admitted to ICCU starting at 01/2014 to 06/2020 were included in this study. Data were evaluated partially retrospectively (n=214), 1st group) and prospectively, applying new risk-assessment tool in 103 patients 2nd group). Study groups did not differ in terms of all clinical characteristics. RESULTS: Results: To evaluate criteria of severity of in-hospital complication we have created in-hospital complication index (HCI), composed according to number of adverse events per patient. Based on correlation analyses we have composed complex WBC-platelets (WBC-PLT) index = ((GRA - MON) / LYM) · 10 + PDWc + P-LCR). In the 1st study group WBC-PLT index was associated with in-hospital complications' index and correlated with neutrophil-leukocytes ratio (NLR) (p<0,001 and p<0,0005 respectively). WBC-PLT index > 137 appeared to be mildly associated with increased risk of adverse in-hospital outcomes (with specificity of 78 % and low sensitivity of 64 %, AUC- 0,72). Further prospective study of WBC-PLT index measured on the first STEMI-day (group 2) revealed that this parameter was more informative regarding association with adverse in-hospital events whereas NLR had low accuracy in risk assessment. CONCLUSION: Conclusions: WBC-PLT index assessed on the first STEMI day may be used as a tool for detection of patients at risk of adverse in-hospital events in the every-day clinical practice.

IMP3, a proposed novel basal phenotype marker, is commonly overexpressed in adenoid cystic carcinomas but not in apocrine carcinomas of the breast.

Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) is a member of the insulin-like growth factor-II signaling pathway, and has recently been described as a biomarker of basal-like breast carcinomas. This study explored IMP3 expression in adenoid cystic carcinomas of the breast, a special type of basal-like, triple-negative (estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2/neu protein negative) carcinoma and compared it with a group of apocrine carcinomas, which are an example of estrogen receptor/progesterone receptor negative, special type of breast carcinoma. Eighteen breast adenoid cystic carcinomas (16 primary and 2 corresponding metastases) and 18 apocrine carcinomas (16 invasive and 2 in situ) were evaluated for the expression of IMP3 protein using immunohistochemical method. A cut-off value for IMP3 positivity was set at 10%. Thirteen of 16 (81.3%) primary adenoid cystic carcinomas overexpressed IMP3 protein, predominantly in membranous distribution. The mean percentage of positive cells among primary adenoid cystic carcinomas was 50%. Both metastatic adenoid cystic carcinomas also strongly overexpressed IMP3 protein (70% and 80% of the tumor cells, respectively). In contrast, only 4 of 16 invasive apocrine carcinomas (25%) exhibited IMP3 positivity with significantly lower percentage of positive cells (27%, P<0.001). Two in-situ apocrine carcinomas were negative. Our results indicate that IMP3 may be an additional basal-type marker in breast carcinoma whose expression can be occasionally seen in other types of breast carcinomas such as apocrine type.

ER-α36, a novel isoform of ER-α66, is commonly over-expressed in apocrine and adenoid cystic carcinomas of the breast.

BACKGROUND: ER-α36 is a novel 36 kDa isoform of the full-length oestrogen receptor alpha (ER-α66). ER-α36 primarily localises to the cytoplasm and the plasma membrane, and responds to membrane-initiated oestrogen and antioestrogen signalling pathways. AIM: To examine the expression of ER-α36 in apocrine and adenoid cystic carcinoma of the breast, both of which are consistently ER-α66 negative and currently lack effective targeted therapeutic options. METHODS: 19 pure apocrine carcinomas (17 invasive and two in-situ carcinomas) and 11 adenoid cystic carcinomas of the breast were evaluated for ER-α36 expression, along with expressions of ER-α66, progesterone receptor (PR) and androgen receptor (AR) using immunohistochemical methods. RESULTS: All pure apocrine carcinomas showed a characteristic steroid receptor expression profile (ER-α66 and PR negative, AR strongly positive). ER-α36 expression was detected in 18/19 pure apocrine carcinomas (94.7%, 95% CI 75.1 to 98.7) in predominantly membranous and cytoplasmic distribution. When positive, pure apocrine carcinomas uniformly (100% of cells) expressed ER-α36. All adenoid cystic carcinomas were uniformly negative for all three classic steroid receptors, but ER-α36 was detected in 8/11 cases (72.7%, 95% CI 42.8 to 90) with the similar sub-cellular pattern of expression as in the pure apocrine carcinomas. When positive, adenoid cystic carcinomas expressed ER-α36 in the majority of cells (average 76%). CONCLUSION: ER-α36, a novel isoform of ER-α66, is frequently over-expressed in apocrine and adenoid cystic carcinomas of the breast. These results indicate a potential for a novel targeted treatment in these cancers.

Adenoid cystic carcinomas of the breast have low Topo IIα expression but frequently overexpress EGFR protein without EGFR gene amplification.

Adenoid cystic carcinoma of the breast is a rare subtype of breast cancer with basal-like features. Published studies on breast adenoid cystic carcinoma are limited, resulting in relatively scarce information on the value of predictive tumor markers. We studied 20 primary cases of adenoid cystic carcinoma of the breast for expression of estrogen receptor, progesterone receptor, androgen receptor, epidermal growth factor receptor, HER-2/neu, and topoisomerase IIα using immunohistochemistry and fluorescent in situ hybridization methods. Estrogen and progesterone receptor expression were detected in 1 case each. All tumors were uniformly negative for Her-2/neu expression. Androgen receptor and topoisomerase IIα expression were weakly positive in three cases and 7 cases, respectively. Epidermal growth factor receptor overexpression was detected in 13 cases (65% of all cases). Amplification of TOP2A or HER-2/neu gene was not detected in any of the cases. Our study shows that the majority of adenoid cystic carcinomas of the breast do not overexpress Her-2/neu, topoisomerase IIα, or estrogen receptor, and thus, they are unlikely to respond to therapies targeting these proteins. However, these tumors frequently over-express epidermal growth factor receptor, indicating a potential benefit from anti-epidermal growth factor receptor therapy for patients with advanced adenoid cystic carcinomas of the breast.

Treatment and outcomes of eastern Europeans with coronary syndromes in OPUS-TIMI 16.

BACKGROUND: Registries and clinical trials have offered limited evidence on the translation of acute coronary syndrome trial findings into local practices in Eastern Europe. We examined differences in acute coronary syndrome treatment and outcomes between Eastern Europe and other regions in OPUS TIMI-16, a multinational trial of oral glycoprotein IIb/IIIa inhibition for ST-segment and non-ST-segment elevation acute coronary syndromes conducted between 1997 and 1999. METHODS AND RESULTS: We compared variation in baseline characteristics, adjunctive treatment, and outcomes of patients in Eastern Europe and other regions of the world. We found that during this period, Eastern European sites made significantly more use of medications for coronary prevention before and after hospitalization. These sites, however, also made less use of adjunctive medications during their hospitalization. Fewer Eastern European patients received lipid-lowering medication both prior to admission and following discharge. Eastern European patients also underwent fewer percutaneous coronary interventions. Patients in Eastern Europe had worse outcomes at 30 days and at 10 months. CONCLUSION: This study revealed disparities in the use of medical treatments and percutaneous coronary interventions between Eastern European sites and trial sites in other countries. These findings indicate the need for studies to address the sources of treatment and outcome variation. The underuse of effective treatment modalities in all regions calls for strategies to improve access to cardiovascular therapies.

Unfortunate impact of age on the management and outcomes of unstable angina and non-ST elevation myocardial infarction (The GUARANTEE Registry).

Few data are available from the registries on the impact of age and gender on treatment and outcomes of patients admitted for unstable angina and non-ST elevation myocardial infarction (UA/NSTEMI). We examined the clinical characteristics, differences in management and outcomes, associated with age in 2948 consecutive patients with UA/NSTEMI. Prospectively collected data from the Global Unstable Angina Registry and Treatment Evaluation (GUARANTEE) registry were analyzed, comparing patients older than 75 years of age and those 75 years and younger. Patients presenting at a younger age, both men and women, were more likely to have a family history of coronary artery disease, to be current smokers, and to have hypercholesterolemia (P < 0.001). Older patients more commonly had a prior history of stroke, angina, myocardial infarction (MI), and congestive heart failure (P < 0.05), and had more diffuse disease on angiography (P < 0.001). Although older women more often "ruled-in" for MI on admission, they were less likely to be cared for by a cardiologist (P < 0.05). A gradient in the use of cardiac catheterization was seen, with greatest use in younger men, 54.2% versus 47.4% for younger women, 43.1% for older men, and the lowest use in older women, 34.5% (P < 0.01). An opposite gradient of in-hospital mortality was seen, with 0.7%, 0.7%, 0.9%, and 3.2% across the 4 groups, respectively, with older women having worse outcomes (P = 0.008). Unfortunately, a "reverse targeting" of procedures to patient risk was seen among elderly, even when stratified by gender, with older patients being higher risk, but less likely to receive appropriate procedures. To improve the outcomes of elderly men and women with UA/NSTEMI, they should be managed more aggressively.