Tomislav Letilović

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. Cancer 2006.

Influence of additional criteria from a definition of cachexia on its prevalence—good or bad thing?

Background/Objectives:Cachexia is a state of involuntary weight loss. The latest generic definition states that aside from weight loss, patient needs to fulfill additional criteria to be diagnosed with cachexia. New, condition-specific definitions also take the weight loss as a principal criterion, and additional criteria are not mandatory but are a part of further assessment. The aim of this study was to reveal the influence of additional criteria on the prevalence of cachexia in patients with various diseases linked to cachexia. Owing to this, we used the last generic definition. Possible differences in clinical presentations of patients with documented weight loss, with the respect of fulfillment of additional criteria were sought.Subjects/Methods:Clinical and anthropometric data on 137 consecutive patients with malignant diseases and chronic heart failure from a single institution were collected.Results:Fourty-two (30.6%) patients had >5% weight loss in the last 12 months. Only 30 (21.8%) of them were found to meet additional three out of five criteria proposed by the new definition. This observed difference in the prevalence of cachexia diagnosed with or without using additional criteria was found to be significant (P=0.0006). Comparison of clinical/laboratory data showed significantly higher levels of C-reactive protein and lower levels of albumin, as well as lower measurements of mid-arm circumference, triceps and suprailiac skinfolds in patients that fulfilled additional criteria. Survival analysis did not show reduced survival of patients fulfilling additional criteria.Conclusions:Additional criteria ‘reduce’ the prevalence of cachexia. They are indicative of differences in laboratory and clinical features of cachectic patients but do not influence their survival.

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?

BackgroundCachexia 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.MethodsCRP, 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.ResultsWe 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.ConclusionsAs 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.

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

AbstractCoronary 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 m2 and the CKD group with eGFR < 90 mL/min/1.73 m2, 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 m2) and the CKD group (<90 mL/min/1.73 m2) 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.

Angiographic characteristics and clinical relations of coronary collaterals in chronic total occlusion lesions

2018;13(1-2):48. LITERATURE 1. Meier P, Schirmer SH, Lansky AJ, Timmis A, Pitt B, Seiler C. The collateral circulation of the heart. BMC Med. 2013 Jun 4;11:143. https://doi.org/10.1186/1741-7015-11-143 Introduction: Coronary collaterals (CC) are anastomotic connections that can provide an alternative blood supply. They are especially important in the case of the vessel occlusion as they are prerequisite of viability. Collaterals have an indispensable role in any type of chronic total occlusion (CTO) intervention.1 Aim of our study was to analyze angiographic characteristics and clinical relations of collaterals in CTO patients.

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.

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.