A 5-Year Follow-Up of a Cohort of Italian Alcoholics: Hospital Admissions and Overall Survival.

BACKGROUND: Alcohol use disorders (AUDs), including alcohol dependence and alcohol abuse defined according to specific DSM-IV and ICD-10 criteria, can be potentially lethal, because they are associated with several medical and psychiatric conditions. This study aimed to describe the causes of hospitalization of a large cohort of subjects with alcohol dependence (alcoholics) enrolled in Florence (Italy) over a 5-year follow-up period and to evaluate the effect of hospitalization on overall survival. METHODS: One thousand one hundred and thirty alcoholics, newly diagnosed from 1997 to 2001, were linked to the Regional Mortality Registry for update of vital status as of December 31, 2006, and to the Hospital Discharge electronic archives of the Regional Health System of Tuscany to verify hospital admissions (HAs) during the 5-year postcohort enrollment follow-up. Kaplan-Meier survival and Cox regression analyses were performed to evaluate any association of HA with overall survival. RESULTS: A total of 3,916 new hospitalizations occurred during the 5-year follow-up. Most alcoholics (70.6%) reported at least 1 new hospitalization, with a first hospitalization rate of 61.7 per 100 person-years in the first year of follow-up. The mean number of hospitalizations per admitted subject was 4.87 (SD 7.4), and mean length of hospital stay was 8.5 days (SD 11.3). The main causes of hospitalization were mental disorders and diseases of the digestive system, as well as accidents or violence. Among those alcoholics alive after 1 year of follow-up, a significantly increased risk of dying in the following years could be predicted by early hospitalization in the 12 months preceding (hazard ratio [HR] 1.73; 95% confidence interval [CI] 1.15 to 2.60) or following (HR 3.59; 95% CI 2.31 to 5.61) enrollment in the cohort. CONCLUSIONS: Our results confirm the association of AUDs with several serious medical conditions. This fact may be responsible for a high impact on health resource utilization and high social costs. Early hospitalization significantly predicts vital status at 5 years.

Total and cancer mortality in a cohort of ulcerative colitis and Crohn's disease patients: The Florence inflammatory bowel disease study, 1978-2010.

BACKGROUND: There is no consensus on the leading causes of death among inflammatory bowel diseases (IBD) patients. AIM: We present the results of an extended follow-up of the population-based Florence IBD cohort, including 689 ulcerative colitis and 231 Crohn's disease patients. METHODS: The causes of death of cohort members were determined through linkage with the local mortality registry. We calculated standardized mortality ratios (SMR) and 95% confidence intervals (95%CI) by applying gender-, age- and calendar time-death rates to person-years at risk. RESULTS: Ulcerative colitis patients had overall mortality comparable to the general population (SMR 0.99, 95%CI 0.85-1.14), though being at increased risk of dying from Hodgkin's disease (SMR 11.74, 95%CI 2.94-46.94), rectal cancer (SMR 3.69, 95%CI 1.66-8.22) and Alzheimer's disease (2.40, 95%CI 1.00-5.76). Crohn's disease patients had an increased overall mortality (SMR 1.79, 95%CI 1.39-2.27) and were at higher risk of dying from cancer (SMR 2.57, 95%CI 1.28-5.13) and non-cancer diseases of the respiratory system (SMR 2.51, 95%CI 1.05-6.04), brain cancer (SMR 6.26, 95%CI 1.57-25.02) and non-cancer diseases of the genitourinary system (SMR 4.38, 95%CI 1.10-17.52). CONCLUSIONS: IBD patients should be offered counselling on risk reduction strategies, as much of their mortality excess is potentially avoidable.

Dietary and lifestyle determinants of malondialdehyde DNA adducts in a representative sample of the Florence City population.

Malondialdehyde (MDA), a biomarker of lipid peroxidation and oxidative stress, is a mutagenic and carcinogenic compound that can react with DNA to form several types of DNA adducts including the deoxyguanosine adduct (M1dG). The aim of this cross-sectional study was to evaluate the association between individual dietary and lifestyle habits and M1dG levels, measured in peripheral leukocytes in a large representative sample of the general population of Florence City (Italy). Selected anthropometric measurements, detailed information on dietary and lifestyle habits and blood samples were available for 313 adults of the Florence City Sample enrolled in the frame of European Prospective Investigation into Cancer and nutrition (EPIC) study. A multivariate regression analysis adjusted for selected individual characteristics possibly related to M1dG levels (sex, age, BMI, smoke, physical activity level, education level, total caloric intake and a Mediterranean dietary score) was performed to estimate the association between these parameters and M1dG levels. M1dG levels were significantly higher in women (P = 0.014) and lower in moderately active or active subjects (P = 0.037).We also found a significant inverse association with the Modified Mediterranean dietary score (P for trend = 0.049), particularly evident for the highest categories of adherence. Our results indicate that M1dG levels can be modulated by selected individual characteristics such as gender, physical activity and a Mediterranean dietary pattern.

[Alcohol consumption and epithelial cancer risk in the EPIC-Italy cohort]. / Consumo di bevande alcoliche e rischio di tumori epiteliali nella coorte EPIC-Italia.

OBJECTIVES: to evaluate the association between baseline and lifetime alcohol consumption and the risk of epithelial cancer (all types) in the Italian cohort of the European Prospective Investigation into Cancer and nutrition (EPIC) study. DESIGN: prospective study carried out in a large Italian population. SETTING AND PARTICIPANTS: detailed information on the consumption of alcoholic beverages at baseline and over lifetime collected at enrolment into the EPIC study (1993-1998) by standardised questionnaires for 44,477 healthy adults. MAIN OUTCOMES MEASURES: 2,640 incident epithelial cancers identified during a mean follow-up of 11.4 years. Multivariate Cox proportional hazard models adjusted for several potential confounders were used to calculate hazard ratios (HR) and corresponding 95% confidence intervals (CI). RESULTS: lifetime alcohol consumption (p for trend =0.005) was associated with epithelial cancer risk in the whole cohort. This effect was more evident in women (p =0.049) and in current smokers (p =0.012). Alcohol consumption at baseline was associated with the epithelial cancer risk in women (p for trend =0.01) and current smokers (p for trend =0.02). A significant interaction between alcohol consumption and smoke duration (p =0.015 for baseline; p =0.006 for lifetime) was identified. CONCLUSIONS: in this large Italian population, alcohol consumption, particularly lifetime, is a significant risk factor for the development of epithelial cancers. This effect appears to be modulated by smoking habits.

Surface imaging, portal imaging, and skin marker set-up vs. CBCT for radiotherapy of the thorax and pelvis.

AIM: The aim of this study was to compare surface imaging, portal imaging, and skin marker set-up in radiotherapy of thoracic and pelvic regions, using cone beam computed tomography (CBCT) data as the gold standard. PATIENTS AND METHODS: Twenty patients were included in this study. CBCT, surface acquisition (SA), and two orthogonal portal images (PI) were acquired during the first four treatment sessions. Patient set-up corrections, obtained by registering the planning CT with CBCT, were used as the gold standard. Registration results of the PI and SA were evaluated and compared with those obtained with CBCT. The advantage derived from using SA or PI verification systems over a skin marker set-up was also quantified. RESULTS: A statistically significant difference between PI and SA (in favour of PI) was observed in seven patients undergoing treatment of the pelvic region and in two patients undergoing treatment of the thoracic region. The use of SA or PI, compared with a skin marker set-up, improved patient positioning in 50% and 57% of the thoracic fractions, respectively. For pelvic fractions, the use of PI was beneficial in 73% of the cases, while the use of SA was beneficial in only 45%. Patient positioning worsened with SA, particularly along longitudinal and vertical directions. CONCLUSION: PI yielded more accurate registration results than SA for both pelvic and thoracic fractions. Compared with the skin marker set-up, PI performances were superior to SA for pelvic fractions while comparable results were obtained for thoracic fractions.

Plasma clusterin as a candidate pre-diagnosis marker of colorectal cancer risk in the Florence cohort of the European Prospective Investigation into Cancer and Nutrition: a pilot study.

BACKGROUND: Colorectal cancer is one of the major causes of cancer mortality world-wide. Prevention would improve if at-risk subjects could be identified. The aim of this study was to characterise plasma protein biomarkers associated with the risk of colorectal cancer in samples collected prospectively, before the disease diagnosis. METHODS: After an exploratory study on the comprehensive plasma proteome analysis by liquid chromatography-tandem mass spectrometry from ten colorectal cancer cases enrolled at diagnosis, and ten matched controls (Phase 1), a similar preliminary study was performed on prospective plasma samples from ten colorectal cancer cases, enrolled years before disease development, and ten matched controls identified in a nested case-control study within the Florence cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) study (Phase 2); in Phase 3 the validation of the candidate biomarkers by targeted proteomics on 48 colorectal cancer cases and 48 matched controls from the Florence-EPIC cohort, and the evaluation of the disease risk were performed. RESULTS: Systems biology tools indicated that both in the Phase 1 and Phase 2 studies circulating protein levels differing in cases more than 1.5 times from controls, were involved in inflammation and/or immune response. Eight proteins including apolipoprotein C-II, complement C4-B, complement component C9, clusterin, alpha-2-HS-glycoprotein, mannan-binding lectin serine-protease, mannose-binding protein C, and N-acetylmuramoyl-L-alanine amidase were selected as promising candidate biomarkers. Targeted proteomics of the selected proteins in the EPIC samples showed significantly higher clusterin levels in cases than controls, but only in men (mean ± SD, 1.98 ± 0.46 and 1.61 ± 0.43 nmol/mL respectively, Mann-Whitney U, two-tailed P = 0.0173). The remaining proteins were unchanged. Using multivariate logistic models a significant positive association emerged for clusterin, with an 80% increase in the colorectal cancer risk with protein's unit increase, but only in men. CONCLUSIONS: The results show that plasma proteins can be altered years before colorectal cancer detection. The high circulating clusterin in pre-diagnostic samples suggests this biomarker can improve the identification of people at risk of colorectal cancer and might help in designing preventive interventions.

Omega-6 and omega-3 polyunsaturated fatty acid levels are reduced in whole blood of Italian patients with a recent myocardial infarction: the AGE-IM study.

OBJECTIVE: The relationship between whole blood fatty acids and myocardial infarction (MI) risk has not been analyzed in detail, especially in Mediterranean countries. The AGE-IM (Acidi Grassi Essenziali e Infarto Miocardico) study was planned to examine the relationships between MI, whole blood fatty acids and the diet in an Italian cohort. METHODS: 119 Patients with a recent MI and 103 control subjects were enrolled in the study. The whole blood fatty acid composition was determined; information on anthropometrics, biochemical parameters and blood pressure values were also obtained. Diet composition was assessed using a validated food frequency questionnaire from 86 cases and 72 controls. RESULTS: Total PUFA, omega-6 and omega-3 PUFA (as percentage of whole blood fatty acids) were significantly lower in MI patients than in matched controls, whereas saturated and monounsaturated fatty acids were higher in cases. MI infarction risk significantly and steadily decreased with increasing levels of total PUFA (OR: 0.14) and of total omega-6 and omega-3 (OR: 0.15 and 0.37, respectively). No correlation was identified between dietary fats and MI risk or between whole blood fatty acid levels and dietary nutrients and fats. CONCLUSION: Percentage levels of total PUFA, total omega-3 PUFA and total omega-6 PUFA are lower in MI patients than in matched control subjects in the AGE-IM cohort. These data support a favorable association not only of whole blood percentage levels of total omega-3, but also of total omega-6, with cardiovascular risk.

New frontiers in sport training: genetics and artistic gymnastics.

The increasing understanding of the genetic influences in sport has prompted an association study between the athletic performances and the polymorphisms of the angiotensin-converting enzyme (ACE), the α-actinin-3 (ACTN3), and the vitamin D receptor genes. The details of these gene polymorphisms can provide useful information to improve and plan new modern training programs for elite athletes. Eighty Italian male high level gymnasts were trained and tested for gymnastic-specific exercises and tested in all the men's artistic gymnastic apparatus (floor, pommel horse, rings, vault, parallel bars, and horizontal bar), and then genotyped. The training parameters of volume, intensity, and density of each gymnast were periodically measured during the season in each apparatus from the tests performed, and the seasonal average values were calculated. Gene polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism assay and studied in association with the performance results. The performances of ACE II gymnasts were significantly lower than that of the ACE ID/DD gymnasts in the apparatus expressing power features, confirming the predisposition of these athletes toward power-oriented sport. Gymnasts with ACTN3 RR/RX genotypes did not show a predisposition to the power-oriented apparatus, having worse performances compared with that of the ACTN3 XX gymnasts. Similarly, gymnasts with ACE II + ACTN3 RR/RX combined genotypes showed lower performances in comparison with that of the other gymnasts. Vitamin D receptor polymorphisms showed no significant association with the athletic performances. Because ACE insertion/deletion (I/D) and ACTN3 R577X polymorphisms heavily affect the physical performance of elite male gymnasts, the Italian Gymnastic Federation trainers have started to customize the current high-level training programs.

Atypical and malignant meningioma: outcome and prognostic factors in 68 irradiated patients.

Meningiomas account for up to 20 % of all primary intracranial neoplasms; although the majority of these have a benign course, as many as 5-10 % can display more aggressive behavior and a higher incidence of disease progression. The benefit of immediate adjuvant radiotherapy is still being debated for atypical and malignant meningiomas. This study aimed to retrospectively assess prognostic factors and outcome in 68 patients with atypical and malignant meningiomas. Sixty-eight meningioma patients were treated with radiotherapy after initial resection or for recurrence, between January 1993 and December 2011. Surgery was macroscopically complete in 80 % of the patients; histology was atypical and malignant in 51 patients and 17 patients, respectively. Mean dose of radiotherapy was 54.6 Gy. Fifty-six percent of all patients received radiotherapy after surgical resection, 26 % at the first relapse, and 18 % at the second relapse. Median follow-up was 6.7 years, (range 1.5-19.9 years). The 5- and 10-year actuarial overall survival (OS) rates were 74.1 and 45.6 %, respectively. At univariate analysis age >60 years, radiotherapy dose >52 Gy showed statistical significance, (p = 0.04 and p = 0.03, respectively). At the multivariate analysis radiotherapy dose >52 Gy maintained the statistical significance, (p = 0.037). OS of patients treated with radiotherapy at diagnosis was longer than the survival of patients treated with salvage radiotherapy; however this difference did not reach statistical significance when tested for the entire series or for the subgroups of grade 2 and grade 3 patients. The 5- and 10-year disease-free survival (DFS) rates were 76.5 and 69.5 %, respectively, and were significantly influenced by size >5 cm (p = 0.04) and grading (p = 0.003) on univariate analysis. At multivariate analysis, size and grading both remained significant prognostic factors, p = 0.044 and p = 0.0006, respectively. Grade ≤ 2 acute side effects were seen during radiotherapy treatment in 16 % of the patients, with no ≥ grade 3 acute toxicity, based on the Common Terminology Criteria for Adverse Events. In this mono-institutional retrospective study, age and radiotherapy dose were associated with a longer OS, while preoperative size and grading of the tumor influenced DFS. Although there were some advantages in terms of OS for patients treated with postoperative radiotherapy, the benefit did not reach the significance. Multicenter prospective studies are necessary to clarify the management and the correct timing of radiotherapy in such a rare disease.

A retrospective observational analysis to evaluate the off-label use of bevacizumab alone or with irinotecan in recurrent glioblastoma.

BACKGROUND: Recurrent glioblastoma is nearly always fatal, with median survival rates of approximately 12-14 months. Previous phase II clinical trials showed promising results with bevacizumab, alone or in combination with irinotecan, in patients with recurrent glioblastoma. OBJECTIVE: To assess whether the survival of patients with recurrent glioblastoma receiving bevacizumab alone or with irinotecan in everyday practice is comparable to that reported in clinical trials. SETTING: This was a retrospective observational study conducted at a single hospital in Italy. METHOD: Patients with recurrent glioblastoma who had received bevacizumab alone or with irinotecan from January 2009 to September 2011 were included in our study. MAIN OUTCOME MEASURE: Progression-free survival (PFS) and overall survival (OS), and rates of PFS and OS at 6 months. RESULTS: Median PFS was 5.1 months in the bevacizumab group (n = 9) and 15.4 months in the bevacizumab + irinotecan group (n = 10), with 6-month PFS rates of 45 and 69%, respectively. Median OS was 6.8 months for bevacizumab alone and 11.1 months for bevacizumab + irinotecan, with 6-month OS rates of 100 and 90%, respectively. CONCLUSION: Although the number of patients included is not sufficient to allow a conclusive statement about the place of bevacizumab in the treatment of recurrent glioblastoma, the data appear promising, and are consistent with the results of clinical trials.