European Society of Cardiology quality indicators for the prevention and management of cancer therapy-related cardiovascular toxicity in cancer treatment.

AIMS: To develop quality indicators (QIs) for the evaluation of the prevention and management of cancer therapy-related cardiovascular toxicity. METHODS AND RESULTS: We followed the European Society of Cardiology (ESC) methodology for QI development which comprises (i) identifying the key domains of care for the prevention and management of cancer therapy-related cardiovascular toxicity in patients on cancer treatment, (ii) performing a systematic review of the literature to develop candidate QIs, and (iii) selecting of the final set of QIs using a modified Delphi process. Work was undertaken in parallel with the writing of the 2022 ESC Guidelines on Cardio-Oncology and in collaboration with the European Haematology Association, the European Society for Therapeutic Radiology and Oncology and the International Cardio-Oncology Society. In total, 5 main and 9 secondary QIs were selected across five domains of care: (i) Structural framework, (ii) Baseline cardiovascular risk assessment, (iii) Cancer therapy related cardiovascular toxicity, (iv) Predictors of outcomes, and (v) Monitoring of cardiovascular complications during cancer therapy. CONCLUSION: We present the ESC Cardio-Oncology QIs with their development process and provide an overview of the scientific rationale for their selection. These indicators are aimed at quantifying and improving the adherence to guideline-recommended clinical practice and improving patient outcomes.

A cost-utility analysis of increasing percutaneous coronary intervention use in elderly patients with acute coronary syndromes in six European countries.

AIMS: Percutaneous coronary intervention reduces mortality in acute coronary syndrome patients but the cost-utility of increasing its use in elderly acute coronary syndrome patients is unknown. METHODS: We assessed the efficiency of increased percutaneous coronary intervention use compared to current practice in patients aged ≥75 years admitted for acute coronary syndrome in France, Germany, Greece, Italy, Portugal and Spain with a semi-Markov state transition model. In-hospital mortality reduction estimates by percutaneous coronary intervention use and costs were derived from the EUROpean Treatment & Reduction of Acute Coronary Syndromes cost analysis EU project (n = 28,600). Risk of recurrence and out-of-hospital all-cause mortality were obtained from the Information System for the Development of Research in Primary Care (SIDIAP) database from North-Eastern Spain (n = 55,564). In-hospital mortality was modelled using stratified propensity score analysis. The 8-year acute coronary syndrome recurrence risk and out-of-hospital mortality were estimated with a multistate survival model. The scenarios analysed were to increase percutaneous coronary intervention use among patients with the highest, moderate and lowest probability of receiving percutaneous coronary intervention based on the propensity score analysis. RESULTS: France, Greece and Portugal showed similar total costs/1000 individuals (7.29-11.05 m €); while in Germany, Italy and Spain, costs were higher (13.53-22.57 m €). Incremental cost-utility ratios of providing percutaneous coronary intervention to all patients ranged from 2262.8 €/quality adjusted life year gained for German males to 6324.3 €/quality adjusted life year gained for Italian females. Increasing percutaneous coronary intervention use was cost-effective at a willingness-to-pay threshold of 10,000 €/quality adjusted life year gained for all scenarios in the six countries, in males and females. CONCLUSION: Compared to current clinical practice, broadening percutaneous coronary intervention use in elderly acute coronary syndrome patients would be cost-effective across different healthcare systems in Europe, regardless of the selected strategy.

Remote postconditioning is more potent than classic postconditioning in reducing the infarct size in anesthetized rabbits.

PURPOSE: Postconditioning confers protection to the heart after a potentially lethal episode of prolonged ischemia. There is evidence that it may also be protective when applied at a distal artery. In the present study, we sought to determine whether remote postconditioning within the heart (local) or outside the heart (distal) is effective in salvaging the ischemic heart in vivo and to compare its effect with that of the classic postconditioning. METHODS: Twenty seven open chest New Zealand white anesthetized male rabbits were divided into four groups and were exposed to 30 min regional myocardial ischemia (isc), after ligation of a prominent coronary artery, followed by 3 h reperfusion (rep) after releasing the snare. Control group (n = 7) was subjected to no additional interventions, postC group (n = 6) was subjected to four cycles of 1 min isc/1 min rep of the same coronary artery at the beginning of reperfusion, remote local postC group (n = 7) to four cycles of 1 min isc/1 min rep of another coronary artery 30 s before the end of index isc and remote distal postC group (n = 7) to four cycles of 1 min isc/1 min rep of another (carotid) artery again 30 s before the end of index isc. Infarct size (I) and area at risk (R) were delineated with the aid of TTC staining and green fluorescent microspheres respectively and their ratio was expressed in percent (%I/R). RESULTS: Remote local and remote distal postC reduced the % I/R ratio (17.7 +/- 1.7% and 18.4 +/- 1.6%, respectively vs 47.0 +/- 2.5% in the control group, P < 0.01). Classic PostC had an intermediate protective effect (33.1 +/- 1.7%, P < 0.05 vs all the other groups). CONCLUSION: Remote postconditioning consisted of 1 min isc/1 min rep protects the ischemic rabbit heart in vivo, independently of the site of the remote artery. This intervention seems to confer a stronger protection than the classic postconditioning.

Heart disease in thalassemia intermedia.

Thalassemia intermedia (TI) presents with a clinical phenotype ranging between the severe, transfusion-dependent TM and the asymptomatic carrier state. Cardiovascular complications represent the primary cause of mortality both in TM and in TI. Several factors have been reported to interfere in the pathophysiology of cardiovascular abnormalities in TI, including high output state, vascular abnormalities, endothelial dysfunction, elastic tissue disorders, hypercoagulability, valvular abnormalities and, to a less extent, iron overload. These mechanisms end up affecting both left and right heart, hence leading to ventricular remodeling and finally heart failure.

Assessment and treatment of cardiac iron overload in thalassemia.

Cardiac disease remains the major cause of death in thalassemia major and iron overload is involved in heart failure development. Cardiac iron load and heart injury are evaluated by different means, among which CMR measurements remain the best method for estimation. In cases of heart iron overload, chelation treatment should be appropriately tailored in terms of intensification.

Alternative pharmacological interventions that limit myocardial infarction.

Despite current optimal treatment, the morbidity and mortality of coronary heart disease remain significant worldwide and open the way for the development of novel cardioprotective therapies. In the last two decades, a remarkable scientific effort has focused on the limitation of infarct size. Important input from experimental studies has led the way in this direction. However, clinical and preclinical results using various cardioprotective strategies to attenuate reperfusion injury have generally not been applicable for every day clinical practice. Protection of the ischemic myocardium is known to occur as a result of ischemic preconditioning (PC), in which repetitive brief periods of ischemia protect the heart from a subsequent prolong ischemic insult. Although PC is a powerful form of protection, it is of limited clinical application for obvious ethical and practical reasons. Another endogenous form of cardioprotection, similar to PC but applicable at the time of reperfusion, termed postconditioning (PostC), has been recently described. Short series of repetitive cycles of brief reperfusion and re-occlusion of the coronary artery applied at the onset of reperfusion, reduce the infarct size and coronary artery endothelial dysfunction. At present, pharmacological PC and PostC are possible alternative methods that may substitute pharmaceutical treatments the short ischemic insults. Adenosine, nicorandil and other agents have been already used as pharmacological mimetics of ischemic PC in multicenter trials. We summarize the recent research efforts on novel therapeutic strategies and on the design of new compounds, based on the accumulated knowledge of the ligands, receptors and intracellular signaling pathways of PC and PostC.

The heart failure pandemic: The clinical and economic burden in Greece.

BACKGROUND: The objective of this study was to identify the epidemiological and clinical characteristics of heart failure (HF) patients in Greece as well as the economic burden and the distribution of costs for the management of the disease. METHODS: Eight Greek secondary and tertiary cardiology centres from different cities have participated in a prospective, observational survey, the ESC HF Pilot Survey. 307 patients with HF, 177 hospitalised and 130 outpatients, have been recruited and monitored for 12months. Clinical and epidemiological data, along with data on mortality, hospitalisations and health care resources used have been collected. The economic evaluation was conducted from the social security system perspective. RESULTS: The annual mortality rate was 24.3% for the hospitalised patients vs 7.7% for the outpatients (P<0.001) and the annual rehospitalisation rate was 42.9% vs 19.2% respectively (P<0.001). Kaplan-Meier analyses revealed that patients with kidney dysfunction, S3 gallop and higher NYHA class have a significantly worse survival. The mean annual economic burden of the social security system per HF patient was estimated at €4411±4764. About two thirds of this cost is due to in-patient care. CONCLUSIONS: Despite the progress in the management of the disease, about one in four hospitalised patients dies and four in ten are rehospitalised in less than one year. Moreover, the disease imposes a significant economic burden for the social security system and national economy. Their findings suggest that there is still need of more effective drug treatment and efficient disease management programs focused in the reduction of the hospital admissions.

A simple score for early risk stratification in acute heart failure.

INTRODUCTION: The use of many acute heart failure (AHF) risk scores is cumbersome. We therefore developed a simple AHF risk score (AHFRS) for early risk stratification. METHODS: The study consisted of a prospective derivation cohort (PDC; N=104; age, 77[21] years; LVEF (%), 35[29]) and a retrospective validation cohort (RVC; N=141; age, 76[15] years; LVEF (%), 35[25]). Clinical, echocardiography and laboratory assessment was performed at admission. The study end-point was death from any cause or HF-rehospitalization at 1year. RESULTS: In the PDC 46 (44.2%) patients experienced the end-point. Independent prognostic factors of outcome were hypertension (HTN) history, myocardial infarction (MI) history, and admission red cell distribution width (RDW). Multivariate logistic regression indicated 8-, 4-, and 3-times higher odds ratio for development of study end-point in patients without a HTN history, with MI history, and RDW≥15% (median) respectively. Thus in AHFRS, 2 points were assigned for absence of HTN history, 1 point for presence of MI history, and 1 point for RDW values ≥15% (0 best possible, whereas 4 worst possible score). The AHFRS identified patients who developed the end-point in the PDC with an area under the ROC curve (AUC) of 0.80 [95% C.I.: (0.71, 0.87)] denoting a high discriminative ability. These findings were confirmed in the RVC, in which the endpoint occurred in 52 (36.9%) patients and the AUC for the AHFRS was 0.82 [95% C.I.: (0.73, 0.89)]. CONCLUSIONS: AHFRS is easily obtained at admission and accurately risk stratifies AHF patients.

Hypocalcemic heart failure in thalassemic patients.

Hypocalcemic cardiomyopathy in primary or secondary hypoparathyroidism is usually refractory to conventional treatment of cardiac failure. We report the case of a thalassemic patient with severe cardiac failure that might have been attributed to several factors, such as hemosiderosis, hypomagnesemia, and hypocalcemia, refractory to conventional cardiac therapy. Cardiac echocardiography showed impaired biventricular performance, and laboratory analyses revealed hypoparathyroidism due to hemosiderosis. When concomitant treatment of heart failure and calcium supplementation was initiated, correction of hypocalcemia resulted in clinical and laboratory improvement, providing strong evidence in support of our hypothesis about hypocalcemic myocardiopathy.

Exercise-induced myocardial perfusion abnormalities in sickle beta-thalassemia: Tc-99m tetrofosmin gated SPECT imaging study.

PURPOSE: To determine the mechanism of myocardial ischemia in patients with sickle beta-thalassemia, we performed a scintigraphic evaluation of myocardial perfusion during exercise. SUBJECTS AND METHODS: We studied 30 patients with sickle beta-thalassemia, (mean [+/-SD] age, 37 +/- 10 years) who had no electrocardiographic (ECG), radiographic, or echo-Doppler signs of pulmonary hypertension, left ventricular hypertrophy, or impaired contractility. All patients had a hemoglobin level greater than 7 g/dL. Treadmill exercise test was performed according to the Bruce protocol. Myocardial perfusion was assessed by single-photon emission computed tomography, using Tetrofosmin Tc-99 m Myoview as radiotracer, at peak exercise and again 4 hours later. RESULTS: Eight patients (27%) developed stress-induced scintigraphic perfusion abnormalities that were reversible in all but 1 patient. Subsequent coronary angiograms were normal in all 8 patients. ST segment depression was seen during exercise in 5 of the 7 patients who had reversible perfusion defects. Except for a significantly greater white blood cell count, these 5 patients did not differ from the rest of patients by sex, age, hemoglobin level, percentage hemoglobin F, beta-thalassemia genotype, or risk factors for coronary artery disease. Three of the 5 patients with perfusion and ECG abnormalities (and another with only perfusion defects) developed a stress-induced sickling crisis. CONCLUSION: Physical stress may induce myocardial ischemia in sickle beta-thalassemia patients with normal coronary arteries and elicit painful crises. The sickling process, activated by exercise, could be the common underlying mechanism.

Doppler-determined peak systolic tricuspid pressure gradient in persons with normal pulmonary function and tricuspid regurgitation.

The Doppler-estimated peak systolic tricuspid pressure gradient is the most reliable noninvasive method for the evaluation of pulmonary artery systolic pressure in patients with tricuspid regurgitation. Our goal was to evaluate the range of this gradient in healthy persons and determine a normal upper limit. We studied 53 healthy persons (34 women, 19 men; aged 14 to 55 years, mean 38.9 +/- 12.7 years) who did not smoke and who had an adequate Doppler signal of tricuspid regurgitation. The presence of pulmonary or cardiac disorders was excluded by a review of the subject's medical history in addition to physical examination, spirometry, arterial blood gasses determination, electrocardiography, chest x-ray examination, and rest echocardiography. Tricuspid gradient ranged from 12.6 to 29. 3 mm Hg (mean 19.3 +/- 4.0); 35.8% of patients had values higher than 20 mm Hg. In conclusion, a tricuspid gradient of 30 mm Hg may be considered as the upper normal limit. The different approaches for estimating mean right atrial pressure are also discussed.

Haemodynamic factors and the important role of local low static pressure in coronary wall thickening.

UNLABELLED: BACKGROUND/STUDY OBJECTIVES: The purpose of our study was to investigate the possible correlation between blood flow physical parameters and the wall thickening in typical human coronary arteries. METHODS: Digitized images of seven transparent arterial segments prepared post-mortem were adopted from a previous study in order to extract the geometry for numerical analysis. Using the exterior outline, reconstructed forms of the vessel geometries were used for subsequent computational fluid dynamic analysis. Data was input to a pre-processing code for unstructured mesh generation. The flow was assumed to be two-dimensional, steady, laminar with parabolic inlet velocity profile. The vessel walls were assumed to be smooth, inelastic and impermeable. Non-Newtonian power law was applied to model blood rheology. The arterial wall thickening was measured and correlated to the wall shear stress, static pressure, molecular viscosity, and near wall blood flow velocity. RESULTS: Wall shear stress, static pressure and near wall velocity magnitude exhibit negative correlation to wall thickening, while molecular viscosity exhibits positive correlation to wall thickening. CONCLUSION: There is a strong correlation between the development of vessel wall thickening and the blood flow physical parameters. Amongst these parameters the role of local low wall static pressure is predominant.

A Java-based electronic healthcare record software for beta-thalassaemia.

BACKGROUND: Beta-thalassaemia is a hereditary disease, the prevalence of which is high in persons of Mediterranean, African, and Southeast Asian ancestry. In Greece it constitutes an important public health problem. Beta-thalassaemia necessitates continuous and complicated health care procedures such as daily chelation; biweekly transfusions; and periodic cardiology, endocrinology, and hepatology evaluations. Typically, different care items are offered in different, often-distant, health care units, which leads to increased patient mobility. This is especially true in rural areas. Medical records of patients suffering from beta-thalassaemia are inevitably complex and grow in size very fast. They are currently paper-based, scattered over all units involved in the care process. This hinders communication of information between health care professionals and makes processing of the medical records difficult, thus impeding medical research. OBJECTIVES: Our objective is to provide an electronic means for recording, communicating, and processing all data produced in the context of the care process of patients suffering from beta-thalassaemia. METHODS: We have developed - and we present in this paper - Java-based Electronic Healthcare Record (EHCR) software, called JAnaemia. JAnaemia is a general-purpose EHCR application, which can be customized for use in all medical specialties. Customization for beta-thalassaemia has been performed in collaboration with 4 Greek hospitals. To be capable of coping with patient record diversity, JAnaemia has been based on the EHCR architecture proposed in the ENV 13606:1999 standard, published by the CEN/TC251 committee. Compliance with the CEN architecture also ensures that several additional requirements are fulfilled in relation to clinical comprehensiveness; to record sharing and communication; and to ethical, medico-legal, and computational issues. Special care has been taken to provide a user-friendly, form-based interface for data entry and processing. RESULTS: The experience gained through the use of JAnaemia in 4 Greek hospitals reveals a significant contribution towards (1) improvement of the quality of the data being recorded, since data entry is guided by appropriate forms, (2) easier cooperation between physicians, who share a common information repository, and (3) increased processing capabilities, which facilitate medical research. CONCLUSIONS: JAnaemia appears to be a useful tool, which can improve the quality of care offered to beta-thalassaemic patients in Greece.

Impact of ß-thalassemia trait carrier state on cardiovascular risk factors and metabolic profile in patients with newly diagnosed hypertension.

Thalassemia minor (Tm), the ß-thalassemia carrier state, is followed by favorable lipidemic profile and seems to protect against myocardial infarction mainly in men. However, the cardiovascular risk factor (CRF) and metabolic profile of these subjects has not been thoroughly addressed, although it is not known whether gender differences are involved. We evaluated CRFs, metabolic parameters and risk-prediction equations along with renal function and selected echocardiographic indices in 23,680 consecutive subjects, that is, 11,192 women and 12,488 men, with newly diagnosed hypertension according to the presence or absence of Tm. Of 23,680 patients, 548 (2.3%) had Tm. Compared with patients without Tm, Tm cases had similar gender distribution, age, body mass index and blood pressure. Besides having a better lipidemic profile, Tm patients were less frequently smokers (25% vs. 32%, P<0.001), had a lower prevalence of metabolic syndrome (26% vs. 39%, P<0.001) and lower HeartSCORE and INTERHEART scores (P<0.001). Tm patients also had lower levels of fibrinogen and plasminogen activator inhibitor-1 (P<0.001), lower serum creatinine and higher estimated glomerular filtration rate (P<0.001), lower prevalence of left ventricular hypertrophy (35% vs. 48%, P<0.001) and higher total and mid-wall fractional shortening (P=0.03 and <0.001, respectively). Most of these differences were consistent in both genders, whereas the HeartSCORE and the echo indices were significantly better in Tm only in women. Among patients with newly diagnosed hypertension, those with Tm have a better overall CRF and metabolic profile, beyond the well-known differences in serum lipids. Compared with men, women seem to be at least equally protected.

Evaluation of left atrial longitudinal function in patients with hypertrophic cardiomyopathy: a tissue Doppler imaging and two-dimensional strain study.

OBJECTIVE: We sought to quantify left atrial longitudinal function by tissue Doppler (TDI) and two-dimensional (2D) strain in patients with hypertrophic cardiomyopathy (HCM). DESIGN: Case-control study. SETTING: Tertiary university hospital. PATIENTS: 43 consecutive patients with familial HCM, aged 49 (SD 18) years, along with 21 patients with non-HCM left ventricular hypertrophy (LVH, aged 52 (12) years) and 27 healthy volunteers (aged 42 (13) years). INTERVENTIONS: Subjects were studied by both TDI and 2D left atrial strain during all three atrial phases (reservoir, conduit, contractile), as well as by left ventricular systolic strain; total atrial deformation (TAD) was defined as the sum of maximum positive and maximum negative strain during a cardiac cycle. MAIN OUTCOME MEASURES: Left atrial longitudinal function. RESULTS: Both TDI and 2D atrial strain and TAD were significantly reduced in HCM, compared to the other two groups in all atrial phases (p<0.001 in most cases); left ventricular systolic strain was also significantly reduced in HCM (p<0.001). Adding 2D contractile atrial strain to a model of conventional echo measurements (including left atrial diameter and volume index, interventricular septal thickness and E/A ratio and E/e' ratios) increased its prognostic value in differentiating HCM from non-HCM LVH (p value of the change <0.001), while addition of TDI atrial strain or left ventricular strain did not. A cut-off for 2D contractile strain of -10.82% discriminated HCM from non-HCM LVH with a sensitivity of 82% and a specificity of 81%. Intra-observer and inter-observer variabilities for atrial strain in HCM were 16% and 17.5% for TDI and 8% and 9.5% for 2D, respectively. Processing time per case in HCM was 12.5 (2.6) minutes for TDI versus 3.8 (1.2) minutes for 2D strain (p<0.001). CONCLUSION: Left atrial longitudinal function is reduced in HCM compared to non-HCM LVH and healthy controls. In addition, 2D atrial strain has an additive value in differentiating HCM from non-HCM LVH and it is more reproducible and less time consuming than TDI strain.

Clinical and prognostic implications of self-rating depression scales and plasma B-type natriuretic peptide in hospitalised patients with chronic heart failure.

BACKGROUND: Depression is common among patients with chronic heart failure (CHF) and has been independently associated with a poorer prognosis. PURPOSE: This study evaluated the clinical and prognostic value of depression scales (Beck Depression Inventory (BDI), Zung Self-rating Depression Scale (Zung SDS)) along with plasma B-type natriuretic peptide (BNP) in CHF. METHODS: 155 hospitalised CHF patients (ejection fraction 26.9% (SD 6.4%)) were studied by depression (BDI, Zung SDS) and functional questionnaires (Kansas City Cardiomyopathy Questionnaire (KCCQ), Duke Activity Status Index (DASI)), BNP and 6-minute walk test (6MWT). Patients were followed for 6 months for cardiovascular events, including death from any cause or rehospitalisation for CHF decompensation. RESULTS: Seventy-six (49%) patients with depressive symptoms, as estimated by both scales, had significantly lower DASI and KCCQ scores (13.2 (SD 9.9) vs 23.6 (SD 13.0) and 26.6 (SD 15.0) vs 45.0 (SD 17.0), respectively; p<0.001), higher BNP (921 (SD 889) vs 439 (SD 267) pg/ml, p = 0.001) and reduced 6MWT (270 (SD 130) vs 337 (SD 133); p<0.001). According to logistic regression analysis, Zung SDS and BNP were independently associated with adverse clinical outcomes; values of Zung SDS >or=40 and of BNP >or=290 pg/ml predicted future events with a sensitivity of 82% and 94% and a specificity of 45% and 46%, respectively. The combination of Zung SDS plus BNP had an additive prognostic value, predicting events with a sensitivity of 77% and a specificity of 70% (event-free survival: Zung <40 and BNP <290 pg/ml; 170 (SD 9) days; Zung >or=40 and BNP <290 pg/ml, 159 (SD 14) days; Zung <40 and BNP >or=290 pg/ml, 118 (SD 15) days; Zung >or=40 and BNP >or=290 pg/ml, 73 (SD 8) days, p<0.001). CONCLUSIONS: CHF patients with depressive symptoms have impaired physical activity, associated with excessive neurohormonal activation. Among the studied scales, Zung SDS seemed to independently predict clinical outcome, especially in patients with increased plasma BNP concentration. Hence, the combination of those two modalities provides a practical means for risk stratification in CHF.

Effects of serial levosimendan infusions on left ventricular performance and plasma biomarkers of myocardial injury and neurohormonal and immune activation in patients with advanced heart failure.

BACKGROUND: Levosimendan is a novel inodilator that improves central haemodynamics and symptoms of patients with decompensated chronic heart failure. The role, however, of repeated levosimendan infusions in the management of these patients has not yet been properly assessed. PURPOSE: This randomised placebo-controlled trial investigated the effects of serial levosimendan infusions on cardiac geometry and function, and on biomarkers of myocardial injury and neurohormonal and immune activation (troponin T, N-terminal B-type natriuretic pro-peptide (NT-proBNP), C reactive protein (CRP) and interleukin (IL) 6) in patients with advanced heart failure. METHODS: 25 patients with decompensated chronic heart failure were randomised (2:1) to receive five serial 24-h infusions (every 3 weeks) of either levosimendan (n = 17) or placebo (n = 8), and were evaluated echocardiographically and biochemically before and after each drug infusion and 30 days after the final infusion. RESULTS: Following treatment, cardiac end-systolic and end-diastolic dimension and volume indices were significantly reduced only in the levosimendan-treated patients (p<0.01). A significant decrease in NT-proBNP (p<0.01), high-sensitivity CRP (p<0.01) and plasma IL6 (p = 0.05) was also observed in the levosimendan group, whereas these markers remained unchanged in the placebo group; similar changes were observed after each drug infusion. Although the number of patients with a positive troponin T (>or=0.01 ng/ml) was not different between the two groups at baseline, it was significantly higher in the placebo-treated group during the final evaluation (p<0.05). CONCLUSION: Serial levosimendan treatments improved left ventricular performance and modulated neurohormonal and immune activation beneficially in patients with advanced heart failure, without increasing myocardial injury.

Transfusional hemosiderosis and combined chelation therapy in sickle thalassemia.

Although the indications for transfusions in sickle cell syndromes are well listed, and chronic transfusion has become practicable since the recent advances in chelation therapy have essentially eliminated the risk of secondary iron overload, multi-transfused, non-compliant to long-term chelation therapy patients confront the complication of iron overload and secondary hemosiderosis. In thalassemia major patients, combined therapy with desferrioxamine and deferiprone has maximized tissue iron removal and may reduce the overall occurrence of hemosiderotic heart failure. Despite this, safety and contradictions of chelating agents are still controversial. The aim of this report is to present the results of this combination in a long-term transfused sickle beta-thalassemic patient suffering from severe heart failure and liver dysfunction.

Reversal of heart failure in thalassemia major by combined chelation therapy: a case report.

In patients with thalassemia major (TM) who are non-compliant with long-term desferrioxamine (DFO) chelation, survival is limited mainly because of cardiac complications of transfusional hemosiderosis. Combined chelation therapy with DFO and deferiprone has maximized the efficacy of the therapy and reduced cardiological complications. The aim of this report is to present the results of this combination in a desperate case of heart failure.

Comparison of docetaxel and docetaxel-irinotecan combination as second-line chemotherapy in advanced non-small-cell lung cancer: a randomized phase II trial.

BACKGROUND: The aim of this study was to evaluate whether docetaxel (taxotere) treatment with or without irinotecan improved patient outcomes with similar toxicity in recurrent non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with recurrent platinum-refractory NSCLC with Eastern Cooperative Oncology Group performance status of 0-2 were randomized to either docetaxel 30 mg/m(2) and irinotecan 60 mg/m(2) (days 1 and 8) or docetaxel 75 mg/m(2) (day 1), both administered every 3 weeks. RESULTS: A total of 130 patients were randomized. The response rate (RR) (20% versus 14%), overall survival (6.5 months versus 6.4 months) and 1-year survival (37% versus 34%) were similar in the combination and docetaxel arms, respectively. The combination arm demonstrated a longer time to tumor progression (TTP) (5.6 versus 4.8 months; P=0.065). Grade 3-4 neutropenia and anemia were similar in the combination and docetaxel arms. Grades 3-4 non-hematological toxicity (except diarrhea) was mild and was similar in the two groups. Grade 3-4 thrombocytopenia (17% versus 6%; P=0.04) and diarrhea (12% versus 3%; P=0.05) occurred more frequently in the combination arm. CONCLUSIONS: The administration of irinotecan with docetaxel in platinum-refractory NSCLC prolonged TTP, but did not improve significantly RR, median survival or 1-year survival. Second-line docetaxel monotherapy offers significant and reproducible efficacy in platinum-refractory NSCLC.