Hepatic steatosis, metabolic dysfunction and risk of mortality: findings from a multinational prospective cohort study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are implicated in the aetiology of non-communicable diseases. Our study aimed to evaluate associations between NAFLD and MetS with overall and cause-specific mortality. METHODS: We used dietary, lifestyle, anthropometric and metabolic biomarker data from a random subsample of 15,784 EPIC cohort participants. NAFLD was assessed using the fatty liver index (FLI) and MetS using the revised definition. Indices for metabolic dysfunction-associated fatty liver disease (MAFLD) were calculated. The individual associations of these indices with overall and cause-specific mortality were assessed using multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs). As a subobjective, risk associations with adaptations of new classifications of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic and alcohol-related liver disease (MetALD) were also assessed. RESULTS: Among the 15,784 sub-cohort participants, a total of 1997 deaths occurred (835 due to cancer, 520 to CVD, 642 to other causes) over a median 15.6 (IQR, 12.3-17.1) years of follow-up. Compared to an FLI < 30, FLI ≥ 60 was associated with increased risks of overall mortality (HR = 1.44, 95%CI = 1.27-1.63), and deaths from cancer (HR = 1.32, 95%CI = 1.09-1.60), CVD (HR = 2.06, 95% CI = 1.61-2.63) or other causes (HR = 1.21, 95%CI = 0.97-1.51). Mortality risk associations were also elevated for individuals with MAFLD compared to those without. Individuals with MetS were at increased risk of all mortality endpoints, except cancer-specific mortality. MASLD and MetALD were associated with higher risk of overall mortality. CONCLUSIONS: Our findings based on a prospective cohort suggest that individuals with hepatic steatosis or metabolic dysfunction have a higher overall and cause-specific mortality risk.

Dietary intake of dicarbonyl compounds and changes in body weight over time in a large cohort of European adults.

Dicarbonyl compounds are highly reactive precursors of advanced glycation end products (AGE), produced endogenously, present in certain foods and formed during food processing. AGE contribute to the development of adverse metabolic outcomes, but health effects of dietary dicarbonyls are largely unexplored. We investigated associations between three dietary dicarbonyl compounds, methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG), and body weight changes in European adults. Dicarbonyl intakes were estimated using food composition database from 263 095 European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home in Relation to Anthropometry participants with two body weight assessments (median follow-up time = 5·4 years). Associations between dicarbonyls and 5-year body-weight changes were estimated using mixed linear regression models. Stratified analyses by sex, age and baseline BMI were performed. Risk of becoming overweight/obese was assessed using multivariable-adjusted logistic regression. MGO intake was associated with 5-year body-weight gain of 0·089 kg (per 1-sd increase, 95 % CI 0·072, 0·107). 3-DG was inversely associated with body-weight change (-0·076 kg, -0·094, -0·058). No significant association was observed for GO (0·018 kg, -0·002, 0·037). In stratified analyses, GO was associated with body-weight gain among women and older participants (above median of 52·4 years). MGO was associated with higher body-weight gain among older participants. 3-DG was inversely associated with body-weight gain among younger and normal-weight participants. MGO was associated with a higher risk of becoming overweight/obese, while inverse associations were observed for 3-DG. No associations were observed for GO with overweight/obesity. Dietary dicarbonyls are inconsistently associated with body weight change among European adults. Further research is needed to clarify the role of these food components in overweight and obesity, their underlying mechanisms and potential public health implications.

[The peer-review process: critical issues and challenges from an online survey]. / Il processo della revisione tra pari: criticità e sfide emerse da una survey online.

BACKGROUND: the peer-review process, which is the foundation of modern scientific production, represents one of its essential elements. However, despite numerous benefits, it presents several critical issues. OBJECTIVES: to collect the opinions of a group of researchers from the epidemiological scientific community on peer-review processes. DESIGN: cross-sectional study using a questionnaire evaluation. SETTING AND PARTICIPANTS: a 29-question survey was administered to 516 healthcare professionals through the SurveyMonkey platform. The questions focused on the individual characteristics of the respondents and their perceived satisfaction with some characteristics of the review process as well as their propensity of changing some aspects of it. In addition, three open-ended questions were included, allowing respondents to provide comments on the role that reviewers and the review process should play. Descriptive statistics were produced in terms of absolute frequencies and percentages for the information collected through the questionnaire. Secondly, a multiple logistic regression analysis was conducted to assess the willingness to change certain aspects of peer review, adjusting for covariates such as age, sex, being the author of at least one scientific work, being a reviewer of at least one scientific work, and belonging to a specific discipline. The results are expressed as odds ratios (ORs) and their 95% confidence intervals (95%CI). Text analysis and representation using word cloud were also used for an open-ended question. MAIN OUTCOMES MEASURES: level of satisfaction regarding some characteristics of the peer-review process. RESULTS: a total of 516 participants completed the questionnaire. Specifically, 87.2% (N. 450) of the participants were the authors of at least one scientific publication, 78.7% were first authors at least once (N. 406), and 71.5% acted as reviewers within the peer-review process (N. 369). The results obtained from the multiple logistic regression models did not highlight any significant differences in terms of propensity to change for age and sex categories, except for a lower propensity of the under 35 age group towards unmasking, defined as the presence of reviewers and editorial boards names on the publish article (OR <35 years vs 45-54 years: 0.51; 95%CI 0.29-0.89) and a higher propensity for post-formatting proposals, defined as the possibility of formatting the article following journal guidelines after the acceptance, among those under 45 (OR <35 years vs 45-54 years: 1.73; 95%CI 0.90-3.31; OR 35-44 years vs 45-54 years: 2.02; 95%CI 1.10-3.72). Finally, approximately 50% of respondents found it appropriate to receive credits for the revision work performed, while approximately 30% found it appropriate to receive a discount on publication fees for the same journal in which they acted as reviewers. CONCLUSIONS: the peer-review process is considered essential, but imperfect, by the professionals who participated in the questionnaire, thus providing a clear picture of the value that peer-review adds rigorously to each scientific work and the need to continue constructive dialogue on this topic within the scientific community.

Assessment of the current knowledge about infective endocarditis prevention among dental hygienists in Italy: A national survey.

OBJECTIVES: To date, there is a lack of data regarding the acceptance of the guidelines for infective endocarditis (IE) prevention among dentists in Italy, and similarly, there are no data on the understanding and compliance of those among dental hygienists (DH). Thus, we tried to assess the ability of DH to recognize and manage categories of patients at high risk of EI, to identify which dental procedures are at increased risk and to assess the level of knowledge of doses and how antibiotic prophylaxis should be administered in specific cases. METHODS: An anonymous questionnaire was prepared and made accessible online by sharing a Google Forms® link; general personal data and educational background information were collected to obtain a profile of the participants. RESULTS: A total of 362 DH answered to our web-based survey, showing a prevalent female percentage (86.7%) and the most represented age group of 30-39 years old (43.1%). Regarding the gender differences, there were not overall statistically significant differences; similarly, we did not find any differences regarding the overall number of wrong questions if considering the different ages of the participant and the year of graduation. Graduates in Northern Italy have mistaken fewer questions than graduates in other geographical areas. CONCLUSION: To the best of our knowledge, this is the largest survey about the knowledge of IE for DH ever performed. Because the overprescription of antibiotics contributes to the development of drug resistance, antibiotic stewardship should be at the forefront of patient care. Our data reflect the need for placing a greater emphasis on IE prophylaxis education in training and during continuing professional development events for DH.

Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer.

BACKGROUND: Fatty acid binding protein 4 (FABP-4) is a lipid-binding adipokine upregulated in obesity, which may facilitate fatty acid supply for tumor growth and promote insulin resistance and inflammation and may thus play a role in colorectal cancer (CRC) development. We aimed to investigate the association between circulating FABP-4 and CRC and to assess potential causality using a Mendelian randomization (MR) approach. METHODS: The association between pre-diagnostic plasma measurements of FABP-4 and CRC risk was investigated in a nested case-control study in 1324 CRC cases and the same number of matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A two-sample Mendelian randomization study was conducted based on three genetic variants (1 cis, 2 trans) associated with circulating FABP-4 identified in a published genome-wide association study (discovery n = 20,436) and data from 58,131 CRC cases and 67,347 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. RESULTS: In conditional logistic regression models adjusted for potential confounders including body size, the estimated relative risk, RR (95% confidence interval, CI) per one standard deviation, SD (8.9 ng/mL) higher FABP-4 concentration was 1.01 (0.92, 1.12) overall, 0.95 (0.80, 1.13) in men and 1.09 (0.95, 1.25) in women. Genetically determined higher FABP-4 was not associated with colorectal cancer risk (RR per FABP-4 SD was 1.10 (0.95, 1.27) overall, 1.03 (0.84, 1.26) in men and 1.21 (0.98, 1.48) in women). However, in a cis-MR approach, a statistically significant association was observed in women (RR 1.56, 1.09, 2.23) but not overall (RR 1.23, 0.97, 1.57) or in men (0.99, 0.71, 1.37). CONCLUSIONS: Taken together, these analyses provide no support for a causal role of circulating FABP-4 in the development of CRC, although the cis-MR provides some evidence for a positive association in women, which may deserve to be investigated further.

Population-based cohort study to assess the gingival lesions in 1319 patients with lichen planus.

AIMS: Oral lichen planus (OLP) is a chronic immune disease. In this paper, we evaluated the overall characters, clinical presentation, and outcome of gingival lesions in OLP Italian patients. METHODS AND RESULTS: A retrospective cohort study was accomplished: a total of 1319 charts were investigated, of whom 922 were female (69.9%): 617 patients (46.8%) manifested white lesions and 702 red ones (53.2%). While most patients had several oral sites of involvement, the gingiva was the unique location in 103 cases. Symptoms were reported in 480 patients (36.4%): 286 patients with erosive OLP, 103 with atrophic form, and 91 with a white form. Long-lasting surveillance showed that only 40 patients (3.03%) had a total clinical signs remission. Regarding OLP medical treatment provided, patients attending less frequently a dental office underwent more often a specific therapy. CONCLUSIONS: To the best of our knowledge, this is the biggest collections of patients with gingival OLP ever described; exclusive gingival lesions are, however, rare and unlikely to undergo a malignant transformation. Moreover, gum lesions seemed to anticipate the appearance of oral lesions and a higher rate of OLP therapy was observed in patients with less frequent dental check-ups and oral hygiene instructions.

Identifying MicroRNAs Suitable for Detection of Breast Cancer: A Systematic Review of Discovery Phases Studies on MicroRNA Expression Profiles.

The analysis of circulating tumor cells and tumor-derived materials, such as circulating tumor DNA, circulating miRNAs (cfmiRNAs), and extracellular vehicles provides crucial information in cancer research. CfmiRNAs, a group of short noncoding regulatory RNAs, have gained attention as diagnostic and prognostic biomarkers. This review focuses on the discovery phases of cfmiRNA studies in breast cancer patients, aiming to identify altered cfmiRNA levels compared to healthy controls. A systematic literature search was conducted, resulting in 16 eligible publications. The studies included a total of 585 breast cancer cases and 496 healthy controls, with diverse sample types and different cfmiRNA assay panels. Several cfmiRNAs, including MIR16, MIR191, MIR484, MIR106a, and MIR193b, showed differential expressions between breast cancer cases and healthy controls. However, the studies had a high risk of bias and lacked standardized protocols. The findings highlight the need for robust study designs, standardized procedures, and larger sample sizes in discovery phase studies. Furthermore, the identified cfmiRNAs can serve as potential candidates for further validation studies in different populations. Improving the design and implementation of cfmiRNA research in liquid biopsies may enhance their clinical diagnostic utility in breast cancer patients.

Education inequalities in cardiovascular and coronary heart disease in Italy and the role of behavioral and biological risk factors.

BACKGROUND AND AIMS: Behavioral and biological risk factors (BBRF) explain part of the variability in socioeconomic differences in health. The present study aimed at evaluating education differences in incidence of cardiovascular disease (CVD) and coronary heart disease (CHD) in Italy and the role of BBRF. METHODS AND RESULTS: All subjects aged 30-74 years (n = 132,686) who participated to the National Health Interview Surveys 2000 and 2005 were included and followed-up for ten years. Exposure to smoking, physical activity, overweight/obesity, diabetes and hypertension at baseline was considered. Education level was used as an indicator of socioeconomic status. The outcomes were incident cases of CVD and CHD. Hazard ratios by education level were estimated, adjusting for sociodemographic covariates and stratifying by sex and geographic area. The contribution of BBRF to education inequalities was estimated by counterfactual mediation analysis, in addition to the assessment of the risk attenuation by comparing the models including BBRF or not. 22,214 participants had a CVD event and 6173 a CHD event. After controlling for sociodemographic factors, the least educated men showed a 21% higher risk of CVD and a 17% higher risk of CHD compared to the most educated (41% and 61% among women). The mediating effect (natural indirect effect) of BBRF between extreme education levels was 52% for CVD and 84% for CHD among men (16% among women for CVD). CONCLUSIONS: More effective strategies aiming at reducing socioeconomic disparities in CVD and CHD are needed, through programs targeting less educated people in combination with community-wide initiatives.

Health status assessment of a population of asylum seekers in Northern Italy.

BACKGROUND: Since 2011 Italy has faced an extraordinary increase in migrants arrivals, mainly from the Mediterranean route, one of the world's most dangerous journeys. The purpose of the present article is to provide a comprehensive picture of the migrants' health status in the "T. Fenoglio" centre, Settimo Torinese (Turin, Italy). METHODS: A retrospective cross-sectional study was conducted using data collected from June 2016 to May 2018 on adult migrants (over 18 years old) from Africa, Middle East and South East Asia (Bangladesh, Cambodia, India, Nepal). Data was collected through the migrants' medical records. Descriptive statistics were performed on socio-demographic variables. The diagnosed diseases were anonymously registered and classified according to the International Classification of Primary Care (ICPC-2). Conditional Inference Trees were used to perform a descriptive analysis of the sample and to detect the covariates with the strongest association with the variables Disease on arrival, Disease after arrival, ICPC on arrival and ICPC after arrival. RESULTS: Analyzed observations were 9 857. 81.8% were men, median age was 23 (Interquartile range: 20.0-27.4). 70.3% of the sample came from Sub-Saharan Africa. 2 365 individuals (24%) arrived at the centre with at least one disease. On arrival, skin (27.71%), respiratory (14.46%), digestive (14.73%) and generic diseases (20.88%) were the most frequent. During the stay respiratory diseases were the most common (25.70%). The highest probability of arriving with a disease occurred in 2018 and during the period September-November 2016, in particular for people from the Horn of Africa. During this period and also in the first half of 2017, skin diseases were the most reported. In seasons with lower prevalence of diseases on arrival the most common disease code was generic for both men and women (usually fever or trauma). CONCLUSIONS: This study provides information on the diverse diseases that affect the asylum seekers population. In our sample, the Horn of Africa was the most troubled area of arrival, with severe conditions frequently reported regarding skin diseases, in particular scabies. 2018 was the most critical year, especially for migrants from the Horn of Africa and Sub-Saharan Africa. During the stay at the camp, the prevalence of respiratory diseases increased. However, skin diseases remained the main issue for people from the Horn of Africa. Overall, the most reported diseases in the sample were dermatological, respiratory, digestive and generic diseases, both on arrival and during the stay. A better understanding of the health status of asylum seekers is an important factor to determine a more efficient reception and integration process and a better allocation of economic resources in the context of migrants' health care.

The broad spectrum of COVID-like patients initially negative at RT-PCR testing: a cohort study.

BACKGROUND: Patients that arrive in the emergency department (ED) with COVID-19-like syndromes testing negative at the first RT-PCR represent a clinical challenge because of the lack of evidence about their management available in the literature. Our first aim was to quantify the proportion of patients testing negative at the first RT-PCR performed in our Emergency Department (ED) that were confirmed as having COVID-19 at the end of hospitalization by clinical judgment or by any subsequent microbiological testing. Secondly, we wanted to identify which variables that were available in the first assessment (ED variables) would have been useful in predicting patients, who at the end of the hospital stay were confirmed as having COVID-19 (false-negative at the first RT-PCR). METHODS: We retrospectively collected data of 115 negative patients from2020, March 1st to 2020, May 15th. Three experts revised patients' charts collecting information on the whole hospital stay and defining patients as COVID-19 or NOT-COVID-19. We compared ED variables in the two groups by univariate analysis and logistic regression. RESULTS: We classified 66 patients as COVID-19 and identified the other 49 as having a differential diagnosis (NOT-COVID), with a concordance between the three experts of 0.77 (95% confidence interval (95%CI) 0.66- 0.73). Only 15% of patients tested positive to a subsequent RT-PCR test, accounting for 25% of the clinically suspected. Having fever (odds ratio (OR) 3.32, (95%CI 0.97-12.31), p = 0.06), showing a typical pattern at the first lung ultrasound (OR 6.09, (95%CI 0.87-54.65), p = 0.08) or computed tomography scan (OR 4.18, (95%CI 1.11-17.86), p = 0.04) were associated with a higher probability of having COVID-19. CONCLUSIONS: In patients admitted to ED with COVID-19 symptoms and negative RT-PCR a comprehensive clinical evaluation integrated with lung ultrasound and computed tomography could help to detect COVID-19 patients with a false negative RT-PCR result.

Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study.

Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by the non-enzymatic reaction between amino acids and reducing sugars, or dicarbonyls as intermediate compounds. Experimental studies suggest that AGEs may promote colorectal cancer, but prospective epidemiologic studies are inconclusive. We conducted a case-control study nested within a large European cohort. Plasma concentrations of three protein-bound AGEs-Nε-(carboxy-methyl)lysine (CML), Nε-(carboxy-ethyl)lysine (CEL) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)-were measured by ultra-performance liquid chromatography-tandem mass spectrometry in baseline samples collected from 1378 incident primary colorectal cancer cases and 1378 matched controls. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression for colorectal cancer risk associated with CML, CEL, MG-H1, total AGEs, and [CEL+MG-H1: CML] and [CEL:MG-H1] ratios. Inverse colorectal cancer risk associations were observed for CML (OR comparing highest to lowest quintile, ORQ5 versus Q1 = 0.40, 95% CI: 0.27-0.59), MG-H1 (ORQ5 versus Q1 = 0.73, 95% CI: 0.53-1.00) and total AGEs (OR Q5 versus Q1 = 0.52, 95% CI: 0.37-0.73), whereas no association was observed for CEL. A higher [CEL+MG-H1: CML] ratio was associated with colorectal cancer risk (ORQ5 versus Q1 = 1.91, 95% CI: 1.31-2.79). The associations observed did not differ by sex, or by tumour anatomical sub-site. Although individual AGEs concentrations appear to be inversely associated with colorectal cancer risk, a higher ratio of methylglyoxal-derived AGEs versus those derived from glyoxal (calculated by [CEL+MG-H1: CML] ratio) showed a strong positive risk association. Further insight on the metabolism of AGEs and their dicarbonyls precursors, and their roles in colorectal cancer development is needed.

Lifestyle correlates of eight breast cancer-related metabolites: a cross-sectional study within the EPIC cohort.

BACKGROUND: Metabolomics is a promising molecular tool for identifying novel etiological pathways leading to cancer. In an earlier prospective study among pre- and postmenopausal women not using exogenous hormones, we observed a higher risk of breast cancer associated with higher blood concentrations of one metabolite (acetylcarnitine) and a lower risk associated with higher blood concentrations of seven others (arginine, asparagine, phosphatidylcholines (PCs) aa C36:3, ae C34:2, ae C36:2, ae C36:3, and ae C38:2). METHODS: To identify determinants of these breast cancer-related metabolites, we conducted a cross-sectional analysis to identify their lifestyle and anthropometric correlates in 2358 women, who were previously included as controls in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition cohort and not using exogenous hormones at blood collection. Associations of each metabolite concentration with 42 variables were assessed using linear regression models in a discovery set of 1572 participants. Significant associations were evaluated in a validation set (n = 786). RESULTS: For the metabolites previously associated with a lower risk of breast cancer, concentrations of PCs ae C34:2, C36:2, C36:3, and C38:2 were negatively associated with adiposity and positively associated with total and saturated fat intakes. PC ae C36:2 was also negatively associated with alcohol consumption and positively associated with two scores reflecting adherence to a healthy lifestyle. Asparagine concentration was negatively associated with adiposity. Arginine and PC aa C36:3 concentrations were not associated to any of the factors examined. For the metabolite previously associated with a higher risk of breast cancer, acetylcarnitine, a positive association with age was observed. CONCLUSIONS: These associations may indicate possible mechanisms underlying associations between lifestyle and anthropometric factors, and risk of breast cancer. Further research is needed to identify potential non-lifestyle correlates of the metabolites investigated.

Macronutrient composition of the diet and long-term changes in weight and waist circumference in the EPIC-Italy cohort.

BACKGROUND AND AIMS: The overall macronutrient composition of diet, rather than just calorie intake, may influence long-term changes of anthropometry. We investigated relationships between dietary macronutrient composition and long-term changes in weight and waist circumference in participants of the EPIC-Italy - the Italian section of the European Prospective Investigation into Cancer and Nutrition - study. METHODS AND RESULTS: A total of 32,119 participants provided anthropometric measures at recruitment and 12 years later (mean). Diet at recruitment was assessed using validated semi-quantitative food frequency questionnaires. Weight and waist changes associated with replacing 10% of energy from one macronutrient with 10% of energy from another macronutrient were assessed by multivariable linear regression. Increased energy from total protein at the expense of any other macronutrient was significantly associated with increased weight and waist circumference. Increased starch at the expense of sugar and total protein was associated with significantly decreased weight and waist circumference; when starch replaced total fat, weight significantly decreased. Increased sugar at the expense of starch and total fat was significantly associated with increased weight and waist circumference; but increase at the expense of total protein was significantly associated with decreased weight and waist circumference. CONCLUSION: Our results suggest that increasing protein at the expense of fat or carbohydrates, and reducing starch by increasing other macronutrients, might be associated with increased weight and waist gain.

Evaluating the Suitability and Potential Efficiency of Cannabis sativa Oil for Patients with Primary Burning Mouth Syndrome: A Prospective, Open-Label, Single-Arm Pilot Study.

OBJECTIVE: To evaluate the use of a Cannabis sativa oil in the management of patients diagnosed with primary burning mouth syndrome (BMS). DESIGN: Prospective, open-label, single-arm pilot study. SETTING: University hospital. SUBJECTS: Seventeen patients with diagnosed BMS were included. METHODS: Subjects were treated for 4 weeks with a full cannabis plant extract, which was prepared from standardized plant material (cannabis flos) in specialized pharmacies by means of Romano-Hazekamp extraction and was diluted in oil (1 g of cannabis in 10 g of olive oil). The primary outcome was the change in pain intensity (assessed by the visual analog scale, Present Pain Intensity scale, McGill Pain Questionnaire, and Oral Health Impact Profiles) at the end of the protocol and during the succeeding 24 weeks; the neuropathic pain was also investigated with a specific interview questionnaire (DN4-interview [Douleur Neuropathique en 4 Questions]). Levels of anxiety and depression were considered as secondary outcomes, together with reported adverse events due to the specified treatment. RESULTS: Subjects showed a statistically significant improvement over time in terms of a clinical remission of the oral symptoms. Levels of anxiety and depression also changed statistically, displaying a favorable improvement. No serious reactions were detailed. None of the patients had to stop the treatment due to adverse events. CONCLUSIONS: In this pilot evaluation, the C. sativa oil provided was effective and well tolerated in patients with primary BMS. Further bigger and properly defined randomized controlled trials, with different therapeutic approaches or placebo control, are needed, however.

Characteristics of patients affecting the duration of positivity at SARS-CoV-2: a cohort analysis of the first wave of epidemic in Italy.

OBJECTIVES: to investigate the characteristics of patients affecting the duration of positivity test by RT-PCR in the population of Piedmont, a Region of North-West of Italy. DESIGN: observational cohort study. SETTING AND PARTICIPANTS: from the administrative database of the regional SARS-CoV-2 surveillance system, a cohort of all patients who tested positive by a RT-PCR assay to SARS-CoV-2 occurring from 22.02.2020 to 30.09.2020 in the Piedmont Region (N. 29,292) was obtained. The cohort has been linked to the hospital discharge database and to the vital statistics database. MAIN OUTCOMES MEASURES: outcome of the study was the risk of non negativization, estimated by fitting Generalizing Estimating Equation model (GEE), a longitudinal model which consider for each subject several records collected on fixed time intervals 15, 30, 45 or 60+ days from the first positive test. Negativization was defined as the condition in which two consecutive samples taken from the patient at least 24 hours apart were negative for the presence of SARS-CoV-2. RESULTS: the median duration of positive RT-PCR was 27 days. A higher median of days until positive persistence was observed in people over 80 (34 days, IQR 25-49), female (28 days, IQR 18-40), symptomatic patients (28 days, IQR 19-40), hospitalized people (32 days, IQR 21-44), patients with Charlson's index >0 (34 days, IQR 23-49), patients host of elderly nursing homes (37 days, IQR 25-51). In the GEE multivariable model, the variables associated to the non negativization at all times intervals were: older age (at 15th day: class 65+, OR 2.56, 95%CI 2.39-2.74), female gender (at 15th day: OR 1.12, 95%CI 1.06-1.18), and to be hospitalized for COVID-19 (at 15th day: OR 1.38, 95%CI 1.29-1.48). The presence of comorbidities and of symptoms were associate with the non negativization at 15th day (respectively, class 4+: OR 1.29, 95%CI 1.08-1.56 and symptoms: OR 1.20, 95%CI 1.13-1.27), but not at 45th day. CONCLUSIONS: older age, female gender, presence of comorbidities and severity of disease (proxy hospitalization for COVID-19) were risk factors for non negativization at all times intervals. The presence of symptoms was a risk factors for the non negativization after 2 weeks from the first diagnosis and not at 45th day. Using a longitudinal model for the analysis of the dataset, it is possible to compare the weight of the variables included in the model at different times and correct an overestimation of the attributable risk after the first considered time interval.

Urinary flavanone concentrations as biomarkers of dietary flavanone intakes in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

In the present study, the aim was to investigate the correlation between the acute and habitual dietary intake of flavanones, their main food sources and the concentrations of aglycones naringenin and hesperetin in 24 h urine in a European population. A 24-h dietary recall (24-HDR) and a 24-h urine sample were collected the same day from a subsample of 475 people from four different countries of the European Prospective Investigation into Cancer and Nutrition study. Acute and habitual dietary data were captured through a standardised 24-HDR and a country/centre-specific validated dietary questionnaire (DQ). The intake of dietary flavanones was estimated using the Phenol-Explorer database. Urinary flavanones (naringenin and hesperetin) were analysed using tandem MS with a previous enzymatic hydrolysis. Weak partial correlation coefficients were found between urinary flavanone concentrations and both acute and habitual dietary flavanone intakes (Rpartial = 0·14-0·17). Partial correlations were stronger between urinary excretions and acute intakes of citrus fruit and juices (Rpartial ∼ 0·6) than with habitual intakes of citrus fruit and juices (Rpartial ∼ 0·24). In conclusion, according to our results, urinary excretion of flavanones can be considered a good biomarker of acute citrus intake. However, low associations between habitual flavanone intake and urinary excretion suggest a possible inaccurate estimation of their intake or a too sporadic intake. For assessing habitual exposures, multiple urinary collections may be needed. These results show that none of the approaches tested is ideal, and the use of both DQ and biomarkers can be recommended.

Short-term effect of colorectal cancer on income: analysis of an Italian cohort.

INTRODUCTION: The ability to return to work after a cancer diagnosis is a key aspect of cancer survivorship and quality of life. Studies have reported a significant risk of income loss for cancer survivors; however, there is limited evidence of the Italian context. METHODS: The Work Histories Italian Panel (WHIP)-Salute database was used to select a cohort of incident cases of colorectal cancer (CRC) among workers in the private sector, based on hospital discharges. A propensity score matching was used to find a balanced control group for several confounders. Ordinary least square and logistic regressions were used to estimate the effect of a CRC diagnosis on annual income and the probability of switching from a full-time contract to a part-time one considering 3 years after the diagnosis. RESULTS: Overall, we identified 925 CRC incident cases from 2006 until 2012. Our results confirm a statistically significant reduction in survivors' income compared with controls. This reduction was greater in the first year and then tend to decrease, with an average income loss over 3 years of about €12 000. Stratified analyses by sex and position confirmed the overall trend while indicating a strong effect modification. Regarding the switching from full-time to part-time employment, the results were never significant. CONCLUSION: Income loss does not seem to be related to an increase in part-time contracts, but rather to survivors' reduced work capacity following the invasive treatments. Further research is needed to investigate the complex dynamics behind this association.

[A national overview of the topics covered by young people in epidemiology: a comparison before and after the Covid-19.] / Un quadro nazionale delle tematiche trattate dai giovani in epidemiologia: un confronto prima e dopo il Covid-19.

INTRODUCTION: Epidemiology is increasingly involved on a wide variety of topics and to engage different professionals and disciplines in an increasingly active way. A fundamental role is played by young researchers active in Italian epidemiology who create opportunities for meeting and discussion, in the name of multidisciplinarity and integration of different skills. OBJECTIVE: The aim of this paper is to provide a detailed description of the topics most frequently studied in epidemiology by young people and to highlight any changes in these topics in the pre- and post-Covid-19 workplaces. METHODS: All abstracts submitted in the years 2019 and 2022 by young participants in the Maccacaro Prize, an annual award aimed at Italian association of epidemiology (Aie) conference addressed to people under 35 years of age, were considered. In addition to the comparison of the topics, a comparison of the related work structures and their geographical location was carried out by grouping the research centres into three Italian geographical regions: north, centre and south/islands. RESULTS: Between 2019 and 2022, the number of abstracts participating in the Maccacaro Prize increased. The interest in topics related to infectious diseases, vaccines, and pharmaco-epidemiology has sharply increased, while in environmental and maternal and child epidemiology it has moderately increased. Social epidemiology, health promotion and prevention, as well as clinical and evaluative epidemiology, have experienced a decrease in interest. Finally, after analysing the geographical distribution of reference centres, it was discovered that certain regions, such as Piedmont, Lombardy, Veneto, Emilia-Romagna, Tuscany and Latium, have a strong and consistent presence of young people in the field of epidemiology. Conversely, there is a small number of young professionals working in this field in other Italian regions, especially in Southern regions. CONCLUSIONS: The pandemic has changed our personal and working habits, but it has also played a fundamental role in making epidemiology known. The increase in young people joining an association such as the Aie is a clear sign of the growing interest in this discipline.

Multimorbidity and SARS-CoV-2-Related Outcomes: Analysis of a Cohort of Italian Patients.

BACKGROUND: Since the outbreak of the COVID-19 pandemic, identifying the main risk factors has been imperative to properly manage the public health challenges that the pandemic exposes, such as organizing effective vaccination campaigns. In addition to gender and age, multimorbidity seems to be 1 of the predisposing factors coming out of many studies investigating the possible causes of increased susceptibility to SARS-CoV-2 infection and adverse outcomes. However, only a few studies conducted have used large samples. OBJECTIVE: The objective is to evaluate the association between multimorbidity, the probability to be tested, susceptibility, and the severity of SARS-CoV-2 infection in the Piedmont population (Northern Italy, about 4 million inhabitants). For this purpose, we considered 5 main outcomes: access to the swab, positivity to SARS-CoV-2, hospitalization, intensive care unit (ICU) admission, and death within 30 days from the first positive swab. METHODS: Data were obtained from different Piedmont health administrative databases. Subjects aged from 45 to 74 years and infections diagnosed from February to May 2020 were considered. Multimorbidity was defined both with the Charlson Comorbidity Index (CCI) and by identifying patients with previous comorbidities, such as diabetes and oncological, cardiovascular, and respiratory diseases. Multivariable logistic regression models (adjusted for age and month of infection and stratified by gender) were performed for each outcome. Analyses were also conducted by separating 2 age groups (45-59 and 60-74 years). RESULTS: Of 1,918,549 subjects, 85,348 (4.4%) performed at least 1 swab, of whom 12,793 (14.9%) tested positive for SARS-CoV-2. Of these 12,793 subjects, 4644 (36.3%) were hospitalized, 1508 (11.8%) were admitted to the ICU, and 749 (5.9%) died within 30 days from the first positive swab. Individuals with a higher CCI had a higher probability of being swabbed but a lower probability of testing positive. We observed the same results when analyzing subjects with previous oncological and cardiovascular diseases. Moreover, especially in the youngest group, we identified a greater risk of being hospitalized and dying. Among comorbidities considered in the study, respiratory diseases seemed to be the most likely to increase the risk of having a positive swab and worse disease outcomes. CONCLUSIONS: Our study shows that patients with multimorbidity, although swabbed more frequently, are less likely to get infected with SARS-CoV-2, probably due to greater attention on protective methods. Moreover, a history of respiratory diseases is a risk factor for a worse prognosis of COVID-19. Nonetheless, whatever comorbidities affect the patients, a strong dose-response effect was observed between an increased CCI score and COVID-19 hospitalization, ICU admission, and death. These results are important in terms of public health because they help in identifying a group of subjects who are more prone to worse SARS-CoV-2 outcomes. This information is important for promoting targeted prevention and developing policies for the prioritization of public health interventions.

Exploratory Genome-Wide Association Analysis to Identify Pharmacogenetic Determinants of Response to R-CHOP in Diffuse Large B-Cell Lymphoma.

R-CHOP standard chemotherapy is successful in about 60% of diffuse large B-cell lymphoma (DLBCL) patients. Unresponsive patients have a poor prognosis, and predictive biomarkers of response to R-CHOP are lacking. We conducted the first prospective GWAS study aimed at exploring constitutional biomarkers predictive of R-CHOP efficacy and toxicity. Overall, 216 any-stage chemonaïve DLBCL patients candidate to R-CHOP were enrolled. The median age of the 185 eligible patients was 59.2 years, 49.7% were women and 45.4% were stage I-II patients. According to the Revised International Prognostic Index (R-IPI), 14.1%, 56.8% and 29.2% were in the very good, good and poor prognosis groups, respectively. Of the patients, 85.9% produced a complete response. Highly significant associations (i.e., p < 5 × 10-8) were found between progression-free survival (PFS) and six SNPs (i.e., rs116665727, rs1607795, rs75614943, rs77241831, rs117500207, rs78466241). Additionally, five SNPs (i.e., rs74832512, rs117500207, rs35789195, rs11721010, rs12356569) were highly associated with overall survival (OS). Wild-type patients showed a prolonged PFS or OS compared with patients carrying deleterious alleles (p < 0.001). No association with the adequate significant threshold was observed between SNPs and the objective response or toxicity. In the future, these SNPs, alone or in combination, after a proper validation in an independent cohort, could contribute to improving the prediction of R-CHOP response.