Publications

Abstract Suicide is a serious but preventable public health issue globally, with substantial geographical disparities. Although mortality from suicide is higher in older age groups, it ranks as the fourth leading cause of death among youth. This study analysed global suicide trends for the age group 10-24, from 1990 to 2020. Using data on certified deaths from suicide (codes ICD-9: E950-959; ICD-10: X60-X84, Y87.0) and population from the WHO mortality database for 52 countries with valid data, age-standardised suicide rates (ASR) were computed (by sex, country, and calendar year) and joinpoint regression analyses were carried out to identify significant changes in trends. High variability in suicide rates and trends was observed, with male-to-female ratios ranging from two to five. From 1990 to 2020, most European countries reported declining suicide trends, with some exceptions. Particularly concerning trends emerged in the United Kingdom, with increases of 2.5% per year among males since 2005 and 8.5% among females since 2012. Southern Europe exhibited the most favourable trends and lowest suicide rates, with 3.1/100,000 males in Italy (2020) and 3.5/100,000 males in Spain (2021), and 0.9/100,000 females in Italy (2020) and 1.1/100,000 females in Romania (2019) among females. Conversely, Central-Eastern Europe showed the highest rates, with 10.2/100,000 males in the Russian Federation (2019) and 10.0/100,000 males in Poland (2002). Non-European areas reported higher suicide rates and significant increases. The highest ASR was 15.5/100,000 males in the United States of America, with an increase of 3.8% per year among males from 2009 to 2020 and 6.7% among females from 2007 to 2017, followed by a levelling off. Youth suicide rates and trends vary widely globally. Interpretation of temporal and geographical comparisons in suicide mortality should be approached cautiously due to potential misclassification or under-reporting of suicide deaths in some countries. Key messages • Albeit data on suicide mortality should be interpreted with caution, the study reveals high variability in suicide rates and trends among youths aged 10-24 across different countries worldwide. • Timely and accurate monitoring of epidemiological trends should support the planning, implementation, and evaluation of setting-specific health promotion strategies in mental health.

<div>Abstract<p>This study investigates the clinical relevance of the gut microbiome at taxonomic and metabolic levels in anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, both in patients and in a preclinical syngeneic tumor model. Patients with B-cell lymphoma treated with CD19 CAR T cells exhibited profound intestinal dysbiosis, exacerbated after CAR T-cell infusion. This dysbiosis was characterized by low bacterial richness, low soluble MAdCAM-1, and loss of <i>Akkermansia</i> species, associated with resistance to therapy. Mechanistically, oral <i>Akkermansia massiliensis</i> supplementation increased CAR T-cell infiltration into the bone marrow, inverted the CD4/CD8 CAR T-cell ratio, favored Tc1 CD8<sup>+</sup> T-cell polarization, and promoted the release of tryptophan-derived indole metabolites, leading to better tumor control. The clinical benefit of <i>Akkermansia</i> spp. supplementation was abolished when CAR T cells were genetically deficient in the indole receptor, aryl hydrocarbon receptor (AhR). AhR-agonistic indoles alone failed to replicate the bacterium’s anticancer effects. These findings suggest that <i>Akkermansia</i> supplementation could improve CAR T-cell potency in patients with intestinal <i>Akkermansia</i> deficiency.</p>Significance:<p>B-cell lymphoma patients treated with CAR T cells harbor major gut microbiota perturbations and related metabolism that restrain CAR T-cell therapy. Reprogramming the gut microbiota ecosystem by oral <i>A. massiliensis</i> supplementation induces CAR T-cell niching and Tc1 differentiation in the bone marrow, promoting tumor control in an <i>AhR-</i>dependent manner.</p></div>

Prebiotics may influence the risk of hormone-related female cancers by modulating the gut microbiota involved in estrogen metabolism. We evaluated the association of fiber-type prebiotic intake with breast, endometrial, and ovarian cancers. Data derived from a network of Italian hospital-based case-control studies (1991-2006), including 2560 cases of cancer of the breast (n = 2588 control participants), 454 of the endometrium (n = 908 control participants), and 1031 of the ovary (n = 2411 control participants). Inulin-type fructans and selected fructo-oligosaccharides (namely, nystose, kestose, and 1F-β-fructofuranosylnystose) and galacto-oligosaccharides (namely, raffinose and stachyose) were quantified in food products via laboratory analyses. Prebiotic intake was estimated by multiplying intake according to food frequency questionnaire responses by the foods' prebiotic content. Odds ratios (ORs) and the corresponding 95% CIs were derived by multiple logistic regression models. Nystose intake was marginally directly associated with breast (for quartile 4 vs quartile 1: OR = 1.20; 95% CI, 1.00-1.45), ovarian (OR = 1.39; 95% CI, 1.04-1.84), and endometrial (OR = 1.32; 95% CI, 0.85-2.03) cancer risk. High amounts of 1F-β-fructofuranosylnystose intake were inversely associated with ovarian cancer (OR = 0.67; 95% CI, 0.52-0.85). Inulin-type fructans, kestose, raffinose, and stachyose were not associated with the 3 cancers. The intake of most fiber-type prebiotics was not appreciably and consistently associated with breast, endometrial, and ovarian cancer risks. This article is part of a Special Collection on Gynecological Cancer.

About a quarter of cancer deaths in 2019 in Italy may be prevented by reducing the socioeconomic determinants that contribute to educational disparities in cancer mortality.

Dietary folate intake has been identified as a potentially modifiable factor of gastric cancer (GC) risk, although the evidence is still inconsistent. We evaluate the association between dietary folate intake and the risk of GC as well as the potential modification effect of alcohol consumption. We pooled data for 2829 histologically confirmed GC cases and 8141 controls from 11 case-control studies from the international Stomach Cancer Pooling Consortium. Dietary folate intake was estimated using food frequency questionnaires. We used linear mixed models with random intercepts for each study to calculate adjusted odds ratios (OR) and 95% confidence interval (CI). Higher folate intake was associated with a lower risk of GC, although this association was not observed among participants who consumed >2.0 alcoholic drinks/day. The OR for the highest quartile of folate intake, compared with the lowest quartile, was 0.78 (95% CI, 0.67-0.90, P-trend = 0.0002). The OR per each quartile increment was 0.92 (95% CI, 0.87-0.96) and, per every 100 μg/day of folate intake, was 0.89 (95% CI, 0.84-0.95). There was a significant interaction between folate intake and alcohol consumption (P-interaction = 0.02). The lower risk of GC associated with higher folate intake was not observed in participants who consumed >2.0 drinks per day, OR_{Q4v Q1} = 1.15 (95% CI, 0.85-1.56), and the OR_{100 μg/day} = 1.02 (95% CI, 0.92-1.15). Our study supports a beneficial effect of folate intake on GC risk, although the consumption of >2.0 alcoholic drinks/day counteracts this beneficial effect.

Abstract Cyclic fasting–mimicking diet (FMD) is an experimental nutritional intervention with potent antitumor activity in preclinical models of solid malignancies. FMD cycles are also safe and active metabolically and immunologically in cancer patients. Here, we reported on the outcome of FMD cycles in two patients with chronic lymphocytic leukemia (CLL) and investigated the effects of fasting and FMD cycles in preclinical CLL models. Fasting-mimicking conditions in murine CLL models had mild cytotoxic effects, which resulted in apoptosis activation mediated in part by lowered insulin and IGF1 concentrations. In CLL cells, fasting conditions promoted an increase in proteasome activity that served as a starvation escape pathway. Pharmacologic inhibition of this escape mechanism with the proteasome inhibitor bortezomib resulted in a strong enhancement of the proapoptotic effects of starvation conditions in vitro. In mouse CLL models, combining cyclic fasting/FMD with bortezomib and rituximab, an anti-CD20 antibody, delayed CLL progression and resulted in significant prolongation of mouse survival. Overall, the effect of proteasome inhibition in combination with FMD cycles in promoting CLL death supports the targeting of starvation escape pathways as an effective treatment strategy that should be tested in clinical trials. Significance: Chronic lymphocytic leukemia cells resist fasting-mimicking diet by inducing proteasome activation to escape starvation, which can be targeted using proteasome inhibition by bortezomib treatment to impede leukemia progression and prolong survival.

These findings suggest that diets rich in animal products and animal fats are directly related, and those rich in fruit and vegetables inversely related, to laryngeal cancer risk.

The prediction of numbers and trends for cancer mortality is useful for evaluating disease burden worldwide and reflects the impact of incidence, screening and advancement in early diagnosis and treatments for major cancer sites. Following our recent publication on the estimation of the number of cancer deaths and the corresponding mortality rates for all cancers and selected major cancer sites for the year 2024 in the European Union and the UK [1], here we provide corresponding figures for Italy.

Since the investigation, at an individual level, of lifetime sun exposure remains difficult the site distribution of different types of skin cancer can be an important source of aetiological clues. The present report deals with 1,149 cases of cutaneous malignant melanoma (CMM), 7,685 of basal-cell carcinoma (BCC) and 3,049 of squamous-cell carcinoma (SCC) reported between 1976 and 1992 to the Vaud Cancer Registry, in Switzerland. Site- and type-specific age-standardized (on the world population) incidence rates per 100,000 population and per 100,000 unit surface were computed, together with relative age-standardized incidence rates (i.e., rates per 100,000 surface unit in each anatomical site relative to rates for the body as a whole). The highest rates per unit surface were seen for both genders in the face, thus indicating same role of cumulative sun exposure in all skin-cancer types. Relative to the incidence in the whole body, the excess on the face was, however, more than 20-fold for BCC and SCC, but only 4-fold for CMM. The relative incidence in males was very much higher for SCC than for CMM and BCC in the neck, ears and scalp, a heavily sun-exposed area in men but not in women. Conversely, a substantial lack of SCC was seen in the trunk. In conclusion, site distribution of different skin-cancer types suggests that short-duration UV-light exposure is sufficient to increase CMM risk substantially, but has little influence on SCC risk. With the increase of exposure, however, SCC rises more steeply than BCC. Age-related behaviour (i.e., another indirect indicator of duration of exposure to UV light) is consistent with the anatomical distribution of skin cancer.