[Short-term effects of PM10 on cause-specific mortality and the role of long-term environmental pressures in the industrial areas of Brindisi and Civitavecchia]. / Effetti a breve termine del PM10 sulla mortalità causa-specifica e ruolo delle pressioni ambientali di lungo periodo nelle aree industriali di Brindisi e Civitavecchia.

OBJECTIVES: the health status of people living near industrial plants is often exposed to several environmental risk factors, including air pollution. The aim of this study is to assess the relationship between daily PM10 levels and cause-specific mortality in a selection of municipalities near two industrial plants from 2006 to 2015. DESIGN: a time-series design with Poisson regression adjusted for a predefined set of confounders was used to quantify the association between exposure, calculated as daily PM10 levels extrapolated from machine-learning models using satellite data, and cause-specific mortality. SETTING AND PARTICIPANTS: twenty municipalities near the thermal power plants in Civitavecchia and Brindisi were selected. The municipalities were then divided into three scenarios of chronic exposure derived from SPRAY simulation models of pollutant deposition. MAIN OUTCOME MEASURES: daily cause-specific non-accidental, cardiovascular, and respiratory deaths defined according to the International Classification of Diseases code at the municipality level. RESULTS: a total of 41,942 deaths were observed in the entire area (10,503 in the Civitavecchia area and 31,439 in the Brindisi area), of which approximately 41% were due to cardiovascular causes and 8% due to respiratory causes. The association showed an increase in shortterm effects in municipalities with higher chronic levels of pollution exposure. For example, risk estimates reported as percentage increases per 10-unit increase in PM10 were 6.7% (95% CI 0.9, 12.7%) in scenario 3 (highest exposure) compared to 4.2% (-1.2, 9.9%) and 2.7% (-4.2, 10.2%) in scenarios 2 and 1, respectively, in the area near the Civitavecchia plant. Similar effects were observed for the Brindisi area. CONCLUSIONS: despite the well-documented relationship between short-term pollution and mortality, it appears that greater chronic exposure to industrial pollutants leads to increased short-term effects of PM10. The limited number of events suggests that this study could serve as a starting point for a larger investigation.

[Long-term exposure to air pollution and incidence of coronary heart diseases and stroke in the longitudinal metropolitan studies (LMS) network: the BIGEPI project]. / Esposizione di lungo periodo all'inquinamento atmosferico e incidenza di malattia coronarica acuta e ictus nella rete degli studi longitudinali metropolitani: il progetto BIGEPI.

OBJECTIVES: to assess the potential of using longitudinal metropolitan studies (LMS) to study the association between long-term exposure to air pollution and the incidence of acute coronary events and stroke. DESIGN: closed cohort. SETTING AND PARTICIPANTS: subjects aged >=30 years, who took part in the 2011 census, residents in 5 cities (Turin, Bologna, Rome, Brindisi and Taranto). Annual concentrations of particulate matter (PM10 and PM2.5), nitrogen dioxide (NO2) and warm-season ozone (O3) (annual O3 in Taranto and Brindisi), estimated through satellite (Turin, Bologna, Rome) or photochemical models (Taranto and Brindisi) with a spatial resolution of 1 km2, were assigned to the census address. MAIN OUTCOME MEASURES: incidence of coronary heart disease (CHD) and stroke until 31.12.2018 (2019 in Bologna). Cohort-specific Hazard Ratios (HRs), estimated using Cox regression models progressively adjusting for individual and contextual covariates, were pooled with random-effect meta-analysis. RESULTS: there were 71,872 incident CHD cases and 43,884 incident cases of stroke in almost 18 million person-years. No association was observed between the exposures studied and incidence of CHD and stroke, except for an increase in the incidence of CHD associated with warm-season O3 exposure (HR 1.034 per 5 µg/m3 increase). Some positive associations were found in specific cities (both outcomes in Brindisi with PM10 exposure and in Taranto with NO2 exposure, stroke in Rome with both PM10 and PM2.5), although estimates were not significant in some instances. CONCLUSIONS: LMS are a high potential tool for the study of comparative medium- and long-term effects of air pollution. Their further development (different definitions of exposure, outcomes, characteristics of the urban areas and extension to other LMS) may make them even more valuable tools for monitoring and planning public health interventions.

[Long-term exposure to air pollution and natural mortality: variations related to the use of different exposure indicators in the cohorts of BIGEPI project]. / Esposizione di lungo periodo all'inquinamento atmosferico e mortalità naturale: variazioni legate all'utilizzo di diversi indicatori di esposizione nelle coorti del progetto BIGEPI.

OBJECTIVES: appropriate assessment of exposure to air pollution is crucial for the estimation of adverse effects on human health, both in the short and long term. Within the BIGEPI project, different indicators of long-term exposure to air pollution, in association with mortality by cause, were tested within the Italian longitudinal metropolitan studies (LMS). This allowed an evaluation of differences in effect estimates using the different exposure indicators. DESIGN: closed cohort. SETTING AND PARTICIPANTS: subjects aged >=30, who took part in the 2011 census, residents in 5 cities (Turin, Bologna, Rome, Brindisi and Taranto). MAIN OUTCOME MEASURES: at the time of enrolment, residential exposure levels to particulate matter <=10 µm (PM10), PM <=2.5 µm (PM2.5), nitrogen dioxide (NO2) and ozone (O3) for the period April-September (O3 warm season) were obtained from models at different spatial resolutions, from 1x1km to 200x200m (from the BEEP project) to 100x100m (ELAPSE project). In addition, locally developed models were used in each area (FARM photochemical model at 1x1-km for the cities of Rome, Taranto and Brindisi, Land-Use Regression (LUR) model for the city of Turin, PESCO model for Bologna). Cox proportional hazards models were applied to assess the association between exposure to air pollution (assessed using different exposure indicators) and natural mortality, adjusting for both individual and area covariates. RESULTS: the exposure levels derived by the different models varied between pollutants, with differences between the averages ranging from 3 to 20% for PM10, from 1 to 23% for PM2.5, and from 3 to 28% for NO2; the results for O3 were more heterogeneous. A total of 267,350 deaths from natural causes were observed. There is low heterogeneity in the effect estimates calculated from different environmental models, while there is greater variability in average exposure values, with different behaviour depending on the model and the characteristics of the area investigated. Differences are more pronounced where local risk factors are relevant, e.g., in industrial cities, thus suggesting the need of considering industrial exposure separately from other sources. CONCLUSIONS: the numerous heterogeneities in the data used make it difficult to draw conclusions about the comparisons studied. Nevertheless, this study suggests that different approaches to the assessment of environmental exposure should be evaluated depending on the national or local level of interest, also according to the specifities of the investigated areas.

[The Integrated Environmental Health Impact of emissions from a steel plant in Taranto and from a power plant in Brindisi, (Apulia Region, Southern Italy)]. / L'impatto ambientale e sanitario delle emissioni dell'impianto siderurgico di Taranto e della centrale termoelettrica di Brindisi.

OBJECTIVES: to estimate the environmental and health impact attributable to PM2.5 emissions from the ex-ILVA steel plant in Taranto and the ENEL power plant in Brindisi (Apulia Region, Southern Italy). DESIGN: a SPRAY Lagrangian dispersion model was used to estimate PM2.5 concentrations and population weighted exposures following the requirements of the Integrated Environmental Authorization (IEA) of the two plants under study. Available concentration-response functions (OMS/HRAPIE and updates) were used to estimate the number of attributable premature deaths. SETTING AND PARTICIPANTS: residents in the 40 municipalities of the domains of the VDS (assessment of health damage, according to the Regional Law n. 21/2012) of Brindisi (source: Italian National Institute of Statistics 2011 Census) and residents in Taranto, Statte, and Massafra (source: cohort study). MAIN OUTCOME MEASURES: mortality from natural causes, cardiovascular and respiratory diseases, and lung cancer attributable to PM2.5. Incremental lifetime cumulative risks (ILCRs) for lung cancer associated to PM2.5 exposure. RESULTS: there was a reduction of the estimated impacts from the pre to the post IEA-scenarios in both Taranto and Brindisi. In Taranto, ILCRs greater than 1x10-4; were estimated in 2010 and 2012; the ILCR was greater than 1x10-4; in the district of Tamburi (near the plant) also for the 2015 scenario. ILCRs estimated for Brindisi were between 1x10-6; and 4x10-5;. CONCLUSIONS: the Integrated Environmental Health Impact Assessment confirmed the results of the VDS conducted according to the toxicological risk assessment approach. An unacceptable risk was estimated for Tamburi also for the 2015 scenario, characterized by a production of 4.7 million tons of steel, about half compared to one foreseen by the IEA (8 mt.).

Non-occupational exposure to heavy metals of the residents of an industrial area and biomonitoring.

In areas at high environmental risk, a major issue is the assessment of the exposure of the general population to industrial pollutants. To date, few studies have investigated exposure to heavy metals in a population residing in a high risk environmental area. The aim of this study is to evaluate the exposure to heavy metals in the industrial area of Taranto, Southern Italy, through biological monitoring techniques. We measured the levels of inorganic arsenic and methylated metabolites, lead, cadmium, chromium, and manganese in the urine samples of 279 subjects residing in Taranto and neighboring areas. After obtaining informed consent from each participant, qualified health staff administered a standardized structured questionnaire investigating lifestyle habits and assessing any confounding factors. The biological monitoring data showed high urinary concentrations of nearly all of the heavy metals investigated. These findings could be related to the presence of industrial plants and is sufficient to warrant the expectation that local and national institutions should be required to adopt preventive measures to reduce the environmental exposure of the general population to heavy metals.

Hysteroscopy as a valid tool for endometrial pathology in patients with postmenopausal bleeding or asymptomatic patients with a thickened endometrium: hysteroscopic and histological results.

OBJECTIVE: This study compares hysteroscopic and histopathological results in postmenopausal women with abnormal uterine bleeding (AUB) and asymptomatic postmenopausal women with a thickened endometrium. MATERIALS AND METHODS: This is a retrospective study of 570 cases hysteroscopically examined between January 2008 and July 2012. The patients were followed up at the Istituto Tumori 'Giovanni Paolo II', Bari, Italy. RESULTS: A total of 320 of the 570 cases were selected. The inclusion criteria were transvaginal ultrasound, hysteroscopy and endometrial biopsy. In the AUB group, if the hysteroscopy results were normal, a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 100, 95, 71 and 100%, respectively, were achieved, while in the asymptomatic group these values were 100, 97, 90 and 100%, respectively. For both the group with polyps and that with myomas, the sensitivity, specificity, PPV and NPV were 100%. For endometrial hyperplasia, hysteroscopy showed a sensitivity, specificity, PPV and NPV of 81, 96, 87 and 93%, respectively, in the AUB group, while in the asymptomatic group, the sensitivity was 60%, the specificity and PPV were 100%, and the NPV was 98%. The sensitivity of hysteroscopy for endometrial cancer was 63%, the specificity 97%, the PPV 77%, and the NPV 95%. CONCLUSIONS: In postmenopausal women with a thickened endometrium with or without AUB, hysteroscopy allows for an accurate diagnosis in benign endometrial pathology. Hysteroscopy also allows directed biopsies of suspicious lesions, which is useful in malignant endometrial pathology.

Azacitidine in the front-line treatment of therapy-related myeloid neoplasms: a multicenter case series.

BACKGROUND/AIM: A continued increase in the incidence of therapy-related myeloid neoplasms (t-MN) is expected due to the improvement of chemotherapeutic treatments for solid and haematological malignancies. The use of 5-azacytidine (AZA) is emerging in these patients. We, therefore, analyzed the outcome of patients with t-MN ineligible for intensive chemotherapy treated in the front-line with AZA. PATIENTS AND METHODS: We retrospectively collected clinical data from consecutive patients with t-MN treated in the front-line with AZA at five Haematology Centers. Response to therapy, overall survival (OS) and safety were considered. RESULTS: The overall response rate was of 35.7% with a median OS of 9.6 months. Patients who were heavily pre-treated for their primary malignancy (more than 3 lines of chemotherapy) presented a significant inferior OS (4.9 months). The principal reported toxicity was haematological with severe infections occurring in a minority of patients. Fatigue was the most common extra-haematological toxicity. CONCLUSION: New aspects emerged on the management of t-MN. AZA may represent a reasonable choice for patients ineligible for intensive treatment, with the exception of heavily pre-treated patients who presented -anyway- a worse outcome.

Sorafenib and locoregional deep electro-hyperthermia in advanced hepatocellular carcinoma: A phase II study.

The standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib, a multikinase inhibitor of tumor cell proliferation and angiogenesis. Hyperthermia inhibits angiogenesis and promotes apoptosis. Potential synergic antiangiogenic and proapoptotic effects represent the rationale for combining sorafenib with electro-hyperthermia (EHY) in HCC. A total of 21 patients (median age, 64 years; range, 55-73 years) with advanced HCC were enrolled in the current study between February 2009 and September 2010. EHY was achieved by arranging capacitive electrodes with a deep hypothermia radiofrequency field of 13.56 Mhz at 80 W for 60 min, three times per week for six weeks, followed by two weeks without treatment, in combination with sorafenib at a dose of 800 mg every other day. According to the modified Response Evaluation Criteria in Solid Tumors criteria, 50% achieved stable disease, 5% achieved partial response and 45% achieved progressive disease. No complete response was observed. The progression-free survival (PFS) rate at six months was 38%, while the median PFS and overall survival times were 5.2 [95% confidence interval (CI), 4.2-6.2) and 10.4 (95% CI, 10-11) months, respectively. The overall incidence of treatment-related adverse events was 80%, predominantly of grade 1 or 2. Grade 3 toxicity included fatigue, diarrhea, hand-foot skin reaction and hypertension. In the present study, the sorafenib plus EHY combination was feasible and well tolerated, and no major complications were observed. The initial findings indicated that this combination offers a promising option for advanced HCC.

Estimates of cancer burden in Puglia.

AIMS AND BACKGROUND: A regional population-based cancer registry that provides incidence and survival data has become active only recently. Since it is important to know the time trends of basic epidemiological indicators to understand the cancer burden in the region, this paper will provide incidence, prevalence and mortality estimates in the region for seven major cancers for the period 1970-2015. METHODS: The estimates were obtained by applying the MIAMOD method, a statistical back-calculation approach to derive incidence and prevalence figures starting from mortality and relative survival data. Survival was modeled on the basis of published data from the Italian cancer registries. RESULTS: The incidence rates are estimated to be still increasing for female breast cancer, colorectal cancer in men and skin melanoma in both sexes. By contrast, the incidence rates indicate a decreasing trend for cervix uteri cancer and stomach cancer, the latter both in men and women. For these cancers an analogous trend is observed for mortality, confirming the reduction of the risk factors related to these cancer types. The incidence rates for lung cancer and prostate cancer in men were estimated to rise, reach a peak, and then decrease in the last part of the considered period. Prevalence increased for all the considered cancers except cervix cancer. The increase was striking for breast cancer and less pronounced for stomach cancer in both genders. CONCLUSION: This paper provides a description of the burden of the major cancers until 2015. The results highlight the need to reinforce effective preventive measures to contrast cancers related to an unhealthy lifestyle and to increase the compliance with organized screening programs to reduce the colorectal and breast cancer burden.

Changes in angiogenesis and hypoxia-inducible factor-1α protein expression in relapsed/refractory indolent non-Hodgkin lymphomas.

Angiogenesis is involved in the pathogenesis and progression of non-Hodgkin lymphomas (NHL), and hypoxia-inducible factor-1α (HIF-1α, also termed HIF1A) might contribute to this process. Currently, there is no direct evidence that the clinical progression of indolent NHL is associated with angiogenesis, and the expression of HIF-1α at recurrence is unknown. Matched lymph node biopsies at diagnosis and recurrence of relapsed/refractory indolent NHL patients were analysed by immunohistochemical and morphometric analysis. We observed an increased vascular network and HIF-1α protein expression in the second biopsy, providing direct evidence that angiogenesis is an essential process for disease progression.

[Health impact assessment of pollution from incinerator in Modugno (Bari)]. / Valutazione ex-ante dell'impatto sulla salute attribuibile all'inquinamento da inceneritore a Modugno (Bari).

OBJECTIVES: the purpose of this study is to assess the potential health impact of the start-up of a new incinerator in general population living near the facility in Modugno, province of Bari (Puglia Region, Italy), in combination with the existent Combined-Cycle combustion Gas Turbine (CCGT) power generation facility. DESIGN: an algorithm was used to calculate the number of cases (deaths and hospital admissions) associated with a given concentrations of PM10, the exposed population, the specific mortality/morbidity rate. For every health end-point, an estimate of RR was obtained from the literature. Using PM10 as tracer, simulations were made of incinerator emissions fallout. Residents within 2 km radius from the plants were considered. RESULTS: with the reduction of the average concentration of PM10 to 40 µg/m(3), 0.12% of natural causes of death could be prevented. Proportionally, the increment in PM10 concentration of 1 µg/m(3) could be associated to 0.02% of deaths. CONCLUSIONS: the estimated health impact of the incinerator emissions doesn't modify the epidemiological profile for the population living nearby.

Biomarkers in malignant mesothelioma: diagnostic and prognostic role of soluble mesothelin-related peptide.

Soluble mesothelin-related peptide (SMRP) is a biomarker that has been proposed for differential diagnosis from pleural metastatic cancer, as well as prognosis and treatment monitoring of malignant pleural mesothelioma (MM). The aim of this study was to evaluate the role of SMRP in clinic management of MM. We assayed the SMRP concentrations in 354 subjects: 109 healthy volunteers with no history of exposure to asbestos, 26 patients with previous occupational asbestos exposure but who were free from pleural or parenchymal disease, 48 patients with asbestosis, 110 patients with pleural plaques, 25 patients with lung cancer, and 36 patients with MM. We also tested SMRP titers in 2 patients with MM at 5 different times of the disease, to evaluate the trend of the biomarker in the course of therapy. Our data confirm previous experiences with the use of SMRP as a diagnostic marker of MM. Low SMRP levels at diagnosis seem to have a positive prognostic significance.