Publications

The relation between body mass index and prevalence of 17 chronic diseases or groups of diseases was analysed using data from the 1983 Italian National Health Survey, based on a sample of 72,284 individuals aged 15 or over randomly selected within strata of geographical area, size of place of residence and of household in order to be representative of the whole Italian population. The prevalence of diabetes was directly and strongly related to body weight (age-adjusted relative risk estimates being 1.5 for overweight and 2.7 for obese men compared with normal weight individuals; 1.6 and 2.4 for overweight and obese women). Other conditions directly related to self-reported measures of body weight were hypertension (relative risk = 1.7 for obese men and 1.9 for women), myocardial infarction (relative risk = 1.5 for obese men, 1.6 for women), other heart diseases (relative risk = 1.7 for obese men, 1.5 for women), haemorrhoids or varices (relative risk = 1.2 for obese men, 1.5 for women), cholelithiasis (relative risk = 1.2 for obese men, 1.4 for women), urolithiasis and arthritis. Chronic respiratory disorders showed a U-shaped relation to measures of body weight, since their prevalence was elevated in both under- and over-weight individuals. Anaemias and gastroduodenal ulcer showed an inverse relation to body weight, whereas no association was apparent with allergy, liver cirrhosis, and psychiatric or neurological disorders. Allowance for the two major identified covariates (education and smoking) failed to explain the observed variations between measures of body weight and disease, while separate inspection of various strata of age indicated that for most diseases the elevated risks of obesity were higher in younger and decrease steadily with advancing age. Thus, the results of this national survey indicate that overweight has a widespread and substantial impact not only on mortality but also on morbidity from different chronic conditions.

<p>Supplementary Fig. 1: Patient Flow Diagram. Supplementary Fig. 2: Akkermansia muciniphila positive patients present a prolonged PFS and higher gut microbial diversity. Supplementary Fig. 3: Bioactivity of the CD19/CD28-ζ CAR-T cells in our mouse model. Supplementary Fig. 4: Exploration of TME in B-cell lymphoma patients receiving CD19 CAR-T cells. Supplementary Fig. 5: Comprehensive phenotypic characterization of CAR-T cells infiltrating organs in our immunocompetent mouse model. Supplementary Fig. 6: Characterization of bone marrow composition in B-cell lymphoma patients receiving CD19 CAR-T cells. Supplementary Fig. 7: Akkermansia spp. fails to translocate to distal organs. Supplementary Fig. 8: Tryptophan-derived indoles in mice and patients treated with CAR-T cell therapy. Supplementary Fig. 9: Graphical abstract.</p>

Exposure to airborne polycyclic aromatic hydrocarbons (PAHs) in 65 employees (40 sampled both in summer and winter, 15 sampled in summer only, and 10 sampled in winter only) with no occupational exposure to PAHs was assessed by measuring: personal exposure to pyrene, urinary excretion of 1-hydroxypyrene (1-OHP), and benzo(a)pyrene diol epoxide adducts to hemoglobin (BPDE-Hb). Overall, office employees were exposed to significantly higher levels of pyrene in winter (4.54 +/- 2.35 ng/m3, mean +/- SD) than in summer (1.67 +/- 1.92 ng/m3, mean +/- SD; P < 0.001), but no such seasonal variability was observed in 1-OHP excretion. Tobacco smoking was the major determinant of 1-OHP excretion. BPDE-Hb adducts were measured by gas chromatography-mass spectrometry as benzo(a)pyrene tetrols (BPT) released from adducted hemoglobin. In the 65 employees analyzed, mean BPT levels +/- SD were higher in winter (0.14 +/- 0.38 fmol/mg Hb) than summer (0.031 +/- 0.022 fmol/mg Hb). This difference was not statistically significant, probably because of the small proportion of subjects with detectable adducts (11% in summer and 16% in winter). BPDE-Hb adducts were not significantly associated with sex, age, diet, smoking habits, or with pyrene levels and 1-OHP excretion. This is the first report providing reference BPDE-Hb adduct values for the general population not occupationally exposed to environmental PAHs and shows a tendency to seasonal variability, with higher BPT levels in winter when environmental PAHs are also high.

The attributable fraction is the candidate tool to quantify individual shares of each risk factor on the disease burden in a population, expressing the proportion of cases ascribable to the risk factors. The original formula ignored the presence of other factors (i.e. multiple risk factors and/or confounders), and several adjusting methods for potential confounders have been proposed. However, crude and adjusted attributable fractions do not sum up to their joint attributable fraction (i.e. the number of cases attributable to all risk factors together) and their sum may exceed one. A different approach consists of partitioning the joint attributable fraction into exposure-specific shares leading to sequential and average attributable fractions. We provide an example using Italian case-control data on oral cavity cancer comparing crude, adjusted, sequential, and average attributable fractions for smoking and alcohol and provide an overview of the available software routines for their estimation. For each method, we give interpretation and discuss shortcomings. Crude and adjusted attributable fractions added up over than one, whereas sequential and average methods added up to the joint attributable fraction = 0.8112 (average attributable fractions for smoking and alcohol were 0.4894 and 0.3218, respectively). The attributable fraction is a well-known epidemiological measure that translates risk factors prevalence and disease occurrence in useful figures for a public health perspective. This work endorses their proper use and interpretation.

Hand Grip Strength (HGS) is employed in epidemiological contexts to measure muscle strength because it’s inexpensive, easy to perform and interpret. Population-based investigations use protocols that incorporate HGS measurements in health-status evaluations. Our aim was to investigate the association of HGS with all-cause mortality in a South African population. Methods This study was based on the South African leg of the Prospective Urban and Rural Epidemiology (PURE) study; a community-based, prospective cohort study. This work was based on baseline HGS collected in 2005. Deterministic linkage to the mortality was performed using death status in 2018. The Cox regression was applied to investigate all-cause mortality risk in relation to HGS tertiles. A non-linear dose response analysis has been applied to investigate the shape of the relation between HGS and all-cause mortality risk. All the results have been validated by numerous sensitivity analyses. Results Our work included 1 251 participants with a median age of 47 years (5th95th quantile range 36, 67) and 59.6% (n 746) of participants were women. During a median follow-up of 13.2 years, 374 deaths from all causes occurred. We observed a 25% (HR 0.80; 95% CI 0.61, 1.05) and a 63.9% (HR 0.61; 95% CI 0.44, 0.85) decreased risk of all-cause mortality for the 2nd and 3rd tertiles of dominant hand grip strength compared to the 1st. A similar risk reduction was observed for the nondominant hand. A linear monotone decreasing relation between HGS and all-cause mortality risk was reported. Conclusions HGS is inversely associated with mortality risk and can be used to predict mortality risk in the South African population

Tobacco smoking is a well-documented risk factor for several cancers, but the role of cigarette smoking in the etiology of non-Hodgkin lymphoma (NHL) is inadequately understood. Hepatitis C virus (HCV) has been associated with NHL, but the interaction between HCV and smoking habits has not yet been studied. Between 1999 and 2002, we conducted a case-control study on the association of HCV, smoking habits and NHL in 2 areas of northern and southern Italy. Cases were 225 consecutive patients (median age, 59 years) with a new diagnosis of NHL that were admitted to reference and general hospitals. Controls were 504 patients (median age, 63 years) admitted to the same hospitals as cases, for a wide spectrum of acute, nonneoplastic, nonimmune-, nor tobacco-related conditions. Current, heavy smokers (> or = 20 cigarettes/day) had an odds ratio (OR) of NHL of 2.10 (95% confidence interval, CI: 1.07-4.12) compared to never smokers. The association between smoking and NHL was consistent across strata of sex and age. Compared to never smokers, current smokers of > or = 20 cigarettes/day had ORs of 1.14 (95% CI: 0.37-3.56) for B-cell-low-grade, 2.10 (95% CI: 0.94-4.67) for B-cell-intermediate and high-grade, and 25.84 (95% CI: 1.95-342.17) for T-cell NHL. The effect of tobacco smoking and HCV were independent on the relative risk, leading a 4-fold elevated risk in current smokers HCV positive subjects. Tobacco smoking and hepatitis C virus (HCV) have been associated to non-Hodgkin lymphoma (NHL), but the interaction between HCV and smoking habits has not yet been studied. Our study confirms that tobacco is related to NHL, and reports on the combined effect of tobacco smoking and HCV. Infection acted together according to a multiplicative model, leading to a 4-fold elevated risk in current smokers HCV positive subjects.

The authors considered the incidence of second neoplasms among 1,672 oesophageal cancers diagnosed between 1974 and 2004 in the Cancer Registries of the Swiss Cantons of Vaud and Neuchâtel, and followed-up to 2004. A total of 141 second neoplasms were observed versus 38.5 expected, corresponding to a standardized incidence ratio (SIR) of 3.7 (95% confidence interval: 3.1-4.3). The SIRs were statistically significant for cancers of the oral cavity and pharynx (57.3), larynx (24.3), lung (6.6) and intestines (2.6). The SIRs were higher in subjects diagnosed below age 50 and in the first year after diagnosis. The SIR of upper digestive and respiratory tract neoplasms was higher for oesophageal cancers diagnosed in the upper (87.5) and middle (68.1), as compared with the lower third (19.4). There was no rise of second oral, pharyngeal and laryngeal cancer with advancing age, and their incidence tended indeed to decline from 100/1,000 at age 40-49 to 25/1,000 at age 70-79. There was no tendency to rise with age in the incidence of first oesophageal cancer in subjects who subsequently developed another upper digestive or respiratory tract neoplasm. The excess risks of upper digestive and respiratory tract neoplasms are attributable to increased diagnosis and registration of second neoplasms following a diagnosis of oesophageal cancer, as well as to heavy tobacco and alcohol consumption in oesophageal cancer cases. The absence of rise in incidence with age is also compatible with the existence of a subset of the population of susceptible individuals.