The impact of earthquakes on the frequency and prognosis of the most common emergency cardiac conditions.

AIM: To assess whether the number of patients with a cardiac chief complaint and their characteristics differed between before and after two major earthquakes that struck Croatia in 2020. METHODS: We collected data on all visits of patients with a cardiac chief complaint examined in the emergency departments of six hospitals nearest to the epicenters. Patients seen during the 7 days before the earthquake were compared with those seen on the day and during the 6 days after the earthquake. RESULTS: Patients seen after the earthquake were younger (68 [59-79] vs 72.5 [65-80]; P<0.001) and less frequently had cardiovascular disease (32.9% vs 42.8%; P<0.001). This group less frequently had the primary diagnosis of acute myocardial infarction (AMI) (15.6% vs 21.9%; P=0.005), heart failure (9.3% vs 19.4%; P<0.001), dysregulated hypertension (13.9% vs 19.4%; P=0.01), but more frequently had non-anginal chest discomfort (28.8% vs 18.0%; P<0.001). In a subgroup analysis of patients seen in hospitals located within 20 km from the epicenter, significantly more patients seen after the earthquake compared with those seen before the earthquake presented with AMI (14.5% vs 22.8%; P=0.028), acute elevation of blood pressure (10% vs 21.8%, P=0.001), and paroxysmal arrhythmias treated with electrocardioversion (0.9% vs 4.5%, P=0.022). CONCLUSION: After two moderately strong earthquakes, hospitals within 20 km from the epicenter saw a significant increase in acute cardiac conditions such as elevated blood pressure, AMI, and cardioverted arrhythmias. Eventually, these earthquakes had no impact on the outcomes of the studied population.

Red Cell Distribution Width in Acute Pulmonary Embolism Patients Improves 30-Day Mortality Risk Stratification Based on the Pulmonary Embolism Severity Index.

PURPOSE: To validate red cell distribution width (RDW) as an improvement in 30-day mortality risk stratification based on the Pulmonary Embolism Severity Index (PESI) in acute pulmonary embolism (PE). PATIENTS AND METHODS: Prospective observational analysis of consecutive adult acute PE patients. RESULTS: Among 731 patients, 30-day mortality was 11.9%. With adjustment for the PESI score and number of covariates, higher RDW was associated with higher mortality (RDW continuous: OR 1.21, 95% CI 1.06-1.38; Bayesian OR 1.22, 1.07-1.40; RDW 'high' [>14.5% in men >16.1% in women] vs normal: OR 3.83, 1.98-7.46; Bayesian OR 3.98, 2.04-7.68]. Crude mortality was 3.6% if PESI 86-105 (intermediate risk), but 1.2% if RDW normal and 7.1% if RDW high; 11.8% if PESI 106-125 (high risk), but 3.6% if RDW normal and 18.8% if RDW high. Adjusted probabilities showed higher mortality (ORs between 3.5-5.8) if RDW was high in any PESI risk subgroup. Crude mortality rates in two random-split subsets (n=365 and n=366) again showed the same patterns. CONCLUSIONS: On-admission RDW above the normal range improves 30-day mortality risk stratification based on PESI score in acute PE. Particularly, it corrects PESI-based intermediate-risk or high-risk allocation by reclassification into very low-risk (<3.5%) or very high-risk (>11.0%).

Patients with dementia and atrial fibrillation less frequently receive direct oral anticoagulants (DOACs) and experience higher thrombotic and mortality risk.

OBJECTIVE: To investigate differences in clinical presentation, anticoagulation pattern and outcomes in patients with dementia and atrial fibrillation (AF). METHODS: A total of 1217 hospitalized patients with non-valvular AF from two institutions were retrospectively evaluated. Diagnosis of dementia was established by a psychiatrist or a neurologist prior to or during hospitalization. Adequacy of warfarin anticoagulation was assessed during follow-up using at least 10 standardized international ratio values. In addition to unmatched comparison, nested case-control study was performed to further evaluate differences in clinical outcomes between patients with and without dementia. RESULTS: A total of 162/1217 (13.3%) patients were diagnosed with dementia. Among other associations, patients with dementia were significantly older with higher number of comorbidities, had lower estimated glomerular filtration rate (eGFR) and lower left ventricular ejection fraction (LVEF), (P < 0.05 for all analyses). Patients with dementia were significantly less likely to receive direct oral anticoagulants (DOACs; 27.2% vs 40.3%; P = 0.001) and were significantly more likely to be inadequately anticoagulated with warfarin (38.9% vs 28.6%; P = 0.008) than patients without dementia. After matching based on age, eGFR, LVEF, and CHA2DS2-VASC patients with dementia were significantly more likely to experience inferior overall survival (HR = 1.8; P = 0.001) and shorter time to thrombosis (HR = 2.3; P = 0.019). CONCLUSION: Our findings speak in support of increased thrombotic and mortality risks in patients with dementia, possibly due to inadequate anticoagulation and higher number of comorbidities.

Changes of recommended anticoagulation therapy in patients with atrial fibrillation and high thrombotic risk: long-term follow-up data from two hospital centers.

Aim : To investigate changes of anticoagulation therapy in patients with atrial fibrillation (AF) and high thrombotic risk.Methods : We retrospectively analyzed 1061 patients with non-valvular AF and indication for anticoagulation therapy referred in a period from 2013 to 2018 and followed-up for a median time of 38 months.Results : Therapy change occurred in 206 (19.5%) patients (195 switches and 11 permanent discontinuations). Only 37% of patients on warfarin had optimal dosing and their duration of therapy was significantly shorter compared to direct oral anticoagulants (DOACs; (adjusted HR 1.21, 95% CI 1.09-1.37). Therapy change occurred in only 33% of patients with poorly controlled warfarin, and in only 24% of patients that experienced a thrombotic event while taking warfarin. Optimal dosing was an independent factor for any therapy change during follow-up, irrespective of type of anticoagulant drug at baseline. DOAC swapping occurred in 39% of all DOAC to DOAC switches, with one bleeding event and no thrombotic events documented after a DOAC swap.Conclusion : High risk patients with AF rarely discontinue anticoagulation therapy. The need for therapy change should be emphasized in patients with non-optimal dosing, and in patients that experience thrombotic events while taking warfarin.

Cardiovascular mortality in liver and kidney transplant recipients: A retrospective analysis from a single institution.

ABSTRACT: Previous studies have demonstrated cardiovascular causes to be among the leading causes of death after liver (LT) and kidney transplantation (KT). Although both recipient populations have unique pre-transplant cardiovascular burdens, they share similarities in post-transplant exposure to cardiovascular risk factors. The aim of this study was to compare cardiovascular mortality after LT and KT.We analyzed causes of death in 370 consecutive LT and 207 KT recipients from in-hospital records at a single tertiary transplant center. Cardiovascular causes of death were defined as cardiac arrest, heart failure, pulmonary embolism, or myocardial infarction.After a median follow-up of 36.5 months, infection was the most common cause of death in both cohorts, followed by cardiovascular causes in KT recipients and graft-related causes in LT recipients in whom cardiovascular causes were the third most common. Cumulative incidence curves for cardiovascular mortality computed with death from other causes as the competing risk were not significantly different (P = .36). While 1-year cumulative cardiovascular mortality was similar (1.6% after LT and 1.5% after KT), the estimated 4-year probability was higher post-KT (3.8% vs. 1.6%). Significant pre-transplant risk factors for overall mortality after KT in multivariable analysis were age at transplantation, left ventricular ejection fraction <50%, and diastolic dysfunction grade 2 or greater, while significant risk factors for cardiovascular mortality were peripheral artery disease and left ventricular ejection fraction <50%. In the LT group no variables remained significant in a multivariable model for either overall or cardiovascular mortality.The present study found no significant overall difference in cardiovascular mortality after LT and KT. While LT and KT recipients may have similar early cardiovascular mortality, long-term risk is potentially lower after LT. Differing characteristics of cardiovascular death between these two patient populations should be further investigated.

The Risk of Falling and Consequences of Falling in Patients with Atrial Fibrillation Receiving Different Types of Anticoagulant.

OBJECTIVE: Our objective was to investigate the predictors of falls requiring a visit to the emergency department in patients with nonvalvular atrial fibrillation (AF) receiving different types of anticoagulants and to investigate the clinical consequences of falling in the same population. METHODS: A total of 1217 patients with nonvalvular AF from two institutions were retrospectively evaluated. Each patient underwent a physical examination, and clinical histories and medication profiles were taken from each patient at baseline. RESULTS: The median age of our cohort was 71 years; 52.3% were males, and 86.1% of patients were receiving anticoagulation at study baseline. The 5-year freedom-from-falling rate was 81.6%. The use and type of anticoagulation was not significantly associated with the risk of falling (P = 0.222), whereas higher Morse Fall Scale (MFS), CHA2DS2-VASC (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65-74 years, sex category), and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly [> 65 years], drugs/alcohol concomitantly) scores were significantly associated with a higher hazard of the first fall in univariate analyses. In the multivariate Cox regression model, MFS, older age, osteoporosis, higher levels of high-density lipoprotein cholesterol, higher diastolic blood pressure, and use of amiodarone, diuretics, or short- and medium-acting benzodiazepines were mutually independent predictors of the first fall. Of 163 patients, 93 (57%) had a bone fracture during the fall. Type of anticoagulation significantly affected survival after the first fall (P < 0.001): patients inadequately anticoagulated with warfarin had worse survival rates, and patients receiving apixaban and dabigatran had the best survival rates after the first fall. CONCLUSION: Older patients who had comorbidities and were taking amiodarone, diuretics, or short- or medium-acting benzodiazepines had the highest risk of falls. The type and quality of anticoagulation did not seem to affect the risk of falling but did significantly affect survival after the first fall.

Left atrium size and red cell distribution width predict atrial fibrillation progression from paroxysmal or persistent to permanent.

Objective: Stratifying patients with paroxysmal or short-term persistent atrial fibrillation (AF) who are at greater risk of developing permanent AF is challenging. Aim of our prospective study was to evaluate association of laboratory parameters (biochemistry and complete blood count (CBC)) together with standard demographic, clinical and echocardiography parameters, with AF progression.Methods: We prospectively recruited 579 patients with AF and divided them into two groups at index hospitalization: paroxysmal or persistent (non-permanent AF), and long-term persistent or permanent AF patients (permanent AF). Clinical, echocardiographic, and relevant CBC parameters were collected. Non-permanent AF patients were selected for follow-up, with a median follow-up time of 21 months. Endpoint was progression to permanent AF.Results: Out of 409 patients with non-permanent AF, 109 (26.6%) progressed within follow-up. In a multivariate Cox regression model only increased left atrium (LA) diameter (HR 2.16, 95% CI 1.20-3.87, p = 0.010), and increased red cell distribution width (RDW; HR 1.19, 95% CI 1.03-1.39, p = 0.022) showed significant independent association with progression. There were 221/409 patients with both LA ≤45 mm and RDW level ≤14.5% who progressed at a rate of only 17.6%, and showed relative risk of AF progression of 0.47 (95% CI 0.34-0.67; p < 0,001).Conclusion: Together with LA size, RDW was independently associated with AF progression. Patients with both LA size ≤45 mm and RDW level ≤14.5% are most probably the best candidates for rhythm control strategies.

Periprocedural myocardial and renal injury in patients undergoing elective percutaneous coronary interventions - is there an association?

Periprocedural myocardial injury (PMI) and contrast-induced nephropathy (CIN) are frequent complications of percutaneous coronary intervention (PCI) associated with early and late major adverse cardiovascular events. Both conditions are associated with similar risk factors, which could imply their possible association. The aim of our study was to assess the correlation of PMI and early postprocedural creatinine shift (ECS) as a marker of renal injury.A total of 209 hospitalized patients with stable coronary artery disease (CAD) were enrolled, who underwent an elective PCI in a period of 12 months. All patients had their serum high-sensitivity troponin I (hsTnI) measured at baseline and 16 hours after the PCI. PMI was defined according to the elevation of postprocedural hsTnI using criteria provided by both the most recent consensus documents as well as evidence-based data. Renal injury was evaluated using the ECS concept. Serum creatinine (SCr) was also measured at baseline and at 16 hours. ECS was defined as SCr >5% at 16 hours compared to baseline.Although incidence of both PMI (77.5%) and ECS (44.5%) were high, no association of these 2 conditions could be found. Further analyses of our data showed that diabetes is associated with a higher incidence of ECS, while patients on beta-blocker therapy had a lower incidence of ECS.In our study, no association between PMI and ECS was found. Additional studies with a larger number of patients and longer patient observation are needed to assess the correlation between PMI and CIN as well as to validate the attractive, but controversial, concept of ECS as an early marker of CIN.

Red cell distribution width in acute pulmonary embolism patients: A simple aid for improvement of the 30-day mortality risk stratification based on the pulmonary embolism severity index.

BACKGROUND: Pulmonary embolism (PE) severity index (PESI) well predicts 30-day mortality in acute PE patients, yet improvements have been advocated. OBJECTIVES: To evaluate predictivity of the red cell distribution width (RDW) through a comparison with PESI and to explore their interaction as a potential improvement in this respect. METHODS: Retrospective analysis of consecutive adult PE patients. RESULTS: Of the 299 patients, 19 severely unstable died within 48 h. Among the stabilized patients, 30-day mortality was 12.1% (34/280). With PESI ≤125, mortality was 4.9% (9/185), but it was 0.7% (1/140) if RDW ≤15.0% and 17.8% (8/45) if RDW >15.0%; with PESI >125, mortality was 26.3% (25/95), but it was 15.9% (7/44) if RDW ≤15.0% and 35.3% (18/51) if RDW >15.0%. Adjusted relative risk with PESI >125 vs. ≤125 was 17.5 (95%CI 2.37-129) at RDW ≤15.0% and 1.60 (0.76-3.36) at RDW >15.0%. CONCLUSIONS: Thirty-day mortality predictions based on the PESI score may be improved by accounting for RDW.

INADEQUACY OF VITAMIN K ANTAGONIST USE IN PATIENTS WITH ATRIAL FIBRILLATION - OVERVIEW OF EVERYDAY CLINICAL PRACTICE AT THE MERKUR UNIVERSITY HOSPITAL IN ZAGREB, CROATIA.

Atrial fibrillation is the most common cardiac arrhythmia. It increases the risk of death and thromboembolic events. Vitamin K antagonists reduce these risks. Disadvantages of vitamin K antagonist therapy are narrow therapeutic range and interactions with drugs and food. In a single center prospective study, we enrolled 249 patients with atrial fibrillation over a 12-month period. The aim of our study was to evaluate vitamin K antagonist use regarding the indication and adequate dose. Data on 249 consecutive patients with atrial fibrillation were collected before general availability of novel oral anticoagulants. Out of 249 patients, 160 (64.2%) had indication for oral anticoagulant therapy. Only 81 (50.6%) patients had vitamin K antagonist in therapy, 12 (14.8%) of them in adequate dose. We also analyzed 129 patients aged over 75, of which 109 (84.4%) had absolute indication for oral anticoagulant therapy. Only 34 (31.2%) patients aged over 75 had been receiving vitamin K antagonist therapy and 6 (17.6%) had the International Normalized Ratio values within the proposed therapeutic interval. We found a significantly higher rate of anticoagulant therapy introduction in patients under 75 years (p=0.03), but there were no significant differences in the adequacy of anticoagulant therapy (p=0.89) between these two populations. Our results showed clear inadequacies of vitamin K antagonist treatment with a growing need for a wider use of novel oral anticoagulants.

Mortality and causes of death among Croatian male Olympic medalists.

AIM: To compare the overall and disease-specific mortality of Croatian male athletes who won one or more Olympic medals representing Yugoslavia from 1948 to 1988 or Croatia from 1992 to 2016, and the general Croatian male population standardized by age and time period. METHODS: All 233 Croatian male Olympic medalists were included in the study. Information on life duration and cause of death for the Olympic medalists who died before January 1, 2017, was acquired from their families and acquaintances. We asked the families and acquaintances to present medical documentation for the deceased. Data about the overall and disease-specific mortality of the Croatian male population standardized by age and time period were obtained from the Croatian Bureau of Statistics (CBS). Overall and disease-specific standard mortality ratios (SMR) with 95% confidence intervals (CI) were calculated to compare the mortality rates of athletes and general population. RESULTS: Among 233 Olympic medalists, 57 died before the study endpoint. The main causes of death were cardiovascular diseases (33.3%), neoplasms (26.3%), and external causes (17.6%). The overall mortality of the Olympic medalists was significantly lower than that of general population (SMR 0.73, 95% CI 0.56-0.94, P=0.013). Regarding specific causes of death, athletes' mortality from cardiovascular diseases was significantly reduced (SMR 0.61, 95% CI 0.38-0.93, P=0.021). CONCLUSIONS: Croatian male Olympic medalists benefit from lower overall and cardiovascular mortality rates in comparison to the general Croatian male population.

Anthropometric and Laboratory Variables Related to Weight Loss-Comparison of Heart Failure Patients with Tumor Patients and Control Population.

BACKGROUND: Body weight loss is an important feature of heart failure (HF) and tumors. It is related to both reduced survival and adverse reactions to therapy in both of these conditions. The mechanisms of body weight loss in patients with HF and tumors are considered to be similar. Yet, studies comparing those two populations are generally lacking. The aim of this study was to compare anthropometric and laboratory data, related to weight loss, between patients with chronic HF and patients with different tumors as well as control population. METHODS: Laboratory and anthropometric data on 143 consecutive patients with chronic HF and malignant diseases as well as data for 20 controls were collected. RESULTS: Patients with HF had lower levels of C-reactive protein (CRP) and albumin compared to controls. Anthropometric measurements revealed lower body mass index (BMI), muscle strength, mid-arm circumference, and waist circumference in patients with HF compared to controls. Measurements of biceps, triceps, subscapular, and suprailiac skinfolds were also lower in HF group. Compared to solid tumor group, HF patients had lower levels of CRP and higher levels of hemoglobin. Solid tumor patients had lower values of BMI and subscapular skinfold thickness, as well as higher muscle strength compared to HF group. Finally, compared to patients with solid hematological tumors, HF group had lower levels of albumin, lower muscle strength, as well as lower mid-arm circumference. CONCLUSION: We found differences in anthropometric and laboratory features, related to weight loss, in patients with HF compared to control population that were expected. On the other hand, observed differences in HF group compared to patients with various tumors could imply different pathophysiological mechanisms of weight loss between those groups. Such data could serve as a cornerstone for studies with larger numbers of patients and deeper pathophysiological insight.

Association of chronic kidney disease with periprocedural myocardial injury after elective stent implantation: A single center prospective cohort study.

Coronary artery disease (CAD) is the leading cause of mortality in patients with chronic kidney disease (CKD). Patients with CKD who undergo percutaneous coronary intervention (PCI) may have more ischemic events than patients without CKD. The aim of our study was to determine the incidence of periprocedural myocardial injury (PMI) after elective stent implantation in patients with CKD using the Third Joint ESC/ACCF/AHA/WHF PMI definition.In a single center prospective cohort study, we enrolled 344 consecutive patients who underwent elective PCI in a period of 39 months. Serum troponin I (cTnI) concentrations were measured at baseline and at 8 and 16 hours after PCI. Periprocedural increase of cTnI, according to the most recent PMI definition, was used to define both the presence and intensity of PMI. Patients were further stratified according to the estimated glomerular filtration rate (eGFR) using 4 variable Modification of Diet in Renal Disease (MDRD) equation: control group with eGFR >90 mL/min/1.73 m and the CKD group with eGFR < 90 mL/min/1.73 m, with further subdivision according to the CKD stage.We found no significant difference in the incidence as well as intensity of the PMI in the control (>90 mL/min/1.73 m) and the CKD group (<90 mL/min/1.73 m) both 8 and 16 hours after PCI. When the CKD patients were further subdivided according to their CKD stage, there was again no difference in the intensity or incidence of PMI compared to the control group. Further analyses of our data showed angina pectoris CCS IV, bare metal stent (BMS) implantation, and treatment with angiotensin-converting enzyme inhibitors (ACEI) as independent predictors of PMI. Furthermore, the presence of hypertension was inversely related to the occurrence of PMI.Applying the new guidelines for PMI and using the eGFR equation most suitable for our patients, we found no association between PMI and CKD. Further analyses showed other factors that could potentially influence the occurrence of PMI.

Differences in routine laboratory parameters related to cachexia between patients with hematological diseases and patients with solid tumors or heart failure - is there only one cachexia?

BACKGROUND: Cachexia is a state of involuntary weight loss common to many chronic diseases. Experimental data, showing that cachexia is related to the enhancement of acute phase response reaction, led to the new definition of cachexia that included, aside from the principal criterion of weight loss, other "minor criteria", Amongst them are levels of C-reactive protein (CRP), albumin and hemoglobin. However, there is paucity of data regarding possible differences of these laboratory parameters in patients with various diseases known to be related to cachexia. METHODS: CRP, albumin and hemoglobin were evaluated in 119 patients, divided into two disease groups, hematological (ones with diagnosis of non-Hodgkin lymphoma or Hodgkin disease) and non-hematological (solid tumor patients and patients with chronic heart failure). Patients were further subdivided into two nutritional groups, cachectic and non-cachectic ones according to the principal criterion for cacxehia i.e. loss of body weight. RESULTS: We found that cachectic patients had higher levels of CRP, and lower levels of both hemoglobin and albumin compared to non-cachectic patients, regardless of the disease group they fitted. On the other hand, the group of hematological patients had lower levels of CRP primarily due to the differences found in the non-cachectic group. Higher levels of albumin were also found in the hematological group regardless of the nutritional group they fitted. Limitations of cut-off values, proposed by definition, were found, mostly regarding their relatively low sensitivity and low negative predictive value. CONCLUSIONS: As expected, differences in values of routine laboratory parameters used in definition of cachexia were found between cachectic and non-cachectic patients. Their values differed between hematological and non-hematological patients both in cachectic and non-cachectic group. Cut-off levels currently used in definition of cachexia have limitations and should be further evaluated.

[Antiaggregation therapy after percutaneous coronary intervention in a patient with thrombocytopenia: case report]. / Antiagregacijska terapija nakon perkutane koronarne intervencije kod bolesnika s trombocitopenijom--prikaz bolesnika.

Dual antiaggregation (antiplatelet) therapy is mandatory in patients having received a stent during percutaneous coronary intervention. This therapy usually consists of acetylsalicylic acid (100 mg per day) and clopidogrel (75 mg per day) for at least 6 to 12 months (depending on the type of stent). Such therapy has been shown to reduce significantly unwanted clinical events, although slightly increasing the risk of bleeding. Coronary stents must rarely be implanted in patients who have or develop thrombocytopenia. In such patients, the risk of bleeding is increased manifold. On the other hand, the risk of potentially fatal thrombotic events is unknown. In this case report, we present a patient who developed thrombocytopenia shortly (one month) after the stent had been implanted. After thorough clinical workup, we could not find the remediable cause of thrombocytopenia. Because of the potential of acetylsalicylic acid to induce thrombocytopenia, it was excluded from therapy and a double dose of clopidogrel (150 mg per day) was introduced. Then we decided to evaluate platelet function with the ADP aggregation test (which indicates the degree to which the function of platelets is blocked by clopidogrel) and aspirin resistance test (which indicates the degree to which the function of platelets is blocked by acetylsalicylic acid). In the first set of tests, the patient was shown to be hyperreactive to both substances. We then lowered the dose of clopidogrel to the standard dose and evaluated the function of platelets with the same tests two weeks later and the results were the same. Because the patient was without obvious and laboratory signs of bleeding, we decided not to change the prescribed antiplatelet therapy because of fear from potentially fatal thrombotic events. The use of dual antiplatelet therapy in patients with thrombocytopenia is particularly challenging. We believe that in such patients, firstly, the cause of thrombocytopenia should be sought for by thorough clinical investigation. If not found, as in our patient, tailoring of such therapy should be done using currently available aggregation tests. In such a way, patients could be protected from both excessive bleeding and potentially devastating thrombotic events. Unfortunately, this is a sole example and definite conclusions could only be made on larger studies.

[Pleural mesothelioma--case report]. / Mezoteliom pleure--prikaz bolesnika.

Pleural mesothelioma is a rare neoplasm with the incidence of 1-2 per million people. The incidence is higher in male population (10-30/million), whereas the incidence in female population is 2 per million. It occurs predominantly at older age (65+ years). The most common clinical manifestation of pleural mesothelioma is pleural effusion with dyspnea, which makes it a diagnostic problem since many cardiac diseases can have the same presentation. We report a case of pleural mesothelioma in an 80-year-old woman that presented with dyspnea and pleural effusion, which was at first considered as a sign of heart failure. Clinical presentation also included metabolic disorders and deep vein thrombosis, and the patient's epidemiologic history was negative, so diagnostic procedures including pleurocentesis were directed towards detection of the possible malignant disease. Cytologic analysis followed by biopsy pointed to the diagnosis of pleural mesothelioma. Persistent pleural effusions that do not coincide with cardiac disease, especially if accompanied by metabolic disorders and paraneoplastic syndromes, require additional diagnostic workup to identify the etiology of pleural effusion.

An unusual presentation of Gaucher's disease: aortic valve fibrosis in a patient homozygous for a rare G377S mutation.

Gaucher's disease (GD) has variable presentations, but cardiac involvement is a generally uncommon clinical manifestation of the disease. In the past 25 years, the underlying genetic disorder in GD has been well characterized, with almost 300 mutations identified in the glucocerebrosidase gene (GBA). Nevertheless, clear genotype-phenotype correlations have been confirmed only for the most frequent mutations. We present a female patient, who was known to have aortic valve pathology from the age of 30. Despite medical follow up, at the age of 60 she presented with heart failure (NYHA III). At that time echocardiography showed severe fibrosed aortic valve stenosis. Valvuloplasty was planned, when thrombocytopenia, previously considered to be autoimmune, became severe. Anemia and leukopenia were also noted. Moderate splenomegaly and severe bone marrow infiltration were found on MRI. Bone marrow aspiration revealed typical Gaucher cells and the enzyme activity assay confirmed the diagnosis. DNA investigation showed that the patient is homozygous for the G377S mutation. To our knowledge, of all mutations identified so far, only homozygosity for the D409H mutation has been associated with cardiovascular valvular disease in patients with a rare type 3c GD. G377S, found in our patient, is a rare mutation, previously reported as a 'mild' mutation, because of the finding that homoallelic patients were essentialy asymptomatic or had mild disease. Our patient, also homozygous for G377S mutation, had a severe form of type 1 GD, with rare cardiac valve involvement, which is a previously unreported clinical presentation for this mutation. This case further proves that patients with the same genotypes can have different phenotypes, emphasizing the influence of other genetic and/or environmental factors.

Role of angiogenesis in chronic lymphocytic leukemia.

Angiogenesis is a physiologic process of new blood vessels formation mediated by various cytokines called angiogenic and angiostatic factors. Although its potential pathophysiologic role in solid tumors has been extensively studied for more than 3 decades, enhancement of angiogenesis in chronic lymphocytic leukemia (CLL) and other malignant hematological disorders has been recognized more recently. An increased level of angiogenesis has been documented by various experimental methods both in bone marrow and lymph nodes of patients with CLL. Although the role of angiogenesis in the pathophysiology of this disease remains to be fully elucidated, experimental data suggest that several angiogenic factors play a role in the disease progression. Biologic markers of angiogenesis were also shown to be of prognostic relevance in CLL. The current findings provide the rationale for investigating antiangiogenic agents in CLL. In the current review angiogenesis in CLL is discussed and its potential diagnostic and therapeutic applications.

[Role of angiogenesis in the growth and progression of tumors. Treatment with angiogenesis inhibitors: from promising results in experimental animal models to the reality of clinical use]. / Uloga angiogeneze u rastu i progresiji tumora. Terapija inhibitorima angiogeneze: od obecavajucih rezultata pokusnih zivotinjskih modela do realnosti klinicke primjene.

The development of new blood vessels (angiogenesis) is necessary to sustain the growth of primary tumor as well as a process of tumor metastasis. Cancer cells activate the quiescent vasculature to produce new blood vessels via an "angiogenic switch". Understanding of molecular mechanisms involved in that process is essential for the development of antiangiogenic drugs. Drugs that inhibit angiogenesis could offer a treatment that is complementary to traditional chemotherapy. Chemotherapy directly targets tumor cells, which are prone to develop acquired drug resistance due to genetic instability. Antiangiogenic therapy is directed against endothelial cells in tumor stroma, which are genetically stabile. First results from animal studies supported the theory that endothelial cells do not develop drug resistance and had excellent results in inducing tumor quiescence. However, recent clinical trials showed that antiangiogenic therapy has limitations but that it can improve conventional therapeutic modalities of disseminated disease.