The Importance of Immunohistochemical Heterogeneous Expression of MMR Protein in Patients with Colorectal Cancer in Stage II and III of the Disease.

Background and objectives: In patients with colorectal cancer (CRC), heterogeneous expression of Mismatch repair (MMR) proteins can manifest itself in several different forms and is not such a rare phenomenon. Therefore, it is very important to recognize the nuclear expression of MMR proteins of different MMR status in order to avoid false positive or false negative results. The aim of this study was to determine the frequency and distribution of heterogeneous expression of MMR proteins in patients with stages II and III of the disease as well as its association with clinical, demographic and pathological characteristics of CRC in relation to proficient and deficient expression of MMR proteins. Material and Methods: The study included 104 cases of colorectal cancer obtained from surgical colectomy material in stages II and III of the disease. Results: From a total of 104 patients with colorectal cancer, immunohistochemical analysis of the expression of all four MMR proteins showed that heterogeneous expression of MMR proteins (as well as deficient immunoreactivity of tumor cells) was present in 12 cases, while proficient expression of MMR proteins was detected in 80 tumors. Conclusions: Our study showed that the only independent predictors of the loss of MMR protein expression were younger patient age and right-sided anatomical location of the tumor. The study also established the existence of heterogeneous expression of MMR proteins in a non-negligible percentage of CRCs (11.5%), where heterogeneous nuclear expression of MMR proteins was described in several different forms.

Diagnosis and treatment of angiographically unclear coronary lesions.

Although selective coronary angiography is the gold standard diagnostic technique for coronary lesions, this method does not provide all information regarding pathophysiologic mechanisms. We herein describe a patient in their early 60s with a 3-month history of pronounced angina. Coronary angiography revealed a central line of illumination in the proximomedial segment of the right coronary artery, suggesting a chronic coronary dissection/recanalized thrombus, along with positive remodeling and TIMI grade 2 flow. Optical coherence tomography showed a recanalized thrombus and multiple lumens separated by thin septa. Because of the significantly reduced flow and signs of ischemia in the right coronary artery irrigation territory, we decided to perform percutaneous coronary intervention. Post-treatment optical coherence tomography indicated optimal apposition and expansion of the stents with positive remodeling of the blood vessel. We believe that decisions regarding treatment modalities should be guided by the presence or absence of ischemia. Lesions that are causing myocardial ischemia should be revascularized; otherwise, medical treatment can be utilized.

The timing of death in acute pulmonary embolism patients regarding the mortality risk stratification at admission to the hospital.

Background: The management of patients with acute pulmonary embolism (aPE) depends on the severity of aPE. The timing of death in various aPE risk subgroups is only partially known. Methods: 1618 patients with an objectively established aPE diagnosis with computed tomography pulmonary angiography enrolled in the regional PE registry were included in the study. According to ESC criteria, patients were stratified at admission to the hospital in four risk strata. The timing of PE-related and non-PE-related deaths was analyzed regarding mortality risk. Results: PE-related, and non-PE-related hospital death rates were 1.1 % and 1.5 % in low, 1.1 % and 4.8 % in intermediate-low, 8.1 % and 5.9 % in intermediate-high, and 27.7 % and 6.9 % in high-risk groups, respectively. The median time of PE-related and non-PE-related death across the PE mortality risk were: 4 (1.7-7.5) and 7.0 (4-14.7) days in low, 1.5 (1.0-9.5) and 11.5 (2.0-21.0) days in intermediate-low, 4.0 (2.0-9.0) and 9.0 (5.7-18.2) days in intermediate-high, 2.0 (1.0-4.75) and 7.0 (3.0-21.2) days in high-risk subgroups. 48.2 % and 17.1 % of patients who died in the high and intermediate-high risks died during the first hospital day. After the 6th hospitalization day, PE-related deaths were recorded in 43.9 % of deaths from intermediate-high and 17.9 % from high-risk subgroups. Conclusion: PE-related mortality is prominent on the first hospitalization day in high and intermediate-high-risk PE. A substantial proportion of intermediate-high and high-risk patient's PE deaths occurred after the first 6 days of hospitalization.

Temporal analysis of non-ST segment elevation-acute coronary syndrome (NSTEACS) outcomes in 'young' patients under the age of fifty: A nationwide cohort study.

BACKGROUND: The characteristics and risk factor profile of young patients presenting with non-ST segment elevation acute coronary syndrome (NSTEACS) and how they may have changed over time is not well reported. METHODS: We identified 26,708 NSTEACS patients aged under 50 presenting to United Kingdom (UK) hospitals between 2010 and 2017 from Myocardial Ischaemia National Audit Project (MINAP). We calculated incidence of NSTEACS per 100,000 UK population, using Office of National Statistics (ONS) population estimates, prevalence of comorbidities, ethnicity, and in-hospital mortality. We formed biennial groups to enable comparison, 2010-2011, 2012-2013, 2014-2015 and 2016-2017. RESULTS: The incidence of NSTEACS per 100,000 population showed minimal change between 2010 and 2017 (2010: 5.4 per 100,000 and 2017; 4.9 per 100,000). Rates of smoking (2010-11; 58% and 2016-17; 53%), and family history of coronary artery disease (CAD) (2010-11; 51% and 2016-17; 44%) fell, but the proportion of patients from an ethnic minority background (2010-11; 12% and 2016-17; 20%), with diabetes mellitus (DM) (2010-11; 14%, and 2016-17; 18%) and female patients (2010-11; 22% and 2016-17; 24%) increased over the study period. Mortality from NSTEACS remained unchanged (2010-11; 1% and 2016-17; 1%). CONCLUSIONS: The incidence of NSTEACS in patients aged under fifty has not reduced despite reduction in prevalence of risk factors such as smoking hypercholesterolaemia in those admitted to UK hospitals. Despite improved rates of early invasive coronary angiography and percutaneous coronary intervention in 'young' NSTEACS patients, in-hospital mortality remains unchanged.

Signs and symptoms of acute pulmonary embolism and their predictive value for all-cause hospital death in respect of severity of the disease, age, sex and body mass index: retrospective analysis of the Regional PE Registry (REPER).

BACKGROUND: The incidence of the signs and symptoms of acute pulmonary embolism (PE) according to mortality risk, age and sex has been partly explored. PATIENTS AND METHODS: A total of 1242 patients diagnosed with acute PE and included in the Regional Pulmonary Embolism Registry were enrolled in the study. Patients were classified as low risk, intermediate risk or high risk according to the European Society of Cardiology mortality risk model. The incidence of the signs and symptoms of acute PE at presentation with respect to sex, age, and PE severity was investigated. RESULTS: The incidence of haemoptysis was higher in younger men with intermediate-risk (11.7% vs 7.5% vs 5.9% vs 2.3%; p=0.01) and high-risk PE (13.8% vs 2.5% vs 0.0% vs 3.1%; p=0.031) than in older men and women. The frequency of symptomatic deep vein thrombosis was not significantly different between subgroups. Older women with low-risk PE presented with chest pain less commonly (35.8% vs 55.8% vs 48.8% vs 51.9%, respectively; p=0.023) than men and younger women. However, younger women had a higher incidence of chest pain in the lower-risk PE group than in the intermediate-risk and high-risk PE subgroups (51.9%, 31.4% and 27.8%, respectively; p=0.001). The incidence of dyspnoea (except in older men), syncope and tachycardia increased with the risk of PE in all subgroups (p<0.01). In the low-risk PE group, syncope was present more often in older men and women than in younger patients (15.5% vs 11.3% vs 4.5% vs 4.5%; p=0.009). The incidence of pneumonia was higher in younger men with low-risk PE (31.8% vs<16% in the other subgroups, p<0.001). CONCLUSION: Haemoptysis and pneumonia are prominent features of acute PE in younger men, whereas older patients more frequently have syncope with low-risk PE. Dyspnoea, syncope and tachycardia are symptoms of high-risk PE irrespective of sex and age.

Association of Blood Leukocytes and Hemoglobin with Hospital Mortality in Acute Pulmonary Embolism.

This study aimed to assess the prognostic significance of total leukocyte count (TLC) and hemoglobin (Hb) levels upon admission for patients with acute pulmonary embolism (PE), considering the European Society of Cardiology (ESC) model for mortality risk. 1622 patients from a regional PE registry were included. Decision tree statistics were employed to evaluate the prognostic value of TLC and Hb, both independently and in conjunction with the ESC model. The results indicated all-cause and PE-related in-hospital mortality rates of 10.7% and 6.5%, respectively. Subgrouping patients based on TLC cut-off values (≤11.2, 11.2-16.84, >16.84 × 109/L) revealed increasing all-cause mortality risks (7.0%, 11.8%, 30.2%). Incorporating Hb levels (≤126 g/L or above) further stratified the lowest risk group into two strata with all-cause mortality rates of 10.1% and 4.7%. Similar trends were observed for PE-related mortality. Notably, TLC improved risk assessment for intermediate-high-risk patients within the ESC model, while Hb levels enhanced mortality risk stratification for lower-risk PE patients in the ESC model for all-cause mortality. In conclusion, TLC and Hb levels upon admission can refine the ESC model's mortality risk classification for patients with acute PE, providing valuable insights for improved patient management.

New-Onset Paroxysmal Atrial Fibrillation in the Setting of Acute Pulmonary Embolism Is Associated with All-Cause Hospital Mortality in Women but Not in Men.

BACKGROUND: Patients with acute pulmonary embolism (PE) may have various types of atrial fibrillation (AF). The role of AF in hemodynamic states and outcomes may differ between men and women. METHODS: In total, 1600 patients (743 males and 857 females) with acute PE were enrolled in this study. The severity of PE was assessed using the European Society of Cardiology (ESC) mortality risk model. Patients were allocated into three groups according to their electrocardiography recordings taken during hospitalization: sinus rhythm, new-onset paroxysmal AF, and persistent/permanent AF. The association between the types of AF and all-cause hospital mortality was tested using regression models and net reclassification index (NRI) and integrated discrimination index (IDI) statistics with respect to sex. RESULTS: There were no differences between the frequencies of the types of AF between men and women: 8.1% vs. 9.1% and 7.5% vs. 7.5% (p = 0.766) for paroxysmal and persistent/permanent AF, respectively. We found that the rates of paroxysmal AF significantly increased across the mortality risk strata in both sexes. Among the types of AF, the presence of paroxysmal AF had a predictive value for all-cause hospital mortality independent of mortality risk and age in women only (adjusted HR, 2.072; 95% CI, 1.274-3.371; p = 0.003). Adding paroxysmal AF to the ESC risk model did not improve the reclassification of patient risk for the prediction of all-cause mortality, but instead enhanced the discriminative power of the existing model in women only (NRI, not significant; IDI, 0.022 (95% CI, 0.004-0.063); p = 0.013). CONCLUSION: The occurrence of paroxysmal AF in female patients with acute PE has predictive value for all-cause hospital mortality independent of age and mortality risk.

Predictive value of admission glycemia in diabetics with pulmonary embolism compared to non-diabetic patients.

AIMS: To examine the relationship between admission glucose (AG) level and short-term in-hospital mortality and to investigate the association between hyperglycemia and major bleeding in PE patients with and without DMT2. METHODS: We evaluated 1165 patients with diagnosed acute PE with multi-detector computed tomography pulmonary angiography (MDCT-PA) enrolled in the Regional multicenter PE registry (REPER). The study population was classified to patients with diabetes mellitus type 2 (DMT2) and those without diabetes. According to quartiles of AG patients, both groups separately were categorized into four subgroups (DMT2 I: < 7.5 mmol/L; II: 7.5-10.0 mmol/L; III: 10.0-15.7 mmol/L; IV: > 15.7 mmol/L and (non-DMT2 I: < 5.5 mmol/L; II: 5.5-6.3 mmol/L; III: 6.3-7.9 mmol/L; IV: > 7.9 mmol/L). RESULTS: All-cause mortality was higher in the DMT2 group (9.5% vs. 18.2%, p < 0.001), and PE-cause mortality was 6% for the patients without DMT2 and 12.4% for DMT2 patients (p = 0.02). The patients in the fourth AG quartiles in both groups, without DMT2 and with DMT2, had significantly higher all-cause and PE-cause in-hospital mortality compared with the first quartile. Rates of major bleeding were similar between the groups. On the multivariable analysis, after adjusting for age, gender and mortality risk, the adherence in the fourth AG quartile had an independent predictive value for all-cause death (HR 2.476, 95% CI 1.017-6.027) only in DM patients. CONCLUSION: In our cohort of patients with acute PE, diabetes was associated with increased rates for all-cause and PE-cause mortality.

Biomarkers for the prediction of early pulmonary embolism related mortality in spontaneous and provoked thrombotic disease.

Factors associated with provoked PE may influence a biomarker's predictive value for the primary outcome. The aim of this study was to investigate the value of BNP, cTnI, CRP and D-Dimer measurements taken soon after hospital admission for the prediction of 30-day PE-caused death in patients with spontaneous versus provoked PE.Data were extracted from a pool of 726 consecutive PE patients enrolled in the multicenter Serbian PE registry. Blood concentrations of BNP, cTnI, CRP and D-dimer were measured during the first 24 h of hospitalization. BNP blood level had strong predictive value for the primary outcome in spontaneous PE (c-statistics 0.943, 95% CI 0.882-1.000, p = .001) and a slightly lower predictive outcome in provoked PE (c-statistics 0.824, 95% CI 0.745-0.902, p < .001). NRI and IDI showed that none of the markers, when added to BNP, could improve Cox regression prediction models for 30-day PE-related mortality in either the spontaneous or provoked PE group. Blood levels of BNP measured during the first 24 h of hospital admission had an excellent predictive value for 30-day PE-related mortality in spontaneous PE and slightly lower predictive value in provoked PE, whereas CRP, cTnI and D-Dimer did not contribute significantly to the predictive value of BNP in either group.

Changes in platelets and anticoagulant protein activity during adenosine-exercise single-photon emission computed tomography stress test.

INTRODUCTION: Activation of haemostasis during physical stress or during myocardial ischemia could be an important mechanism to trigger coronary and stent thrombosis. We examined changes in haemostatic parameters and its association with myocardial ischemia during adenosine-exercise-SPECT (adeno-EX) stress test in coronary patients at least 4 months after coronary stenting. OBJECTIVE: The aim of this study was to examine relationship between changes in haemostatic parameters and stress induced myocardial ischemia quantified by perfusion scintigraphy in stented coronary patients. METHODS: Thirty-seven patients on dual antiplatelet therapy (26 on clopidogrel plus aspirin and 11 on aspirin only) 4-8 months after successful intracoronary stent implantation were enrolled in the study. We determined the levels of platelet aggregability (PA) on ADP (PA-ADP) and epinephrine (PA-EPI), beta-thromboglobulin, platelet factor-4, protein C (PC) and antithrombin (AT) before and 15 minutes after intravenous injection of 150 micro/kg adenosine for4 minutes concomitant with supine ergo-bicycle exercise test for 50 W. The size of stress perfusion defect was measured 15 minutes after stress and in rest 4 hours later by 99mTc-tetrofosmin single photon emission computed tomography (SPECT) within 17 myocardial segments. RESULTS: There were no differences between haemostatic parameters before and after stress. A significant myocardial ischemia after exercise was registered in 12 patients on combined antiaggregation therapy and in 5 patients on aspirin. In this preliminary report, because of a small number of patients in the aspirin group we did not analyse difference in the levels of haemostatic markers and their correlations with the size of perfusion defect. The only significant difference between measured haemostatic parameters in the patients with stress induced ischemia compared to the patients without it, was a lower level of AT activity after stress (81.0% vs. 87.5%; p = 0.027). Antithrombin activity before stress had significant negative correlation with the size of perfusion defect in rest (R2 = 0.219; p = 0.016) and PC activity before stress had significant linear correlation with stress perfusion defect (R2 = 0.248; p = 0.010). CONCLUSION: Baseline activities of natural anticoagulant proteins AT and PC are associated with the size of myocardial perfusion defect during adeno-EX-SPECT test. Patients with significant stress-induced ischemia had lower levels of AT activity after stress.

[Prognostic significance of sinus deceleration during dobutamine stress echocardiography test following acute myocardial infarction].

BACKGROUND/AIM: Chronotropic incompetence during exercise stress testing after acute myocardial infarction is an indicator of ischemia or impaired left ventricular function. On the other side, infusion of dobutamine leads to a typical dose-dependent increase in heart rate. The aim of this study was to evaluate of paradoxical sinus deceleration during dobutamine stress echocardiography (DSE), as the sign of ischemia and impaired left ventricular function, or the consequence of infarction localization, and the estimation of prognostic significance after acute myocardial infarction. METHODS: Our investigation comprised 81 patients hospitalized because of the acute myocardial infarction, and all of them had uncomplicated infarction. Fifty five patients were treated with thrombolytic therapy (67.9%); 53 patients (65.4%) had anterior myocardial infarction, and 28 patients (34.6%) had inferoposterior localization of myocardial infarction. After 10-12 days all of them underwent dobutamine stress echocardiography examination. During the next 3-6 months, the patients underwent coronary angiography. The average follow-up period was 36 +/- 22 months. RESULTS: A decrease in heart rate occurred at the dobutamine doses increasing from 15-40mcg/kg/min in 9 (11.1%) of the patients, in 1 patient with an anterior localization and in 8 patients with an inferoposterior localization. The decrease was sudden in 4 (44.4%), and gradual in 5 (55.6%) of the patients. In 3 patients (33.3%) junction rhythm was developed, and in 2 patients (22.2%) AV block II-III. Only in 2 of them, there was a worsening of regional function during a high dose dobutamine infusion, but 7 of them showed an improvement during a low dose. In 7 (77.8%) of the patients there was a simultaneous decrease in blood pressure. Coronary angiographic examination showed that in 4 (44.4%) of the patients there was a significant coronary artery disease and they underwent the revascularisation procedure. During the follow up period, there was not any significant arrhythmic disorder in that group of the patients or repeated hospitalization because of postinfarction angina, re-infarction, or heart failure. CONCLUSION: We could conclude that paradoxical sinus deceleration is not only an indicator of a significant coronary artery disease and "bad left ventricle". It also may occur as a consequence of vasodepressor reflex (Bezold-Jarisch), even after acute myocardial infarction, withont influencing a long-term prognosis.

Prevention of pocket related complications with fibrin sealant in patients undergoing pacemaker implantation who are receiving anticoagulant treatment.

AIM: The aim of our study was to establish the efficiency of fibrin sealant in the prevention of pocket related complications in patients undergoing pacemaker implantation who are receiving anticoagulant treatment. METHODS: The study was performed on 40 and 41 patients prospectively randomized into treatment and control groups who underwent pacemaker implantation procedure between January 2002 and July 2004 at the Pacemaker Center - Clinical Centre Nis, Serbia. Both groups of patients were receiving anticoagulant treatment with either heparin or warfarin. Surgical procedures between the groups differed only in the application of fibrin sealant prior to wound closure in the treatment group. RESULTS: In the treatment group, there were no pocket related complications while in the control group six patients (14.63%) had minor haematomas that required no treatment. Four patients (9.76%) had significant haematomas (two patients were treated conservatively while the other two needed reintervention). The INR in the treatment group was 2.76+/-0.85 and in the control group 2.65+/-0.79 (P=ns). In the follow-up period (2-27 months) no late complications were registered in either group. CONCLUSION: Fibrin sealant is an effective haemostatic agent. The results obtained in our study show that the administration of fibrin sealant in patients receiving anticoagulant treatment eliminates postoperative haematomas after pacemaker implantation.