An overview of Personalized Medicine landscape and policies in the European Union.

BACKGROUND: The spread of Personalized Medicine (PM) over the last decade defined a revolution in healthcare systems. PM is among the priorities of the European Commission's research agenda, which funded the IC2PerMed international project aiming to integrate China into the International Consortium of PM (ICPerMed). In the context of this project, we mapped the existing policies related to PM in the European Union (EU) and at the EU Member States (EU-MS) level. METHODS: PubMed, Google Scholar, Google, Microsoft and national and international institutions' official repositories were searched in order to identify documents on PM-related policies, programmes and action plans at the EU and EU-MS level, published up to December 2020. RESULTS: We identified 28 policies in the EU aimed at improving public health promoting and fostering PM implementation, through some actions including the standardization of good medical practice, use of big data and digital innovation, data sharing and cross-border interoperability, healthcare sustainability, disease prevention and patients'/citizens' engagement. We identified 23 policies at EU-MS level which, notwithstanding national differences, have a common focus, such as patient-tailored treatment and targeted prevention, education of healthcare workers, research and innovation, big data harmonization and healthcare system sustainability. CONCLUSIONS: The definition of an integrated regulatory framework is essential to turn PM into an opportunity for citizens and patients with the involvement of all the stakeholders. This work can provide a valuable tool for decision-makers to define common approaches, priorities for research, development and increase international collaboration, which could overcome the fragmented European scenario and align the future direction on PM.

Systematic review of studies investigating the association between dietary habits and cutaneous malignant melanoma.

OBJECTIVE: Several papers have dealt with diet as a risk factor for cutaneous malignant melanoma (CMM). This study aimed to synthesize available data on the topic. STUDY DESIGN: A systematic review of observational studies assessing the association between dietary habits and CMM was performed. METHODS: Electronic databases were used to identify eligible articles. Quality was assessed through the Newcastle-Ottawa scale. Case-control and cohort studies evaluating the intake of food/nutrients through the assessment of dietary habits and the occurrence of CMM were considered eligible. Data comparing the highest and lowest levels of consumption were collected from single studies and described qualitatively as data combination was not possible. Results were reported as percentages on the basis of relative risks and odds ratios. RESULTS: Eighteen studies reported in 21 articles were selected. Cohort studies showed better quality than case-control studies. Most articles did not detect any significant association between food/nutrient intake and CMM, except for limited evidence of a protective role associated with fish, vegetables and fruit. Risk reduction was shown to be 35-37%, 40-57% and 34-46%, respectively, in studies reporting significant results. Similarly, few articles showed protective roles of beta-carotene and vitamins A, C, D and E, with risk reduction of 64%, 37-43%, 41%, 15-39% and 50-66%, respectively. CONCLUSION: A trend towards reduced risk of CMM associated with higher intake of fish, vegetables and fruit, as well as beta-carotene and vitamins A, C, D and E, has been shown but further research is needed to provide decisive data.

Size of bladder cancers: correlation among different types of measurement.

OBJECTIVE: It was the aim of this study to evaluate the accuracy of the measurement of tumor size comparing the objective size with that measured by preoperative cystoscopy, by preoperative ultrasound (US) and with the diameter described by the operator before the transurethral resection. PATIENTS AND METHODS: This study included 100 patients with bladder papillary endoscopic features of single or multiple neoplasms who were candidates for transurethral resection. The sizes of the same neoplasms measured during preoperative cystoscopy, preoperative US and described by the operator before the transurethral resection were evaluated. A statistical analysis of the errors of measurement was performed if compared with an objective measurement done with an ureteral catheter. RESULTS: The statistical analysis of the data shows that there are no substantial differences between the objective and subjective measurement, and therefore, the measurements reported by individual operators are reliable. On the contrary, the diameters given by preoperative cystoscopy and US differ significantly from the objective measurement. CONCLUSIONS: This study shows that the most reliable measurement is the subjective measurement made directly by the urologist in the operating room.

Non steroid treatment for eczema: results from a controlled and randomized study.

AIM: This study assesses the efficacy of a new non steroid anti-inflammatory product in comparison to Hydrocortisone Butyrate 0.1% Cream in healing eczematous dermatitis. METHODS: A bilateral controlled randomized pilot study was conducted in Italian adults affected by eczema with at least two symmetric lesions at baseline, respectively assigned to a non steroid cream or Hydrocortisone. The severity of lesions was judged through the Global Clinical Score (GCS) and the recovery was defined as a GSC equal to 0. The study investigated: 1) the differences in GCS between four points in time during therapy (baseline, four, eight, twelve weeks), according to medication received; 2) treatment efficacy. RESULTS: The study showed that time, treatment and interaction between treatment and time were associated with GCS; moreover, lesions treated with Hydrocortisone went better on the whole but the post-hoc analysis showed a significant clinical improving at each point in time only for the non steroid cream. At the end of the study, in the intention to treat analysis, lesions recovered in 76.1% and 40.3% patients treated with Hydrocortisone and with the non steroid cream respectively; in the per protocol population, recovery was achieved in 91.7% and 58.3% of cases. CONCLUSION: According to the results, the non steroid cream has been demonstrated effective in reducing the severity of eczema and may be used with continuing success in the long term treatment of the disease.

23-valent pneumococcal polysaccharide vaccine (PPV23) for the prevention of invasive pneumococcal diseases (IPDs) in the elderly: is it really effective?

INTRODUCTION: Incidence of invasive pneumococcal diseases (IPDs) in Italy is constantly increasing and that is particularly true among the elderly. 23-valent polysaccharide pneumococcal vaccine (PPV23) is recommended to this age group and offered in all Italian regions. However, efficacy of PPV23 on preventing IPDs is debated. We therefore performed a review of the most recent available meta-analyses in order to assess the efficacy of PPVs. METHODS: The literature search was conducted using PubMed and Scopus search engines. We used the following keywords: "pneumococcal", "polysaccharide", "vaccine", "efficacy", "elderly", "meta analysis". Only meta-analyses published in the last 7 years were selected. We examined the results of the selected meta-analyses and assessed their quality according to the PRISMA recommendations. RESULTS: The search returned 16 results in PubMed and 12 in Scopus: among them we selected 3 meta-analyses. According to our quality assessment, all meta-analyses showed generally positive results and almost all items of the PRISMA checklist were respected. However, the research protocol and the registration number were absent in all the 3 revisions and the flow-chart was not shown in Moberley's and Melegaro's works. In the study by Huss et al. the relative risk of developing IPDs among vaccinated subjects was 0.90 (95%CI: 0.46-1.77, I2 4.9%), indicating a very slight benefit after vaccination. This contrasts with the results of the Cochrane Review by Moberley et al., in which the PPVs showed a protective efficacy in reducing the risk of IPDs of 74% (OR 0.26, 95% CI: 0.15-0.46) with no statistical heterogeneity (I2 0%). Melegaro et al. found a reduction not statistically significant of the incidence of IPD of 65% (OR 0.35; 95% CI 0.08-1.49) among healthy elderly, while the global estimate of vaccine efficacy among high risk elderly was minimal (OR 0.80; 95% CI 0.22-2.88). CONCLUSIONS: Most of the studies suggest that the PPVs confer low protection against IPDs. Anyhow, their methodological heterogeneity does not allow definitive conclusions. While waiting to see the results of new trials about the efficacy of PPVs, in particular of PPV23, and the extension of the use of conjugate vaccine among the population over 65, stakeholders should be aware of the results of the meta-analyses discussed in this paper during the implementation of the vaccination programs for the elderly in Public Health.

Knowledge about pandemic flu among Italian health care workers (HCWs): an Italian survey.

INTRODUCTION: In case of pandemics, healthcare workers (HCWs) are the main actors and, at the same time, one of the main targets of preventive measures. This is what occurred in 2009 during the A/HINI pandemic flu. The aim of our survey was to get information about HCWs' knowledge of the A/HINI pandemic flu prevention. MATERIALS AND METHODS: A survey of 32 questions, 11 of which about knowledge towards A/H1N1 pandemic flu, created on the basis of a similar one by the Harvard School of Public Health, was made available on the Italian Journal of Public Health website during the month of October 2009. The survey was advertised with links from various professional websites and by emailing to HCWs' addresses taken from the Italian Society of Hygiene and Public Health (SItI) databases. Descriptive and univariate analyses were conducted in order to assess whether differences exist on the level of knowledge of HCWs (specifically Nurses and Physicians) about preventive measures against the A/H1N1 pandemic flu. RESULTS: 1,960 HCWs answered to the questionnaire, 1,711 (87.3%) Nurses and 249 (12.7%) Physicians. Both Nurses and Physicians seemed to have a high or moderately high interest for A/H1N1 pandemic flu (86.1% vs. 91.2% respectively, p = 0.03). Nurses indicated national newscasts (38.6%) and communications within hospitals or other workplaces (33.8%) as the source of most information about A/H1N1 pandemic flu. On the other hand Physicians got information mostly from Internet (41.8%), but also from communications within their hospital or other workplace (34.5%) (p < 0.001). Not all the Nurses and Physicians knew that contagion is possible by close contact (less than 1 metre) wit someone affected (74.0% and 88.0% respectively, p < 0.001), while 82.3% of Nurses and 71.1% of Physicians reported that face masks protected from getting infected (p < 0.001). CONCLUSION: Information and awareness campaigns on the influenza pandemic should be conducted firstly among HCWs, because of their importance--especially in case of pandemics--as a valuable resource at risk, as a contagion vehicle and as a source of information for the general population.

Influence of sociodemographic inequalities and chronic conditions on influenza vaccination coverage in Italy: results from a survey in the general population.

OBJECTIVE: To assess inequalities in vaccination against seasonal influenza determined by sociodemographic and health-related factors. STUDY DESIGN: A cross-sectional study was conducted using data from 128,040 subjects aged 1-89 years who participated the national survey 'Health Conditions and Health Care Services Use', conducted by the Italian National Centre of Statistics in 2005. METHODS: This analysis included people aged ≥65 years, and individuals of any age with chronic medical conditions. The outcome variable was vaccination or non-vaccination against influenza in the last 12 months, and the explanatory variables were gender, age, smoking habit, educational level, macro-region of residence, chronic medical conditions, occupational status, marital status, self-assessed health status and self-assessed household income. Univariate and multivariate analyses were conducted using Chi-squared test and multiple logistic regression models. For the latter analysis, results are presented as odds ratios (OR) and 95% confidence intervals (CI) of being vaccination against influenza in the last 12 months. RESULTS: Approximately 20% of subjects had been vaccinated against influenza in the previous 12 months. Older age (≥65 years), current smoker, poor health status, poor self-assessed household income and the presence of at least one chronic condition were positively associated with influenza vaccination (P < 0.05). The lowest ORs for influenza vaccination were found in current smokers (adjusted OR vs non-smokers 0.699, 95% CI 0.697-0.701), young adults (adjusted OR 15-24 years vs ≥65 years 0.073, 95% CI 0.072-0.073; adjusted OR 25-34 years vs ≥65 years 0.097, 95% CI 0.096-0.097), subjects with a lower secondary education or professional school (adjusted OR vs primary education 0.910, 95% CI 0.908-0.913), subjects living in the Islands (adjusted OR vs North-eastern Italy 0.760, 95% CI 0.757-0.763), and unemployed subjects (adjusted OR vs employed 0.867; 95% CI 0.859-0.875). The ORs for vaccination were lower for some chronic conditions (e.g. allergies, cirrhosis) than others (e.g. cancer, stroke, bronchitis). Younger age groups, including children aged 0-14 years, had lower ORs for vaccination. CONCLUSIONS: Socio-economic factors, such as gender, age, educational level, occupational status and macro-region of residence, affect influenza vaccination coverage rates in the Italian general population. In addition, some chronic medical conditions are an obstacle for vaccination.

Behaviours regarding preventive measures against pandemic H1N1 influenza among Italian healthcare workers, October 2009.

A survey on attitudes and behaviours towards preventive measures against pandemic H1N1 influenza 2009 was carried out during the month of October 2009 in Italy through an online questionnaire adapted to the Italian situation from a similar survey of the Harvard School of Public Health in the United States (US). Results show that the intention to get vaccinated against pandemic H1N1 influenza 2009 is generally low and that there are differences in attitudes and behaviours towards preventive measures against pandemic H1N1 influenza 2009 between physicians and nurses, especially concerning vaccination. Differences relate also to sex, region of residence and marital status.

[Study on mortality by specific cause among workers at a lead and zinc foundry in Sardinia]. / Studio di mortalità per cause specifiche in lavoratori di una fonderia di piombo e zinco della Sardegna.

The mortality of 918 Sardinian lead-smelter workers followed between 1972 and 2001 is reported. The assessment of individual exposure to inorganic lead was based on several environmental and blood lead measurements available, for each department and task, between 1985 and 2001. The mortality for all cancers was within the expected numbers (SMR 1.01, n 108). Even if not statistically significant, the mortality for gastric cancer (SMR 1.22, n 4), for lung cancer (SMR 1.21, n 18) and for lymphomas and leukaemias (SMR 1.82, n 6) was higher than that expected from the regional rates during the follow-up. Only for the lung cancer mortality a statistically significant upward trend with increasing categories of lead exposure was observed (SMR 1.96, 95% CI 1.02-3.68 for the highest exposure group). Our study, even if of small size, suggests an association between occupational exposure to inorganic lead and lung cancer risk.

[Intellectual quotient and environmental exposure to low doses of lead]. / Quoziente intellettivo ed esposizione ambientale a basse dosi di piombo.

The effects of low-level lead exposure on children's intelligence quotient (IQ) were investigated in 64 Sardinian adolescents (13-16 years old). To estimate potential early adverse effects on the Central Nervous System (CNS) due to very low-level lead, the Intelligence Quotient (IQ) of adolescents with present blood lead concentrations (PbB) generally below 10 microg/dl was measured. We analyzed blood lead concentration and individual IQ of 32 Sardinian children living in Portoscuso, a town 2 Km far from a lead smelter, and of other 32 controls living in S. Antioco, a town about 15 Km far from the same smelter. The Wechsler Intelligence Scale for Children Revised (WISC-R) was administered. The relation between IQ and blood lead concentration was estimated by linear multivariate models adjusting for several potential confounders, such as the educational and socio-economic level of the parents. The blood lead concentration was in average significantly higher in the Portoscuso group compared to controls. The linear model applied to the total population studied (n 64) showed that the blood lead concentration was inversely and significantly associated with IQ, with an extrapolated decline of 1.29 points in total IQ for each microg/dl increase of lead blood concentration. According to the recent scientific literature on this topic, results of our pilot study suggest the need to further lower the blood lead concentration for children to a threshold significantly below 10 microg/dl, value till now considered "safe" for the children's CNS.

Transmural heterogeneity of myocardial contraction and ischemia. Diagnosis and clinical implications.

Myocardial contraction behaves heterogeneously, being greater in subendocardial than in subepicardial layers. Similarly, during acute myocardial ischemia or infarction, the subendocardium is the first myocardial layer to suffer. Conventional two-dimensional echocardiography cannot distinguish the transmural extension of myocardial ischemia or infarction, showing akinesia also when only the subendocardium is affected. Novel ultrasonographic techniques (like tissue characterization with integrated backscatter or Doppler tissue imaging) and nuclear magnetic resonance tagging can investigate myocardial contraction in different transmural layers and distinguish subendocardial from transmural ischemia or infarction. With the advent of thrombolysis and primary angioplasty in the acute phase of myocardial infarction a correct diagnosis of the extension of myocardial necrosis cannot ignore its transmural wavefront development. The salvage of the subepicardial layer does not give direct information on overall myocardial thickening but is one of the major determinants of overall left ventricular dysfunction and size. Although it is still necessary to investigate this phenomenon, new ultrasonographic techniques give us important information and more opportunities to appropriate diagnosis and future treatment of cardiac patients.

[Silica, silicosis, and lung cancer: analysis if the literature and mortality studies of minor workers in Sardinia]. / Silice, silicosi e cancro del polmone: analisi della letteratura e studi di mortalità in minatori della Sardegna.

Starting from a short review of the recent epidemiological studies available in the international literature concerning the association between silica, silicosis and lung cancer, the results of two mortality studies performed in Sardinia are reported. The first study concerns a 20-year follow-up of 1741 miners employed in 1973 in two metalliferous Sardinian mines. In the second study the cause specific mortality of 724 patients with silicosis, firstly diagnosed by standard chest x-ray between 1964 and 1970 in our Institute, has been analysed by a cohort study extended to December 31, 1997. The findings indicate that the slight increased lung cancer mortality observed in these cohorts, more than to the severity of radiological silicosis or to the entity of the cumulative exposure to crystalline silica dust in itself, was significantly associated to other risk factors as cigarette smoking, airflow obstruction and radon-daughters exposure in underground mines.

Mortality for pancreatic cancer among aluminium smelter workers in Sardinia, Italy.

To investigate the relationship between exposure to polycyclic aromatic hydrocarbons (PAHs) and mortality for specifc cancer sites, 1152 men, employed for at least 1 year at a prebake aluminium smelter, were followed-up from 1972 until 31 December 2001. Exposure to PAHs was estimated from a detailed reconstruction of the working history experienced in the plant by each cohort member and from several environmental and personal shift-sampling measurements available, by task and working department, since 1979. Furthermore, information on smoking habits, previous jobs before engagement in the smelter and main clinical findings observed during the follow-up were collected from the personal medical files. This study showed no increased mortality for lung cancer or bladder cancer associated to exposure to PAHs. Mortality for pancreatic cancer, based on 6 observed deaths, was significantly higher than expected in the whole cohort (SMR 2.4; 95%CI 1.1-5.2) and particularly among workers employed in the anodes factory of the plant (SMR 5.0, 95%CI 2.1-12.1), where a relatively consistent exposure to PAHs has been estimated. The nested case-control study planned for pancreatic cancer cases, confirmed that, also after controlling for cigarette smoking, PAH exposure experienced in the anodes factory was associated with a significant increased risk of pancreatic cancer. A pre-existent diabetes mellitus and a potential occupational exposure to pesticides experienced in previous agricultural jobs were found as concurrent significant covariates increasing the risk. In conclusion, the relatively high exposure to PAHs, experienced in the anodes factory and particularly in the green-mill department of this prebake aluminium reduction plant, cannot be ruled out as one of the main factors in the multifactorial aetiology of the pancreatic cancers observed in this study.

[Cognitive and performance capacity among adolescents living near a lead and zinc smelter]. / Capacità cognitive e di performance in adolescenti residenti in prossimità di una fonderia di piombo e zinco.

To estimate potential early adverse effects on the Central Nervous System (CNS) due to very low exposure to inorganic lead, the Intelligence Quotient (IQ) of adolescents with present blood lead concentrations (PhB) generally below 10 micrograms/dl was measured. We analyzed blood lead concentration and individual IQ of 32 Sardinian adolescents living in Portoscuso, a town 2 Km far from a lead smelter, and of other 32 controls living in S. Antioco, a town about 15 Km far from the same smelter. The Wechsler Intelligence Scale for Children Revised (WISC-R) was administered. The relation between IQ and blood lead concentration was estimated by linear multivariate models adjusting for several potential confounders, such as the educational and socio-economic level of the parents. The blood lead concentration was in average significantly higher in the Portoscuso group compared to controls. The linear model applied to the total population studied (n 64) showed that the blood lead concentration was inversely and significantly associated with IQ, with an extrapolated decline of 1.29 points in total IQ for each microgram/dl increase of blood concentration. According to the recent scientific literature on this topic, results of our pilot study suggest the need to further lower the definition of an elevated blood lead concentration for children to a threshold significantly below 10 micrograms/dl, value till now considered "safe" for the children's CNS.

[Mortality from lung cancer among workers of a Sardinian lead smelter [Follow-up: 1972-2001]]. / Mortalità per cancro polmonare in lavoratori di una fonderia di piombo della Sardegna [Follow-up: 1972-2001].

The mortality of 918 Sardinian lead-smelter workers followed between 1972 and 2001 is reported. The assessment of individual exposure to inorganic lead was based on several environmental and blood lead measurements available, for each department and task, between 1985 and 2001. The mortality for all cancers was within the expected numbers (SMR 1.01, n 108). Even if not statistically significant, the mortality for gastric cancer (SMR 1.22, n 4), for lung cancer (SMR 1.21, n 18) and for lymphomas and leukaemias (SMR 1.82, n 6) was higher than that expected from the regional rates during the follow-up. Only for the lung cancer mortality a statistically significant upward trend with increasing categories of lead exposure was observed (SMR 1.96, 95% CI 1.02-3.68 for the highest exposure group). Our study, even if of small size, suggests an association between occupational exposure to inorganic lead and lung cancer risk.

Pregnancy-induced analgesia: a combined psychophysical and neurophysiological study.

BACKGROUND: To investigate changes in heat pain threshold and modifications in heat pain processing during pregnancy and labour, seventy-six nulliparous pregnant women were enrolled in two studies. METHODS: In the first study (psychophysical), 60 pregnant women underwent a quantitative sensory testing (QST) investigating heat perception in two body areas (right forearm and T10 dermatome) according to these groups: 32-33 gestational weeks (GW), 39-40 GW, early stage of active labour and 24 h after the delivery. In the other study (neurophysiological), contact heat-evoked potentials (CHEPs) were recorded in other 16 women at the 32nd GW and in 11 of these also at the 40th GW. RESULTS: The psychophysical study showed that heat pain threshold was significantly increased at the forearm at 32-33 GW (median ± IQR: 39.6 ± 0.7 °C), at 39-40 GW (40.6 ± 1.1 °C) and at early stage of active labour (40.8 ± 1.5 °C) as compared to 20 non-pregnant controls (p < 0.001). Heat pain threshold tested at T10 level was significantly increased at 32-33 GW (41.0 ± 1.6 °C), at 39-40 GW (42.1 ± 1.8 °C), and at early stage of active labour (42.3 ± 1.3 °C) as compared to the non-pregnant women (p < 0.001). The N2-P2 CHEP amplitude (main negative N2 and positive P2 components of the vertex biphasic potential) recorded from the pregnant women was significantly lower at the 40th than at the 32nd GW, after stimulation of both the forearm (p < 0.001) and the abdomen (p < 0.001). CONCLUSIONS: In pregnant women, there is a progressive increase of heat pain threshold and a reduction of the CHEP amplitude, suggesting that a general inhibitory mechanism may be involved.

Non-invasive coronary flow reserve is correlated with microvascular integrity and myocardial viability after primary angioplasty in acute myocardial infarction.

OBJECTIVE: To test whether preserved coronary flow reserve (CFR) two days after reperfused acute myocardial infarction (AMI) is associated with less microvascular dysfunction (" no-reflow" phenomenon) and is predictive of myocardial viability. DESIGN: 24 patients with anterior AMI underwent CFR assessment in the left anterior descending coronary artery (LAD) with transthoracic echocardiography and myocardial contrast echocardiography (MCE) 48 h after primary angioplasty in the LAD (mean 4 (SD 2) and 3 (1) days, respectively). Low-dose dobutamine echocardiography was performed 6 (3) days after AMI and follow-up echocardiography at three months. RESULTS: No-reflow extent was greater in patients with impaired CFR (< 2.5) than in those with preserved CFR (> 2.5) (55 (35)% v 11 (25)%, p < 0.001). MCE reflow was more common in patients with preserved CFR (8/12) than in those with reduced CFR (1/12, p < 0.05). Wall motion score index in the LAD territory (A-WMSI) was similar at the first echocardiography (2.14 (0.39) v 2.32 (0.47), NS), although it was better in patients with preserved CFR at dobutamine (1.38 (0.45) v 1.97 (0.67), p < 0.05) and follow-up echocardiography (1.36 (0.40) v 1.97 (0.64), p < 0.05). An inverse correlation was found between CFR and A-WMSI at dobutamine and follow-up echocardiography (r = -0.49, p = 0.016 and r = -0.55, p = 0.005) and between MCE and A-WMSI at dobutamine and follow-up echocardiography (r = -0.75, p < 0.001 and r = -0.75, p < 0.001). By multivariate analysis MCE reflow remained the only predictor of recovery at both dobutamine and follow-up echocardiography (odds ratio 1.06, 95% CI 1 to 1.1, p = 0.009). CONCLUSION: CFR is inversely correlated with the extent of microvascular dysfunction at MCE two days after reperfused AMI. CFR and MCE reflow early after AMI are correlated with myocardial viability at follow up.

Clinical applications of contrast echocardiography.

BACKGROUND: Contrast media, used in conjunction with newly developed echocardiographic techniques, can currently be used in several clinical settings: (1) the study of myocardial perfusion, (2) delineation of the endocardial border in technically difficult echocardiographic examinations, and (3) enhancement of low-intensity blood flow, especially coronary blood flow, to study coronary flow reserve. METHODS: Published studies were reviewed to identify the advantages of associating contrast perfusion with classic or new echocardiographic and ultrasonographic imaging techniques in the study of myocardial perfusion and coronary artery flow. RESULTS: Several studies demonstrated the usefulness of contrast echocardiography, even in patients with a bad acoustic window, in evaluating opacification of the left ventricle or in enhancing echocardiographic color Doppler studies of coronary flow and coronary flow reserve. Preliminary results of transthoracic echocardiographic studies of myocardial perfusion are described. CONCLUSIONS: The clinical applications of contrast echocardiography are effective in exploiting examinations that provide poor diagnostic information (ventricular cavity opacification) or in obtaining new physiopathologic data (microvascular opacification/perfusion and coronary flow reserve). The evaluation of coronary flow reserve by contrast-enhanced transthoracic Doppler ultrasonography is an attractive new diagnostic modality that points the way toward important new clinical applications of contrast echocardiography. This technique is useful in evaluating the severity of coronary artery disease of the left anterior descending coronary artery and in all clinical conditions in which the effects of therapeutic interventions aimed at improving coronary flow reserve need to be monitored.