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Air pollution is a leading risk factor for global mortality and morbidity. Oxidative stress is a key mechanism underlying air-pollution-mediated health effects, especially in the pathogenesis/exacerbation of airway impairments. However, evidence lacks on subgroups at higher risk of developing more severe outcomes in response to air pollution. This multi-centre study aims to evaluate the association between air pollution and oxidative stress in healthy adults and in patients affected by airway diseases from the Italian GEIRD (Gene Environment Interactions in Respiratory Diseases) multi-case control study. Overall, 1841 adults (49 % females, 20-83 years) were included from four Italian centres: Pavia, Sassari, Turin, and Verona. Following a 2-stage screening process, we identified 1273 cases of asthma, chronic bronchitis, rhinitis, or COPD and 568 controls. Systemic oxidative stress was quantified by urinary 8-isoprostane and 8-OH-dG. Individual residential exposures to NO 2 , PM 10 , PM 2.5 , and O 3 were derived using an innovative five-stage machine-learning-based approach. Linear mixed regression models tested the association between oxidative stress biomarkers and air pollution tertiles, adjusting by age, sex, BMI, smoking, education and season, with recruiting centres as random intercept. Only cases exhibited higher levels of log-transformed 8-isoprostane and 8-OH-dG in association with NO 2 (β: 0.30 95 % CI: 0.08-0.52 and 0.20 95 % CI: 0.03-0.37), PM 10 (0.34 95 % CI: 0.12-0.55 and 0.21 95 % CI: 0.05-0.37) and PM 2.5 (0.27 95 % CI: 0.09-0.49 and 0.18 95 % CI: 0.02-0.34) as compared to the first tertile of exposure. No significant associations were observed for summer O 3 . Our findings suggest that exposure to air pollution may increase systemic oxidative stress levels in people suffering from airway diseases. This introduces a potential novel approach available for future epidemiological studies and Public Health for effective prevention strategies oriented at the quantification of early biological effects in susceptible people, whose additional risk level might be currently underrated. Air-pollution-mediated exacerbations, driven by oxidative stress, still deserve our attention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Long-term exposure to air pollution has adverse respiratory health effects. We investigated the cross-sectional relationship between residential exposure to air pollutants and the risk of suffering from chronic respiratory diseases in some Italian cities. In the BIGEPI project, we harmonised questionnaire data from two population-based studies conducted in 2007-2014. By combining self-reported diagnoses, symptoms and medication use, we identified cases of rhinitis (n = 965), asthma (n = 328), chronic bronchitis/chronic obstructive pulmonary disease (CB/COPD, n = 469), and controls (n = 2380) belonging to 13 cohorts from 8 Italian cities (Pavia, Turin, Verona, Terni, Pisa, Ancona, Palermo, Sassari). We derived mean residential concentrations of fine particulate matter (PM 10 , PM 2.5 ), nitrogen dioxide (NO 2 ), and summer ozone (O 3 ) for the period 2013-2015 using spatiotemporal models at a 1 km resolution. We fitted logistic regression models with controls as reference category, a random-intercept for cohort, and adjusting for sex, age, education, BMI, smoking, and climate. Mean ± SD exposures were 28.7 ± 6.0 μg/m 3 (PM 10 ), 20.1 ± 5.6 μg/m 3 (PM 2.5 ), 27.2 ± 9.7 μg/m 3 (NO 2 ), and 70.8 ± 4.2 μg/m 3 (summer O 3 ). The concentrations of PM 10 , PM 2.5 , and NO 2 were higher in Northern Italian cities. We found associations between PM exposure and rhinitis (PM 10 : OR 1.62, 95%CI: 1.19-2.20 and PM 2.5 : OR 1.80, 95%CI: 1.16-2.81, per 10 μg/m 3 ) and between NO 2 exposure and CB/COPD (OR 1.22, 95%CI: 1.07-1.38 per 10 μg/m 3 ), whereas asthma was not related to environmental exposures. Results remained consistent using different adjustment sets, including bi-pollutant models, and after excluding subjects who had changed residential address in the last 5 years. We found novel evidence of association between long-term PM exposure and increased risk of rhinitis, the chronic respiratory disease with the highest prevalence in the general population. Exposure to NO 2 , a pollutant characterised by strong oxidative properties, seems to affect mainly CB/COPD., Competing Interests: Declaration of competing interest Sara Maio reports financial support was provided by National Institute for Insurance against Accidents at Work., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: air pollution is a complex mixture; novel multipollutant approaches could help understanding the health effects of multiple concomitant exposures to air pollutants., Aim: to assess the relationship of long-term air pollution exposure with the prevalence of respiratory/allergic symptoms and diseases in an Italian multicenter study using single and multipollutant approaches., Methods: 14420 adults living in 6 Italian cities (Ancona, Pavia, Pisa, Sassari, Turin, Verona) were investigated in 2005-2011 within 11 different study cohorts. Questionnaire information about risk factors and health outcomes was collected. Machine learning derived mean annual concentrations of PM 10 , PM 2.5 , NO 2 and mean summer concentrations of O 3 (μg/m 3 ) at residential level (1-km resolution) were used for the period 2013-2015. The associations between the four pollutants and respiratory/allergic symptoms/diseases were assessed using two approaches: a) logistic regression models (single-pollutant models), b) principal component logistic regression models (multipollutant models). All the models were adjusted for age, sex, education level, smoking habits, season of interview, climatic index and included a random intercept for cohorts., Results: the three-year average (± standard deviation) pollutants concentrations at residential level were: 20.3 ± 6.8 μg/m 3 for PM 2.5 , 29.2 ± 7.0 μg/m 3 for PM 10 , 28.0 ± 11.2 μg/m 3 for NO 2 , and 70.9 ± 4.3 μg/m 3 for summer O 3. Through the multipollutant models the following associations emerged: PM 10 and PM 2.5 were related to 14-25% increased odds of rhinitis, 23-34% of asthma and 30-33% of night awakening; NO 2 was related to 6-9% increased odds of rhinitis, 7-8% of asthma and 12% of night awakening; O 3 was associated with 37% increased odds of asthma attacks. Overall, the Odds Ratios estimated through the multipollutant models were attenuated when compared to those of the single-pollutant models., Conclusions: this study enabled to obtain new information about the health effects of air pollution on respiratory/allergic outcomes in adults, applying innovative methods for exposure assessment and multipollutant analyses., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maria Beatrice Bilò had speaking and lecture fees supported by Astra Zeneca, GSK, Novartis, Sanofi. The other authors have no competing financial interests or personal relationships to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The aim of this project was to evaluate the current practice of D2 in Europe., Materials and Methods: In the first part of the study, 18 European high volume gastric cancer centres completed a questionnaire, designed to evaluate their preferred lymphadenectomy in a series of clinical scenarios. Surgeon compliance with international guidelines for lymphadenectomy was evaluated. In the second part, information on 381 gastrectomies performed for primary gastric cancer by participating surgeons from January to December 2015, was retrospectively collected., Results: Surgical choice in clinical scenarios was affected by tumour stage and to a lesser extent, site and histotype. In particular, in early gastric cancer with diffuse histology D2 was recommended by >70% of surgeons, while this percentage dropped to 44% in intestinal histotypes. When surgeons selected a D2 dissection, the procedure was rarely fully compliant with the Japanese guidelines. In the review of gastrectomy experience an adequate number of nodes (≥15 nodes) was retrieved in 97% after D2. The number of retrieved nodes varied with median values ranging from 17 to 35 (p < 0.001) after D2. D2/D2+ was more frequently performed in mixed (80%) and diffuse (78%) cases than in intestinal cases (69%) (p = 0.016)., Conclusions: Although an adequate lymphadenectomy was achieved in almost all cases in dedicated centres, there is still variation in the number of retrieved nodes. Tumor histology largely affects surgeon's choice as regards the extent of lymphadenectomy; however, the role of histology in planning surgical procedures needs to be verified in prospective trials., Competing Interests: Declaration of competing interest All the Authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Prophylactic drain in gastrectomy for cancer is still widely used, although some evidence has disputed this practice and spreading enhanced recovery protocol has been pushing towards surgical simplification. This study aimed at assessing the impact of drain placement on important clinical outcomes, evaluating the results of randomised controlled trials (RCTs), or cohort studies whenever information provided by the former was scarce. PubMed, PMC, Cochrane Library, CNKI and Wanfang databases were searched from January 1990 to February 2019, both for RCTs and cohort studies comparing use or avoidance of prophylactic drain in gastric cancer patients undergoing gastrectomy. All RCTs and cohort studies were rated according to Jadad score and Newcastle-Ottawa-Scale, respectively. Meta-analysis was separately performed on RCTs and cohort studies. The following clinical outcomes were considered: anastomotic leak, reoperation rate, additional drain procedure, length of stay, postoperative morbidity, postoperative mortality, readmission rate and drain related complications. Overall, 3 RCTs (330 patients) and 7 cohort studies (2897 patients) were included. Seven studies came from Eastern Countries. Meta-analysis on RCTs evidenced that drain avoidance halves overall morbidity (RR = 0.47, 95%CI 0.26-0.86, p = 0.014) and slightly reduces length of stay (SMD -0.24, 95%CI -0.51-0.03, p = 0.083). Only one postoperative death occurred in the drain group. The other outcomes were either not reported or reported just by one RCT each. Meta-analysis on cohort studies, despite higher statistical power, did not highlight any significant difference. This meta-analysis showed that prophylactic drain avoidance can reduce morbidity and length of stay, while not significantly affecting other major surgical outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Although many studies have highlighted the link between asthma/rhinitis and depression, it is still unclear which characteristics of these diseases are associated with the risk of depression. We aimed to explore the relationship between depression and asthma or rhinitis in a representative sample of the Italian general population., Methods: The data were collected in GEIRD, an Italian multicenter, population-based, multicase-control study. 2227 participants (age 21-86 years, female 50%) underwent standardized interviews, skin prick and lung function tests, and were divided into cases of current asthma (n = 528), rhinitis without asthma (n = 972), and controls (n = 727). Two specific questions from the Patient Health Questionnaire (PHQ-2) were asked to identify symptoms of depressed mood and anhedonia, which were used as a proxy of major depression disorder., Results: The prevalence of depression was 16.7%, 11.9%, and 5.1% in subjects with asthma, rhinitis and controls, respectively. Both in asthma and rhinitis, subjects with depression had worse respiratory-health related quality of life and more frequent disease-related symptoms than their non-depressed counterparts. In asthma, depression was associated with poorer disease control. In rhinitis, depression was significantly associated with a disease-related limitations in daily activities and greater risk of symptom exacerbations and prescriptions of medicines for breathing. Cases of rhinitis with depression were less likely to be atopic., Conclusions: Our results suggest that rhinitis exacerbations, particularly in non-atopic subjects, and low asthma control are strongly related to the presence of depressed mood in adults from the general population., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Phytosterols in vegetable oil (VO)-based lipid emulsions (LE) likely contribute to parenteral nutrition-associated cholestasis (PNAC) in preterm infants. No characterization of plasma phytosterol half-lives has been done in very low birth weight (VLBW) preterm infants receiving parenteral nutrition (PN) with LE., Methods: In a prospective cohort study, 45 VLBW preterm infants who received PN underwent serial blood sample measurements of sitosterol (SITO), campesterol (CAMP), and stigmasterol (STIGM). Plasma phytosterol half-lives were calculated from the phytosterol concentrations-decay curves by using a single-compartment model., Results: After the stop of the intravenous LE, study infants had significantly lower plasma total CAMP, STIGM and SITO concentrations. The decay of plasma phytosterol concentrations was monoexponential. Half-life of plasma total CAMP, STIGM and SITO was 13.5 ± 6.9, 10.3 ± 4.5 and 10.3 ± 4.0 days, respectively. Plasma phytosterol half-lives did not correlate with gestational age, birth weight, cumulative phytosterol intakes and plasma conjugated bilirubin., Conclusion: VLBW preterm infants on PN with LE had rather long plasma phytosterol half-lives similar to hypercholesterolemic adults and phytosterolemic homozygotes patients. We speculate that the accumulation of phytosterols could contribute to their vulnerability to PNAC., Clinical Trial Registry: The Ethics Committee of Marche-Italy (DG/469); www.clinicaltrials.gov (identification number NCT02758834)., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Pollen exposure has acute adverse effects on sensitized individuals. Information on the prevalence of respiratory diseases in areas with different pollen concentrations is scanty., Aim: We performed an ecologic analysis to assess whether the prevalence of allergic rhinitis and asthma in young adults varied across areas with different pollen concentrations in Italy., Methods: A questionnaire on respiratory diseases was delivered to random samples of 20-44year-old subjects from six centers in 2005-2010. Data on the daily air concentrations of 7 major allergologic pollens (Poaceae, Urticaceae, Oleaceae, Cupressaceae, Coryloideae, Betula and Ambrosia) were collected for 2007-2008. Center-specific pollen exposure indicators were calculated, including the average number of days per year with pollens above the low or high concentration thresholds defined by the Italian Association of Aerobiology. Associations between pollen exposure and disease prevalence, adjusted for potential confounders, were estimated using logistic regression models with center as a random-intercept., Results: Overall, 8834 subjects (56.8%) filled in the questionnaire. Allergic rhinitis was significantly less frequent in the centers with longer periods with high concentrations of at least one (OR per 10days=0.989, 95%CI: 0.979-0.999) or at least two pollens (OR=0.974, 95%CI: 0.951-0.998); associations with the number of days with at least one (OR=0.988, 95%CI: 0.972-1.004) or at least two (OR=0.985, 95%CI: 0.970-1.001) pollens above the low thresholds were borderline significant. Asthma prevalence was not associated with pollen concentrations., Conclusions: Our study does not support that the prevalence of allergic rhinitis and asthma is greater in centers with higher pollen concentrations. It is not clear whether the observed ecologic associations hold at the individual level., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: In gastric cancer the incidence of loco-regional recurrences decreases when lymphadenectomy is expanded from D1 to D2. The present study aimed at evaluating whether the pattern of recurrence in advanced gastric cancer (AGC) is further modified when lymphadenectomy is expanded from D2 to D3., Methods: 568 patients undergoing curative gastrectomy for AGC (274 D2 and 294 D3) were considered; none of them received preoperative chemotherapy. MantelHaenszel test of homogeneity was used to verify whether the relation between extension of lymphadenectomy and recurrence varied as a function of each risk factor considered. The impact of D2 and D3 on relapse was further investigated by multivariable logistic regression model., Results: Cumulative incidence of recurrence did not significantly differ after D2 and after D3 in the whole series (45.3% vs 46.3%; p = 0.866). However, the association between recurrence and extension of lymphadenectomy was significantly affected by histology (Mantel-Haenszel test of homogeneity: p = 0.007). The risk of recurrence was higher after D3 than after D2 (45.1% vs 35.3%) in the intestinal histotype while the pattern was reversed in the mixed/diffuse histotype (48.3% vs 61.5%). This pattern was confirmed in multivariable logistic regression: the interaction between histology and extension of lymphadenectomy was highly significant (p = 0.004). In particular, cumulative incidence of locoregional recurrences was higher in the diffuse histotype after D2, while being higher in the intestinal histotype after D3., Conclusions: D3 reverses the negative impact of diffuse histotype on relapses, especially on locoregional recurrences. Therefore D3 could be considered a valid therapeutic option in histotype-oriented tailored treatment of AGC., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Formaldehyde (FA) is a suspected human carcinogen capable of inducing oxidative stress through different metabolic ways. FA may originate from tobacco smoke, several environmental sources, as well as occupational sources, like furnishing industries specialized in the production of pressed-wood and laminate products., Object: Our aim was to investigate the role of tobacco smoke and occupational exposure to air-FA in the induction of oxidative stress status by comparing FA-exposed with non-exposed subjects who smoked or did not., Methods: Enrollment of 105 subjects was made in an industry of plastic laminates, including both workers directly exposed to FA and non-exposed office personnel, as control group. 15-F(2t) isoprostane (15-F(2t) IsoP), detected by ELISA technique and urinary cotinine, detected by GC-MS, were used for evaluating oxidative stress and tobacco smoke exposure, respectively. Air-FA levels were detected by GC-MS., Results: FA concentrations were significantly higher in subjects occupationally exposed than the controls. Smoking habits and air-FA exposures independently induce the formation of 15-F(2t) IsoP and increase the oxidative stress level., Conclusions: Our findings show, for the first time, that 15-F(2t) IsoP presents a dependency from both the smoking habit and air-FA exposures, and consequently, that these breathable pollutants could be considered as two important independent risk factors in increasing the oxidative stress in human beings., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: The association between smoking habits and asthma is complex because subjects with asthma could avoid smoking, whereas smoking could increase asthma severity or incidence., Purpose: The relation between asthma in childhood (0-10 years) and smoking initiation in the second decade (11-20 years) was investigated using the database of the Italian Study on Asthma in Young Adults, performed in 1998-2000 on people aged 20-45 years., Methods: The cumulative incidence of smoking initiation was compared among (1) subjects not reporting asthma attacks in the first 20 years of life (n = 17,384), (2) subjects reporting asthma onset in the first decade and no disease remission by the age of 20 years (n = 305), (3) subjects reporting asthma onset in the first decade and remission in the first and second decades (n = 573)., Results: Among men, the cumulative incidence of smoking onset was higher among nonasthmatics (49%) than among asthmatics (35.6%), and intermediate among asthmatics with disease remission (44.2%) (p = .001). These differences were larger in males born between 1953 and 1965, and tended to decrease in males born between 1966 and 1979: cumulative incidence of smoking onset decreased from 54.3% to 43.8% in nonasthmatics, whereas it remained stable in asthmatics (from 36.8% to 35%). Women, instead, had similar cumulative incidence of smoking initiation, irrespective of asthma onset or remission (p = .849)., Conclusion: Asthma in childhood reduces smoking initiation during the subsequent teenage in men, but not in women. This protective effect tends to fade when asthma remission occurs. In the last decades, smoking initiation has decreased among nonasthmatic males, but not among asthmatic males., (Copyright © 2011 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Rationale and Objectives: Response to mailed epidemiological surveys has decreased in recent decades. Since subjects with respiratory symptoms are usually early responders to surveys performed in Southern Europe, this trend could bias prevalence estimates. The present study aimed at evaluating the impact of non-response bias on prevalence estimates of respiratory symptoms and smoking habits., Methods: In 9 centres, participating in the Italian Study on Asthma in Young Adults (ISAYA), random samples of people aged 20-45 years were administered a mailed questionnaire between 1998 and 2000. Non-responders were contacted again first by mail and then by phone. Cumulative response percentage was 30.5%, 52.4% and 72.7% (18,873/25,969), respectively, after the 1st, 2nd and 3rd contact., Results: The prevalence of self-reported current asthma, asthma-like symptoms, and chronic cough/phlegm was more than halved from the first contact (5.6%, 17.8%, 14.6% respectively) to the third contact (2.7%, 6.4%, 6.9%). This pattern was less pronounced when considering allergic rhinitis and past asthma, whose prevalence decreased, respectively, from 21.5% to 15.6% and from 3.5% to 2.6%. At the same time the proportion of current smokers increased from 29.2% to 38%, while the proportion of ex-smokers decreased from 16.5% to 10.1%. In a multinomial logistic model current asthma, asthma-like symptoms, chronic cough/phlegm and smoking habits, and to a lower extent past asthma and allergic rhinitis, were significant predictors of late response., Conclusions: In Italy when response percentage is low, the prevalence of current asthma, chronic cough/phlegm and ex-smokers is overestimated, while the proportion of current smokers is underestimated.

Background: Monitoring adverse events during chemotherapy by clinicians is a standard practice but clinicians may report fewer side-effects or lower symptom severity than patients. Our aim was to compare symptoms self-reported by patients with symptoms registered by clinicians and nurses, to assess validity of a nurse reporting., Methods: From April to August 2007, a double-blind questionnaire with 13 common items graduated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events was completed by clinicians and nurses for outpatients undergoing chemotherapy at our Medical Oncology Day Hospital Unit. Patients completed a modified questionnaire with simplified terms. They were requested to specify seriousness of symptoms with a subjective scale varying from 1 to 4. Every patient-nurse-clinician questionnaire was registered for the statistical analysis. Agreement was evaluated by Cohen's kappa coefficient., Results: Eighty-five paired questionnaires were completed. Patients, nurses and clinicians agreed on most symptoms and toxicity grade. Agreements between patients and nurses were stronger than those between patients and physicians for the six most common symptoms: asthenia (kappa 75% versus 37%), constipation (83% versus 45%), neuropathy (82% versus 55%), mucositis (78% versus 46%) and diarrhoea (90% versus 77%). These differences mainly reflected differences in the proportion of positive agreement: nurses were more able to detect symptoms self-reported by patients than physicians. The only exception was nausea, as kappa coefficient was very good for both health professionals (91% versus 89%). When considering the different grade of toxicity by the weighted kappa coefficient, we scored again the highest agreement between patient and nurse, with weighted kappa ranging from 55% (asthenia) to 86% (diarrhoea), and the lowest agreement between patient and physician, with weighted kappa ranging from 32% (asthenia) to 74% (nausea). The agreement between physician and nurse slightly improved, with weighted kappa ranging from 41% (constipation) to 77% (nausea)., Conclusion: Our results support the validity of nurse toxicity reporting and that the nurse staff could be successfully employed in collecting toxicity data because of a greater ability to elicit information from patients than the medical staff.

Our objective was to study the metabolic precursors of surfactant disaturated-phosphatidylcholine (DSPC) in preterm infants with respiratory distress syndrome (RDS) on mechanical ventilation. We performed 46 DSPC kinetic studies in 23 preterms on fat-free parenteral nutrition and mechanical ventilation (birth weight = 1167 +/- 451 g, gestational age = 28.5 +/- 2.0 weeks). Eight infants received a simultaneous intravenous infusion of U(13)C-glucose and [16,16,16](2)H-palmitate, eight infants received U(13)C-glucose and (2)H(2)O, and seven received U(13)C-palmitate and (2)H(2)O. Surfactant DSPC kinetics were calculated from the isotopic enrichments of DSPC-palmitate from sequential tracheal aspirates and its metabolic precursors in plasma or urine. DSPC fractional synthesis rate (FSR) was 17 +/- 11, 21 +/- 16, and 15 +/- 6%/day from glucose, palmitate, and body water, respectively (P = 0.36). DSPC-FSR from U(13)C-glucose and (2)H(2)O were significantly correlated and yielded similar estimates (difference of -0.1 +/- 3%) (P = 0.91). The difference in the 15 infants receiving palmitate versus (2)H(2)O or palmitate versus glucose was +6.0 +/- 12%/day (P = 0.21). There was a significant correlation between DSPC-FSRs from plasma glucose and plasma FFA. The contribution of glucose versus palmitate to DSPC-FSR was 49 +/- 20% versus 51 +/- 20%, respectively. Plasma glucose and FFA showed similar contributions to DSPC-FSR in infants with RDS and fat-free parenteral nutrition. FSRs from (2)H(2)O or glucose were highly correlated.

Aims: Fasting plasma glucose variability strongly predicts the incidence of cardiovascular events in type 2 diabetic patients. We prospectively assessed whether fasting plasma glucose variability predicts the development/progression of retinopathy in a large cohort of type 2 diabetic outpatients., Methods: In the period 1996-1999, 1019 type 2 diabetic participants (aged 69+/-11 years) in the Verona Diabetes Study underwent at least 3 fasting plasma glucose (FPG) determinations and an eye examination by retinography. Of these, 746 underwent a 2nd eye examination in the period 2000-2004, while 273 did not (102 patients had died before undergoing the 2nd eye examination). For each patient, the mean (M-FPG) and the coefficient of variation of FPG (CV-FPG) were computed., Results: By the 2nd eye examination, 124 patients had either developed new retinopathy (79 patients) or progressed to a more severe degree of retinopathy (45 patients). In a multivariable logistic regression analysis, the development/progression of retinopathy was independently predicted by average glycaemia over time, expressed as glycated haemoglobin (odds ratio [OR] 1.82, 95%CI 1.40-2.38 for 1 SD increase) or M-FPG (OR 1.88, 1.47-2.41), but not by CV-FPG. Among other independent variables, HDL-cholesterol was inversely associated with the development/progression of retinopathy., Conclusions: These results suggest that in elderly type 2 diabetic patients the magnitude of hyperglycaemia, but not fasting plasma glucose variability, strongly predicts the development/progression of diabetic retinopathy independently of other known risk factors.

Background: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are long-chain polyunsaturated fatty acids (LCPs) that play pivotal roles in growth and neurodevelopment., Objective: We aimed to quantify the synthesis of LCPs in preterm infants fed infant formula containing LCPs., Design: Twenty-two preterm infants were randomly assigned to either the no-LCP group (fed formula without LCPs; n = 11) or the LCP group (fed formula with LCPs; n = 11). Dietary LCPs had higher (13)C content than did the endogenously synthesized LCPs, which were derived from linoleic and alpha-linolenic acids. The (13)C content of major selected plasma fatty acids was measured by using gas chromatography-isotope ratio mass spectrometry at birth and at age 1, 3, and 7 mo. Absolute LCP synthesis and the percentage of LCP synthesis relative to dietary intake were calculated., Results: Percentage AA synthesis was 67.2 +/- 7.8%, 35.9 +/- 9.8%, and 29.0 +/- 10.3%, and that of DHA was 41.7 +/- 14.9%, 10.5 +/- 8.1%, and 7.4 +/- 6.2% at 1, 3, and 7 mo old, respectively. Absolute AA synthesis was 26.7 +/- 4.2, 14.4 +/- 3.9, and 11.6 +/- 4.1 mg x kg(-1) x d(-1) and that of DHA was 12.6 +/- 4.5, 3.2 +/- 2.5, and 2.3 +/- 1.9 mg x kg(-1) . d(-1) at 1, 3, and 7 mo old, respectively. AA and DHA synthesis decreased significantly (P < 0.01) with time, and AA synthesis was significantly (P < 0.01) greater than DHA synthesis., Conclusions: By this novel approach, we measured endogenous LCP synthesis in infants receiving dietary LCPs over long periods. By age 7 mo, LCP synthesis was dramatically lower in preterm infants fed LCPs.

The aim of this study is to find and test a predictive model that could be suitable to estimate the outdoor NO(2) concentrations at individual level, by integrating ecological measurements recorded by local monitoring stations with individual information collected by a questionnaire. For this purpose, the data from the Italian centres of the European Community Respiratory Health Survey II (ECRHS II) has been used. Outdoor NO(2) concentrations were measured using NO(2) passive sampling tubes (PS-NO(2)), exposed outdoor for 14 days, between January 2001 and January 2003. Simultaneously, average NO(2) concentrations were collected from all the monitoring stations of the three centres (MS-NO(2)). Individual measurements carried out with passive samplers were compared with the corresponding NO(2) 2-week concentrations obtained as the average of all local (background and traffic) monitoring stations (MS-NO(2)). A multiple linear regression model was fitted to the data using the 2-week PS-NO(2) concentrations as the response variable and questionnaire information and MS-NO(2) concentrations as predictors. The model minimizing the root mean square error (RMSE), obtained from a ten-fold cross validation, was selected. The model with the best predictive ability included centre, season of the survey, MS-NO(2) concentrations, type and age of building, residential area and reported intensity of heavy-duty traffic and explained the 68.9% of the variance. The non-parametric correlation between PS-NO(2) and the concentrations estimated by the model is 0.81 (95% CI: 0.77-0.85). This study shows that over short periods (2 weeks) a good prediction of home outdoor exposure to NO(2) can be achieved by simply combining routinely collected ecological data with dwelling characteristics and self-reported intensity of heavy traffic. Further studies are needed to extend this prediction to long-term exposure.

Background: In most developed countries the prevalence of smoking habits is decreasing in men, while in women the prevalence seems to decline in Northern Europe but to increase in the Mediterranean area. The present research aims at assessing time trends in smoking habits in Italy., Methods: In the frame of the Italian Study on Asthma in Young Adults (ISAYA) a random sample of the Italian population aged 20-45 years was administered a mailed questionnaire in 9 Italian centers between 1998 and 2000. Cumulative response was 72.7% (18873/25969). Kaplan-Meier survival curves and log-rank test were used to compare probability of remaining a life-time non-smoker across birth cohorts (1953-58, 1959-63, 1964-68, 1969-73, 1974-78). Probability to quit smoking was also evaluated among ever-smokers., Results: Probability to persist as a non-smoker significantly increased across subsequent generations in both sexes. At the age of 20 years this probability amounted to 41.7% (95% CI 39.4-44.0%) in men and 52.7% (50.4-54.9%) in women born between 1953 and 1958, and it increased to 57% (54.8-59.1%) in men and 68.7% (66.6-70.7%) in women born in 1969-73, but no further decline in smoking habits was observed in the next birth cohort (1974-78). Also the probability to quit smoking significantly increased from the 1953-58 birth cohort to the 1969-73 one., Conclusions: Smoking has declined among Italian young adults of both genders. Further efforts are necessary to promote active anti-smoking campaign, especially among adolescents, which are at higher risk of starting to smoke.

Recently, the Rhesus D-negative phenotype was identified in multivariate analysis as an important independent risk factor in gastric cancer patients who underwent curative resection. The distribution of Rhesus (Rh) D phenotype was investigated in a group of 268 patients who underwent gastrectomy for gastric cancer from June 1988 to April 1999. After excluding patients with short, potentially guaranteed follow-up or who deceased in the postoperative period, the prognostic significance of Rh D phenotype was evaluated in a subgroup of 239 patients by Cox regression model controlling for gender, age, site, histology, depth of tumor invasion (T), node metastasis (N), and type of resection (R). Two hundred and thirty-six patients (88.1%) presented an Rh+ phenotype and 32 (11.9%) presented an Rh- phenotype. A significant association was found between Rh D- phenotype and the presence of residual tumor after surgery (P = .01). The cumulative 5-year survival rate (95% confidence interval) was 37.3% (18.1-56.6) in patients with Rh- phenotype and 47.0% (39.2-54.4) in patients with Rh+ phenotype. The Rh D phenotype did not affect survival independently either in univariate analysis (P = .27) or in multivariate analysis (P = .55). The relative risk of death in D-negative versus D-positive patients decreased from 1.36 (95% confidence interval, 0.80-2.30) in univariate analysis to 0.84 (0.47-1.49) in multivariate analysis after controlling for depth of tumor invasion, lymph node metastases, and type of resection. Our study did not confirm the prognostic significance of Rh D phenotype in gastric cancer patients.

Background: Immunocytochemistry has been proven able to identify tumor cells in bone marrow aspirate (BMA) of patients with SCLC. However, few data exist about the clinical significance of the procedure., Patients and Methods: 108 BMA taken from 60 patients were incubated with the MoAb MLuC1 (cluster 6) and stained by the APAAP (alkaline phosphatase-antialkaline phosphatase) method. The serum levels of LDH, TPA, NSE and CEA were also studied in relation to bone marrow involvement by means of discriminant analysis., Results: Immunocytochemistry of the aspirate with MLuC1 detected positive cells in 23 patients (38%) (38 of 108 samples) vs. 13% of the conventional biopsies studied without MLuC1 (P < 0.001). With respect to bone marrow positivity, three groups of patients were identified: those with no positive cells in the aspirate and negative biopsy (group A); those with less than 10 positive cells in the aspirate and negative biopsy (group B); and those with more than 10 positive cells or clumps in the aspirate or positive biopsy (group C). Group C patients had poorer median survivals than those in the other two groups (5.5 vs. 11 months, respectively, P = 0.01). Discriminant analysis showed that the four serum markers were poor discriminators of the degree of bone marrow involvement, with only 55% of grouped cases being correctly classified., Conclusions: These results show that detection of bone marrow involvement i) can be improved by the use of MLuC1 ii) is not predictable by conventional tumor markers, and iii) is related to poor outcome.

The aims of this study are: (1) to evaluate whether the estimates of the association of risk factors with bronchial hyperresponsiveness (BHR) depends on the accumulated dose administered in challenge tests; and (2) to verify whether a model developed for survival studies (Weibull regression) is suited to analyze methacholine dose-response curves. For these purposes, 863 challenge tests, from EC Respiratory Health Survey in Italy, up to a cumulative dose of 6 mg methacholine, were analyzed by Weibull regression and by traditional methods (logistic model and linear model), both before and after truncation of the curves at 2 mg. With all methods the main risk factors for BHR were respiratory symptoms and atopy while age and airway caliber exerted a protective action. Our results confirmed that in epidemiological surveys 2 mg methacholine is enough to fully appreciate the effect of risk factors on BHR and showed that the Weibull model explains the observed variability better than linear and logistic regressions.

The importance of long-chain polyunsaturated fatty acids (LCPs) in the development of preterm infants is now well accepted but the source of dietary LCPs to be added to infant formulas remains controversial. We measured dietary intakes, fecal output, and percentages of intestinal absorption of n-6 and n-3 LCPs in healthy preterm infants fed exclusively preterm breast milk (PBM; n = 20), formula without LCPs added (NLCPs; n = 19), formula with LCPs derived from phospholipids (PL-LCPs; n = 19), or formula with LCPs from triacylglycerols (TG-LCPs; n = 19). Intestinal absorption of arachidonic acid was not different in the four groups but docosahexaenoic acid was better absorbed from PL-LCPs than from PBM (88.3 +/- 1.8% compared with 78.4 +/- 4.0%, P < 0.05) Total absorption of n-6 LCPs was not different between groups but total n-3 LCPs were better absorbed from PL-LCPs than from PBM or TG-LCPs (88.7 +/- 1.9%, 79.2 +/- 4.4%, and 80.4 +/- 2.2%, respectively). In conclusion, docosahexaenoic acid and arachidonic acid were absorbed as efficiently from TG-LCPs formula as from breast milk fat. Absorption of docosahexaenoic acid and n-3 LCPs was greater from PL-LCPs formula than from PBM or TG-LCPs formula.

Purpose: Aggressive treatment has improved the long-term outcome of extremely low birth weight (ELBW) and low birth weight (LBW) neonates, but it has also increased the risk of iatrogenic lesions. The aim of this paper is to evaluate the incidence of vascular injuries observed in the neonatal intensive care unit of our hospital., Methods: From 1987 to 1994, 2898 neonates were admitted to the neonatal intensive care unit; 335 of them were either LBW or ELBW (11.5%). A review of the charts of these neonates disclosed nine neonates (four male, five female) with vascular lesions (2.6%); the mean gestational age of these patients was 28.7 weeks (range, 24 to 33 weeks), the mean weight at birth was 880 g (range, 590 to 1450 g), and the mean weight at diagnosis was 1825 g (range, 1230 to 2700 g). In the same period, 10 neonates with vascular injuries were reported in the 2563 neonates who weighed more than 1500 g (0.3%). The injuries observed in LBW and ELBW group were arteriovenous fistulas (two bilateral) at the femoral level (six neonates), carotid lesion (one neonate), and limb ischemia (two neonates). Injury was associated with venipuncture in seven neonates, and with umbilical catheter in one; the case of carotid lesion was related to surgical error. No general symptoms were observed., Results: The carotid lesion and five arteriovenous fistulas were repaired by microsurgical techniques; one case of limb ischemia was resolved with thrombolytic drugs, whereas an amputation at the knee level was required in the other after 10 days of medical treatment. One neonate with an arteriovenous fistula was just observed according to the parents' wishes. At clinical and echo-color Doppler follow-up, seven of nine neonates had normal vascular function without sequelae., Conclusions: In our experience, LBW and ELBW neonates are at greater risk than older neonates of the development of iatrogenic vascular lesions. We advocate aggressive microsurgery, medical treatment, or both to obtain good results and prevent late sequelae.

Limited information is available on the metabolic fate of medium-chain triacylglycerols (triglycerides) after intestinal absorption and on their influence on essential fatty acid metabolism. We studied in preterm infants the effect of two infant formulas, one with a high (HMCT) and one with a low (LMCT) medium-chain triacylglycerol content, on plasma fatty acids. The HMCT formula contained 46 mol% 8:0 + 10:0 and the LMCT formula (4.8 mol% 8:0 + 10:0) had approximately twice the amount of long-chain saturated and monounsaturated fatty acids as the HMCT. Both formulas had similar contents of linoleic and linolenic acids. Plasma lipids and fatty acids were determined at birth and on day 24 of life in 20 infants fed the LMCT (n = 12) or HMCT (n = 8) formula. Significant amounts of medium-chain fatty acids were found in the systemic circulation of the infants fed the HMCT formula, mainly in plasma fatty acids and triacylglycerols. Despite striking dietary differences, palmitic and stearic acids were not different between groups, indicating de novo synthesis of long-chain fatty acids with the HMCT formula. Plasma phospholipid docosahexaenoic acid was significantly lower in the HMCT group than in the LMCT infants (1.38 +/- 0.07 compared with 1.73 +/- 0.07 mol%, P = 0.002). Our data indicate that a high MCT intake in preterm infants increases lipogenesis, and dietary nonessential fatty acids interfere with the metabolism of docosahexaenoic acid.