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Background Evidence showed the role of biomarkers in predicting severity and mortality of coronavirus disease 2019 (COVID-19). We evaluated associations between several biomarkers measured throughout the follow-up and COVID-19 mortality using the joint modelling (JM) approach, the candidate tool for this kind of data. Methods Between February and May 2020, a total of 403 COVID-19 patients were admitted. Baseline characteristics included sex and age, whereas biomarkers included lymphocytes, neutrophils, D-dimer, ferritin, C-reactive protein, glucose and lactate dehydrogenase (LDH). Hazard ratios (HR) and 95% confidence interval (CI) were estimated through JM using a Bayesian approach. We fitted univariable and multivariable JMs including a single biomarker and the set of all biomarkers, respectively. Results In univariable JMs, all biomarkers were significantly associated with COVID-19 mortality. In the multivariable JM, HRs were 1.78 (95% CI: 1.13–2.87) per doubling of neutrophils levels, 1.49 (95% CI: 1.19–1.95) per doubling of C-reactive protein levels, 2.66 (95% CI: 1.45–4.95) per an increase of 100 mg/dL of glucose, and 1.31 (95% CI: 1.12–1.55) per an increase of 100 U/L of LDH. No evidence of association was observed for ferritin and lymphocytes in the multivariable JM. Men had a higher risk of COVID-19 mortality than women (HR = 1.75; 95% CI: 1.07–2.80) and age showed the strongest effect with risk starting to rapidly increase from 60 years. Conclusions These findings using JM confirm the usefulness of biomarkers in assessing COVID-19 severity and mortality. Monitoring trend patterns of such biomarkers can provide additional help in tailoring the more appropriate care pathway.

Introduction The aim of our study is to describe the management of a maternity ward in a referral center during the COVID-19 pandemic and 2020 lockdown. Methods This is a retrospective single-center study. We analyzed the records of all women consecutively admitted to our delivery ward during lockdown and compared them with those of women admitted in the same period in 2019. Results The number of patients (1260) admitted to our department in 2020 was similar (1215) to that in 2019. Among patients admitted during lockdown, 50 presented with a Sars-CoV-2 infection (3.9%). In 2020, the number of antenatal check-ups was lower than in 2019 [7.9 (1.5) vs 8.2 (1.3), p

The aim of the study was to evaluate the association between SARS-CoV-2 infection and serum hepatic biomarker levels among women with obstetric cholestasis.In this prospective study, we recruited all pregnant women admitted in our hospital with obstetric cholestasis. Among those with a concurrent SARS-CoV-2 infection, we evaluated the following serum hepatic biomarkers: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and biliar acids (BA).Among the 88 women enrolled in the study, 20 presented with a SARS-CoV-2 infection while 68 were negative. SARS-CoV-2 infected women were younger (mean age 30.5 ± 5.7 vs. 34.3 ± 5.4; p 0.01) and in a greater percentage of non-Caucasian ethnicity when compared to noninfected women (60.0% vs. 17.6%; p 0.01). Regarding levels of hepatic biomarkers, they showed higher levels of AST (111.5 ± 134.1 vs. 37.3 ± 43.4 UI/L; p = 0.02), ALT (132.2 ± 115.7 vs. 50.5 ± 73.173.1 UI/L; p 0.01), and BA (41.4 ± 46.8 vs. 18.4 ± 13.4 μmol/L; p = 0.04) compared to noninfected patients. No significant differences in maternal or fetal outcomes were found between infected and noninfected women.SARS-CoV-2 infection was associated with higher levels of liver enzymes in patients with obstetric cholestasis. This could be the result of a possible hepatic involvement in patients with SARS-CoV-2 infection.

Introduction We investigated association between sociodemographic characteristics and COVID‐19 disease among pregnant women admitted to our unit, the largest high‐risk maternity unit in the Milan metropolitan area. Methods Between March 1, 2020 and April 30, 2020, 896 pregnant women were admitted to our Institution and tested for COVID‐19. We collected information regarding their sociodemographic characteristics. Additional information on geographical area of residence, number of family members, number of family members tested positive for COVID‐19, and clinical data was collected for women tested positive for COVID‐19. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of developing COVID‐19 according to sociodemographic characteristics were estimated by unconditional logistic regression models. Results Among the 896 women enrolled, 50 resulted positive for COVID‐19. Pregnant women aged ≥35 years had a significantly lower risk of developing the infection (crude OR = 0.29; 95% CI:0.16–0.55). Conversely, foreign women (crude OR = 3.32; 95% CI:1.89–5.81), unemployed women (crude OR = 3.09; 95% CI: 1.77–5.40), and women with an unemployed partner (crude OR = 3.16; 95% CI: 1.48–6.79) showed a significantly higher risk of infection. Ethnicity was positively associated with the risk of developing COVID‐19 (mutually adjusted OR = 2.15; 95% CI:1.12–4.11) in the multivariate analysis. Foreign women with COVID‐19 were more likely to have a lower education level (p

Evidence suggests a role of serum cholesterol in prostate cancer (PCa) development and of lipid lowering medications in PCa risk reduction. We developed a score for adherence to an established cholesterol-lowering diet and evaluated its association with PCa risk in a multicentric hospital-based case-control study (1294 cases; 1451 matched controls) in Italy (1992-2001). The score was derived from seven dietary indicators which have been reported to lower cholesterol levels: high intake of non-cellulosic polysaccharides (viscous fibres), monounsaturated fatty acids, legumes, seeds/corn oil; low intake of saturated fatty acids, dietary cholesterol, and glycaemic index. Odds ratios (ORs) and corresponding confidence intervals (CIs) were calculated through the unconditional logistic regression model. Although most of the dietary indicators alone were not significantly associated with reduced PCa risk, men who fulfilled 5 to 7 dietary indicators (187 cases and 281 controls) showed a 43% reduction in PCa risk compared to those with 0 to 2 indicators (OR: 0.57; 95% CI: 0.43-0.77). This association was not modified by socio-demographic characteristics or lifestyle factors. In conclusion, adherence to a cholesterol-lowering diet is a favourable factor against the risk of PCa, providing support to dietary guidelines that promote cholesterol reduction through plant-based diets.

OBJECTIVE: In this study we describe the management of women with gestational diabetes (GD) and an ongoing Sars-Cov-2 infection. The aim of the study is to evaluate whether the COVID-19 infection can further complicate pregnancies and thus if the protocol we usually use for GDM pregnancies is also applicable to patients who have contracted a Sars-Cov-2 infection. METHODS: This is a retrospective study analysing all pregnant women with gestational diabetes and a concomitant COVID-19 infection admitted to our Institution for antenatal care between March 1st and April 30th 2020. RESULTS: Among pregnant women with GD and a concomitant COVID-19 infection, the mean age was 32,9 (SD 5,6) years. Two patients (33%) were of Caucasian ethnicity while four (67%) were non-Caucasian. All patients were diagnosed with COVID-19 during the third trimester of pregnancy. Two women were asymptomatic while four were symptomatic. Only two patients (33,3%) received treatment with insulin. None of the patients required intensive care or mechanical ventilation. No complications were found among the newborns. CONCLUSION: the COVID-19 infection was not found to worsen the prognosis of GD patients or of their offspring. Glycaemic monitoring, diet therapy and insulin, when needed, are sufficient for a good metabolic control and a favourable maternal and fetal outcome.

INTRODUCTION The objective of the present study is to compare the sonographic measurement of subcutaneous adipose thickness and visceral adipose thickness during 1st trimester screening for aneuploidies between non-diabetic pregnant women and patients who develop 1st trimester or 2nd trimester gestational diabetes mellitus (GDM). MATERIAL AND METHODS Adipose thickness was measured by transabdominal ultrasound imaging in pregnant women attending our clinic for screening for fetal aneuploidies between 11 and 13 weeks of gestation. During the 1st trimester all patients were evaluated for fasting glycemia in accordance with the International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations. Patients with confirmed fasting glycemia (FPG) ≥92 mg/dL were diagnosed as 1st trimester GDM. Patients with FPG

Introduction: The aim of the present study was to evaluate fetal umbilical artery (UA) and middle cerebral artery (MCA) blood flow in patients with gestational diabetes (GD), in order to determine whether minimal anomalies of glucose metabolism may influence fetal placental function. Methods: UA and MCA flows were prospectively measured by transabdominal ultrasound in singleton pregnancies between 34 and 37 weeks of gestation. Results: The study included 35 women with GD and 217 nondiabetic patients. Middle cerebral pulsatility index (PI) was significantly higher in the GD group (mean MCA-PI = 1.82 ± 0.27 vs. 1.71 ± 0.26; p < 0.02). Likewise, MCA peak systolic velocity (MCA-PSV) was higher in the GD group compared to the non-GD group, though the difference was not significant (mean of MCA-PSV = 47.14 ± 8.45 vs. 47.09 ± 11.21; p = 0.98). UA-PI resulted higher in the non-GD group without significant differences (mean of UA-PI = 0.88 ± 0.14 vs. 0.86 ± 0.15; p = 0.32). Conclusions: Our study shows that even in cases of minimal metabolic derangements, GD is characterized by a significant variation in fetal Doppler velocimetry, particularly in the brain.

Background: The purpose of this study was to describe the placental lesions in pregnancies complicated by hypertensive disorders (HDP) and/or fetal growth restriction (FGR) and in uneventful control pregnancies. Methods: This is a case control study that included singleton pregnancies with HDP and normally grown fetus (HDP-AGA fetus), with HDP and FGR, early FGR, late FGR, and uneventful pregnancies. Feto-placental Doppler velocimetry and sFlt-1/PlGF ratio were performed. Placental histology was evaluated blinded according to the Amsterdam Consensus criteria. Results: Placental lesions with maternal vascular malperfusion (MVM) were significantly more frequent in HDP-FGR and early FGR (92% and 83%). MVM were significantly associated with abnormal feto-placental Doppler parameters, especially in early FGR. Delayed villous maturation (DVM) was associated with late FGR (83%). HDP-AGA fetus cases presented a heterogeneous pattern of placental lesions, including 60% of cases with MVM, but were not associated with abnormal Doppler feto-placental velocimetry. Conclusions: We found a prevalence of placental maternal vascular malperfusion in HDP-FGR and early FGR groups. These lesions were also associated with abnormal, anti-, and angiogenic markers. Conversely HDP-AGA fetus and late FGR presented more heterogeneous placental lesions not severe enough to cause feto-placental Doppler anomalies. These conditions are likely associated with different etiologies, such as maternal pre-pregnancy risk factors for metabolic syndrome. These findings suggest a possible preventive nutritional approach in addition to low-dose aspirin in pregnant women with predisposing factors for HDP-AGA fetuses and late FGR.

Introduction A potential complication of term prelabor rupture of membranes (term PROM) is chorioamnionitis with an increased burden on neonatal outcomes of chronic lung disease and cerebral palsy. The purpose of the study was to analyze the efficacy of a standing clinical protocol designed to identify women with term PROM at low risk for chorioamnionitis, who may benefit from expectant management, and those at a higher risk for chorioamnionitis, who may benefit from early induction. Material and methods This retrospective study enrolled all consecutive singleton pregnant women with term PROM. Subjects included women with at least one of the following factors: white blood cell count ≥ 15×100/μL, C-reactive protein ≥ 1.5 mg/dL, or positive vaginal swab for beta-hemolytic streptococcus. These women comprised the high risk (HR) group and underwent immediate induction of labor by the administration of intravaginal dinoprostone. Women with none of the above factors and those with a low risk for chorioamnionitis waited for up to 24 hours for spontaneous onset of labor and comprised the low-risk (LR) group. Results Of the 884 consecutive patients recruited, 65 fulfilled the criteria for HR chorioamnionitis and underwent immediate induction, while 819 were admitted for expectant management. Chorioamnionitis and Cesarean section rates were not significantly different between the HR and LR groups. However, the prevalence of maternal fever (7.7% vs. 2.9%; p = 0.04) and meconium-stained amniotic fluid was significantly higher in the HR group than in LR group (6.1% vs. 2.2%; p = 0.04). This study found an overall incidence of 4.2% for chorioamnionitis, 10.9% for Cesarean section, 0.5% for umbilical artery blood pH < 7.10, and 1.9% for admission to the neonatal intensive care unit. Furthermore, no confirmed cases of neonatal sepsis were encountered. Conclusions A clinical protocol designed to manage, by immediate induction, only those women with term PROM who presented with High Risk factors for infection/inflammation achieved similar maternal and perinatal outcomes between such women and women without any risks who received expectant management. This reduced the need for universal induction of term PROM patients, thereby reducing the incidence of maternal and fetal complications without increasing the rate of Cesarean sections.

In survival analysis, time-varying covariates are endogenous when their measurements are directly related to the event status and incomplete information occur at random points during the follow-up. Consequently, the time-dependent Cox model leads to biased estimates. Joint models (JM) allow to correctly estimate these associations combining a survival and longitudinal sub-models by means of a shared parameter (i.e., random effects of the longitudinal sub-model are inserted in the survival one). This study aims at showing the use of JM to evaluate the association between a set of inflammatory biomarkers and Covid-19 mortality. During Covid-19 pandemic, physicians at Istituto Clinico di Città Studi in Milan collected biomarkers (endogenous time-varying covariates) to understand what might be used as prognostic factors for mortality. Furthermore, in the first epidemic outbreak, physicians did not have standard clinical protocols for management of Covid-19 disease and measurements of biomarkers were highly incomplete especially at the baseline. Between February and March 2020, a total of 403 COVID-19 patients were admitted. Baseline characteristics included sex and age, whereas biomarkers measurements, during hospital stay, included log-ferritin, log-lymphocytes, log-neutrophil granulocytes, log-C-reactive protein, glucose and LDH. A Bayesian approach using Markov chain Monte Carlo algorithm were used for fitting JM. Independent and non-informative priors for the fixed effects (age and sex) and for shared parameters were used. Hazard ratios (HR) from a (biased) time-dependent Cox and joint models for log-ferritin levels were 2.10 (1.67-2.64) and 1.73 (1.38-2.20), respectively. In multivariable JM, doubling of biomarker levels resulted in a significantly increase of mortality risk for log-neutrophil granulocytes, HR=1.78 (1.16-2.69); for log-C-reactive protein, HR=1.44 (1.13-1.83); and for LDH, HR=1.28 (1.09-1.49). Increasing of 100 mg/dl of glucose resulted in a HR=2.44 (1.28-4.26). Age, however, showed the strongest effect with mortality risk starting to rise from 60 years.

Background Alcohol and tobacco are the major risk factors for oral and pharyngeal cancer, but diet is likely to have a role, too. Objective The objective was to analyze the relationship between adherence to the 2015-2020 Dietary Guidelines for Americans (DGA), as measured by the Healthy Eating Index 2015 (HEI-2015), and oral and pharyngeal cancer risk. Moreover, this work aimed to quantify the number of avoidable cases under different scenarios of increased adherence to the DGA, with the use of the potential impact fraction. This estimates the proportion of cases that would occur if the distribution of the risk factor in the population followed an alternative distribution. Design A multicenter, case–control study was conducted in Italy between 1991 and 2009. Participants’ usual diet for the 2 years preceding study enrolment was assessed using a food frequency questionnaire. Participants and setting Cases were 946 patients admitted to major hospitals with incident, histologically confirmed oral and pharyngeal cancer. Controls were 2,492 patients admitted to the same hospitals for acute non neoplastic conditions. Main outcome measures The adherence to the DGA was assessed using the HEI-2015 score (range = 0 to 100), based on 13 components. The outcome was oral and pharyngeal cancer. Statistical analyses performed Odds ratios and the corresponding 95% CIs were estimated using multiple logistic regression models adjusted for tobacco, alcohol, and other relevant covariates. The potential impact fraction was estimated under different scenarios of adherence to the DGA. Results In this Italian population the HEI-2015 score ranged from 33.4 to 97.5. A higher HEI-2015 score was associated with a lower risk of oral and pharyngeal cancer, with an odds ratio of 0.70 (95% CI 0.62 to 0.79) for a 10-point increment of the score. The estimated potential impact fraction was 64.8% under the maximum achievable reduction scenario, and it ranged from 9% to 27% following other more feasible scenarios. Conclusions The HEI-2015 score was inversely related to oral and pharyngeal cancer risk in this Italian population. This analysis allowed for the estimation of the fraction of preventable cases, under different feasible scenarios. A share of 9% to 27% of avoidable cases of oral and pharyngeal cancer might be obtained across real-world scenarios of adherence to the DGA as measured by the HEI-2015 score.

To explore the role of coffee on health outcomes in the United States, where coffee consumption is common, we conducted a meta-analysis of prospective studies investigating the magnitude (any compared with no consumption) and the dose-response shape (cups per day) of the associations between caffeinated coffee consumption and incidence/mortality of cardiovascular disease (CVD), as well as incidence of type 2 diabetes (T2D), hepatocellular carcinoma (HCC), endometrial cancer, melanoma, and nonmelanoma skin cancer. We selected the desirable health outcomes that have been shown to be positively associated with coffee consumption. Studies were identified by searching PubMed/Embase databases up to September 2019. Inclusion criteria included prospective studies that investigated the relation of ≥3 categories of caffeinated coffee consumption and the outcomes of interest. Twenty-six studies (42 distinct cohorts), with 93,706 cases/deaths and 3,713,932 participants, met the inclusion criteria. In any coffee consumers, there was a significant inverse association with the risk of CVD (RR=0.90; 95% CI: 0.84, 0.96), T2D (RR=0.90; 95% CI: 0.85, 0.96), endometrial cancer (RR=0.85; 95% CI: 0.78, 0.92), melanoma (RR=0.89; 95% CI: 0.80, 0.99), and nonmelanoma skin cancer (RR=0.92; 95% CI: 0.89, 0.95). Coffee consumption was also inversely associated with HCC (RR=0.93; 95% CI: 0.80, 1.08), without reaching statistical significance. The dose-response relation was nonlinear uniquely for CVD (P-nonlinearity=0.01). In particular, the largest risk reduction was observed for 3-4 cups/d (∼120mL/cup) and no reduction thereafter. For other outcomes, the risk decreased linearly over the whole coffee consumption range. Current patterns of consumption in the United States would account for a fraction of avoided cases/deaths ranging from 6% to 12% according to the outcome considered. This study confirms the beneficial health effects of caffeinated coffee consumption in the US population on the health outcomes considered, and quantifies their possible magnitude.

Despite the considerable number of studies investigating the Mediterranean diet in prostate cancer (PCa) etiology, very few focused on cancer survival. We assessed the pre-diagnostic diet and physical activity in a cohort of 777 men with PCa diagnosed between 1995 and 2002 in north-eastern Italy, adherence to the Mediterranean diet was evaluated through the Mediterranean Diet Score (MDS). Hazard ratios (HR) of death with confidence intervals (CI) were estimated using the Cox model, adjusting for potential confounders. During 10 years of follow-up, 208 patients (26.8%) died, 75 (9.7%) due to PCa. Patients reporting MDS &ge, 5 showed a higher overall survival than those with MDS &lt, 5 (HR = 0.74, 95% CI: 0.56&ndash, 0.99). Although high physical activity was not significantly associated with overall survival (HR = 0.79, 95% CI: 0.59&ndash, 1.07), the HR for all-cause death was the lowest (HR = 0.58, 95% CI: 0.38&ndash, 0.90) for men reporting MDS &ge, 5 and high physical activity compared to those reporting MDS &lt, 5 and low/moderate physical activity. No association emerged for PCa specific survival. Study findings support the beneficial impact of pre-diagnostic adherence to the Mediterranean diet and physical activity on overall survival, they are mainly driven by risk reduction in non-prostate cancer mortality, which however accounts for about 80% of death in men with PCa.

Adherence to Mediterranean diet has been consistently associated with a reduced mortality in the general population, but evidence for women with breast cancer is scanty. Methods: A cohort of 1453 women with breast cancer diagnosed between 1991 and 1994 in northern Italy was followed-up for vital status for 15 years after diagnosis. The pre-diagnostic habitual diet was assessed through a structured questionnaire and adherence to the Mediterranean diet was evaluated through the Mediterranean Diet Score. Hazard ratios (HR) of death with confidence intervals (CI) were estimated using Cox model, adjusting for potential confounders. Results: Compared to women who scarcely adhere to the Mediterranean diet (n = 332, 22.8%), those highly adherent (n = 500, 34.4%) reported higher intakes of carbohydrates, mono-unsaturated and poly-unsaturated fatty acids, vitamins, folate, and carotenoids, and lower intakes of cholesterol and animal proteins. Adherence to the Mediterranean diet was associated with a better prognosis: 15-year overall survival of 63.1% for high and 53.6% for low adherence, respectively (p = 0.013). HR for all-cause mortality was 0.72 (95% CI: 0.57&minus, 0.92) and HR for breast cancer mortality was 0.65 (95% CI: 0.43&minus, 0.98) for women 55 years and older. No significant association emerged for breast cancer mortality in the total cohort. Conclusions: Although dietary habits may have changed after breast cancer diagnosis, these findings indicate that women who ate according to the Mediterranean dietary pattern prior to their diagnosis may have greater chance of a favorable prognosis after breast cancer diagnosis compared to those who did not.

Limited knowledge is available on dietary patterns and bladder cancer risk. We analyzed data from an Italian case-control study carried out between 2003 and 2014, including 690 incident bladder cancer cases and 665 hospital-controls. We derived nutrient-based dietary patterns applying principal component factor analysis on 28 selected nutrients. We categorized factor scores according to quartiles, and estimated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) through logistic regression models, adjusted for major confounding factors. We identified four dietary patterns named &ldquo, Animal products&rdquo, &ldquo, Vitamins and fiber&rdquo, Starch-rich&rdquo, and &ldquo, Animal unsaturated fatty acids&rdquo, We found an inverse association between the &ldquo, pattern and bladder cancer (OR = 0.70, 95% CI: 0.48&ndash, 0.99, IV versus I quartile category). Inverse relationships of borderline significance were also found for the &ldquo, and the &ldquo, dietary patterns. No significant association was evident for the &ldquo, pattern. The current study allowed us to identify major dietary patterns in this Italian population. Our study confirms available evidence and shows that scoring high on a fruit-and-vegetables pattern provides beneficial effects on bladder cancer risk.

BACKGROUND: The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) released in 2007 eight recommendations for cancer prevention on body fatness, diet and physical activity. Our aim is to evaluate the relation between adherence to these recommendations and colorectal cancer (CRC) risk. METHODS: We pooled data from two Italian case-control studies including overall 2419 patients with CRC and 4723 controls. Adherence to the WCRF/AICR guidelines was summarised through a score incorporating seven of the WCRF/AICR recommendations, with higher scores indicating higher adherence to the guidelines. Odds ratios (ORs) of colorectal cancer were estimated using multiple logistic regression models. RESULTS: Higher adherence to the WCRF/AICR recommendations was associated with a significantly reduced CRC risk (OR 0.67, 95% confidence interval, CI, 0.56-0.80 for a score ≥5 versus

This study aimed to evaluate the association between personal and job characteristics and the risk of upper limb work-related musculoskeletal disorders (WMSDs) among operating room nurses (ORNs). To this end, we collected data from 148 ORNs working at 8 Italian hospitals and measured any upper limb disabilities experienced in the previous year using the Italian version of the disabilities of the arm, shoulder and hand (DASH) questionnaire. The associations between personal and job characteristics and risk of upper limb WMSDs were estimated by unconditional logistic regression models. The prevalence of upper limb WMSDs was 45.9%. Multivariate analysis showed the &ldquo, female gender&rdquo, and &ldquo, monthly hours spent working as a scrub nurse&rdquo, to be directly associated with a higher DASH score (adjusted OR for gender = 5.37, 95% CI: 1.65&ndash, 17.51, p &lt, 0.01, adjusted OR for monthly hours as scrub nurse = 3.09, 95% CI: 1.33&ndash, 7.19, p &lt, 0.01). Overall, our findings indicate that a full-time job (&gt, 120 h/month) as a scrub nurse significantly increases the risk of developing upper limb WMSDs among female ORNs. Thus, to reduce such risk in this particularly sensitive population, we recommend urgent implementation of ergonomic interventions on surgical equipment alongside job rotation and medical surveillance programs.

Background Since food metabolites are eliminated by the urinary tract, several studies have investigated the association between diet and bladder cancer risk. Recently, the World Cancer Research Fund International/American Institute for Cancer Research (WCRF/AICR) suggested a potential beneficial effect of some foods (mainly vegetables, fruit, and milk) in the development of bladder cancer. We investigated the association between food groups and bladder cancer risk, seeking insights into food diversity as well as meat cooking methods. Methods Data were derived from an Italian multicentre case–control study, conducted between 2003 and 2014, including 690 bladder cancer cases and 665 frequency-matched controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (95%CIs) for various dietary aspects were estimated by unconditional logistic regression models adjusted for energy intake and the major known risk factors for bladder cancer. Results Comparing the highest versus the lowest quartiles, consumption of vegetables (OR = 0.62; 95%CI: 0.44-0.88) and milk/yogurt (OR = 0.62; 95%CI: 0.44–0.87) reduced the risk of bladder cancer. Conversely, consumption of meat increased bladder cancer risk with an OR of 1.57 (95%CI: 1.07–2.31), particularly when the meat was stewed (OR = 1.47; 95%CI: 1.03–2.09) or roasted (OR = 1.41; 95%CI: 1.00–1.99). There was a suggestion that a diversified diet reduced the risk of bladder cancer, but this was not significant. Conclusions Our study consolidates the role of diet in bladder cancer aetiology, showing a reduced risk for vegetable and milk/yogurt consumption and an increased risk for meat consumption, especially when the meat is stewed or roasted.

Objectives The aim of this study was to evaluate whether the association between the inflammatory potential of one's diet and cancer risk varies across age groups in a population characterized by widespread use of the Mediterranean diet. Methods We analyzed data from a network of case-control studies conducted in Italy between 1991 and 2014. The studies included cancers of the oral cavity (n = 509), pharynx (n = 436), nasopharynx (n = 198), larynx (n = 459), esophagus (n = 304), stomach (n = 230), colon (n = 1225), rectum (n = 728), liver (n = 184), pancreas (n = 326), breast (n = 2569), endometrium (n = 454), ovary (n = 1031), prostate (n = 1294), kidney (n = 767), and bladder (n = 690). Controls were 13 563 patients hospitalized for acute, non-neoplastic conditions. Dietary inflammatory index (DII) scores were computed based on 31 food parameters assessed using a reproducible and validated food frequency questionnaire. Odds ratios were estimated through logistic regression models adjusting for recognized confounding factors. Results The DII increased with age, with lower scores among men than women, in individuals located in northern rather than in central or southern Italy, and in controls more than in cancer cases. After adjustment for cancer-specific potential confounders, an increasing DII score was directly associated with cancer risk for all considered cancer sites, except for liver and endometrium. Although the DII level varied across age groups, no heterogeneity in cancer risk emerged for any of the considered cancer sites. Conclusions In the Italian population, DII scores were higher in elderly than in middle-aged individuals. Although not directly affecting cancer risk, this finding may have important implications for the older population because elevated DII scores, indicating a proinflammatory diet, also have been associated with frailty.

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.

Previous studies on the relationship between fluid intake and risk of bladder cancer have generally focused on beverages, and results have been inconsistent. We investigated the relationship between water intake and bladder cancer risk, considering water from both beverages and foods. Between 2003 and 2014 we conducted a multicenter hospital-based case-control study in Italy on 690 cases and 665 frequency-matched controls. Water intake for beverages and foods was computed using the Italian food composition database. Odds ratios (ORs) and the corresponding 95% confidence intervals (95%CIs) for water intake were estimated by unconditional multiple logistic regression models, adjusting for major risk factors for bladder cancer. In the control group, the 64.7% of water intake derived from beverages and 35.4% from foods. Comparing the highest with the lowest quartile of intake, water from beverages (OR=1.14; 95%CI: 0.82-1.59) and water from foods (OR=0.88; 95%CI: 0.61-1.28) were not significantly associated with bladder cancer risk. Some specific water sources showed significant associations with bladder cancer risk (e.g. water from vegetables, OR=0.58; 95%CI: 0.40-0.86). However, these associations may be due to the effect of other components contained in beverages and foods rather than to the water content itself. Considering the intakes of water from both beverages and foods, total water intake was not associated with bladder cancer risk.

Background: Pancreatic cancer is a leading cause of cancer death. A role of dietary factors in pancreatic carcinogenesis has been suggested. The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) published 8 recommendations for cancer prevention. We evaluated the effect of adherence to the WCRF/AICR recommendations on pancreatic cancer risk. Methods: We operationalized 7 of the 8 WCRF/AICR recommendations to generate a WCRF/AICR score. We examined the association of WCRF/AICR score with pancreatic cancer in data from an Italian case-control study of 326 incident cases and 652 controls. Results: Adherence to WCRF/AICR recommendations was associated with a significantly decreased risk of pancreatic cancer. Using a WCRF/AICR score

Previous studies have reported that Mediterranean diet is inversely related to the risk of several neoplasms, however, limited epidemiological data are available for bladder cancer. Thus, we examined the association between Mediterranean diet and this neoplasm in an Italian multicentric case-control study consisting of 690 bladder cancer cases and 665 controls. We assessed the adherence to the Mediterranean diet via a Mediterranean Diet Score (MDS), which represents the major characteristics of the Mediterranean diet and ranges from 0 to 9 (from minimal to maximal adherence, respectively). We derived odds ratios (ORs) of bladder cancer according to the MDS score from multiple logistic regression models, allowing for major confounding factors. The ORs of bladder cancer were 0.72 (95% confidence interval, CI, 0.54&ndash, 0.98) for MDS of 4&ndash, 5 and 0.66 (95% CI, 0.47&ndash, 0.93) for MDS of 6&ndash, 9 (p for trend = 0.02) compared to MDS = 0&ndash, 3. Results were similar in strata of sex, age, and education, while the risk appeared somewhat lower in never-smokers and patients with pT1&ndash, pT4 bladder carcinomas. Among individual components of the MDS, we observed inverse associations for greater consumption of legumes, vegetables, and fish. In our study, which was carried out on an Italian population, the higher adherence to the Mediterranean diet was related to a lower risk of bladder cancer.

Bank employees, especially video display terminal (VDT) operators, are constantly exposed to various occupational risks, such as the adoption of awkward postures, repetitive finger movements, and utilization of software with poor usability, which may lead to computer visual syndrome, tension headache, lower back pain, and/or stress, which compromises their overall health and work ability (WA). Thus, in this cross-sectional study, we aimed to establish that the determinants among socio-demographic, lifestyle, and occupational characteristics are associated with impaired WA in bank VDT operators. To this end, we administered a set of socio-demographic, lifestyle, occupational, and Work Ability Index (WAI) questionnaires to 2077 Italian bank VDT operators. Univariate linear regression models reveal that their mean WAI score is inversely associated with gender, age, dependent family members, and a part-time job, whereas it is directly associated with the educational level and physical activity. In addition, multivariate analysis shows that their mean WAI score is inversely associated with age and a part-time job, but was directly associated with the educational level, the marital status, and physical activity. Overall, VDT operators working in Italian banks display high WA even though this latter tends to decline with aging. In light of the progressive aging of the workforce in Italy, our results provide the rationale for the design of interventions aimed to mitigate the detrimental effects of aging on WA of bank VDT operators.

Neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase (MMP)-9, and NGAL/MMP-9 complex have been evaluated as diagnostic markers of several cancers, but results for bladder cancer are scanty. We evaluated these proteins in urine and serum of 89 patients with histologically confirmed bladder cancer and 119 cancer-free controls from a case-control study. Urinary concentrations were standardized on creatinine level. The performance of these proteins as cancer biomarkers was evaluated through the receiver operating characteristic (ROC) analysis. Urinary level of NGAL, MMP-9, and NGAL/MMP-9 complex was higher in current smokers, whereas no impact of dietary habits was observed. After adjusting for tobacco smoking, urinary concentration of MMP-9 was independently associated with cancer invasiveness, grading, and histological subtype, with elevated concentrations among T2-T4 and non-papillary bladder cancers. Conversely, NGAL and NGAL/MMP-9 complex were significantly higher in non-papillary than in papillary subtype. The pattern was less clear in serum, but correlation between urinary and serum concentration was poor, especially for Ta/is-T1 tumors. The ROC analysis confirmed that MMP-9 was the best marker (area under the ROC curve (AUC) = 0.68). Performances were much greater for muscle-invasive bladder cancers (AUC = 0.90), with elevated negative predictive values (97 %). The present study suggests that NGAL/MMP-9 pathway is associated with an aggressive phenotype of bladder cancer. The elevated negative predictive value of MMP-9 and NGAL/MMP-9 complex makes them candidate markers of exclusion test for bladder cancer. These proteins may be integrated in the surveillance of bladder cancer, thus diminishing patients' discomfort and improving compliance.

Background The Metabolic syndrome (MetS) is an emerging condition worldwide, consistently associated with an increased risk of several cancers. Some information exists on urothelial carcinoma of the bladder (UCB) and MetS. This study aims at further evaluating the association between the MetS and UCB. Methods Between 2003 and 2014 in Italy, we conducted a hospital-based case-control study, enrolling 690 incident UCB patients and 665 cancer-free matched patients. The MetS was defined as the presence of at least three of the four selected indicators: abdominal obesity, hypercholesterolemia, hypertension, and diabetes. Odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) for MetS and its components were estimated through multiple logistic regression models, adjusting for potential confounders. Results Patients with MetS were at a 2-fold higher risk of UCB (95 % CI:1.38–3.19), compared to those without the MetS. In particular, ORs for bladder cancer were 2.20 (95 % CI:1.42–3.38) for diabetes, 0.88 (95 % CI: 0.66-1.17) for hypertension, 1.16 (95 % CI: 0.80-1.67) for hypercholesterolemia, and 1.63 (95 % CI:1.22–2.19) for abdominal obesity. No heterogeneity in risks emerged across strata of sex, age, education, geographical area, and smoking habits. Overall, 8.1 % (95 % CI: 3.9-12.4 %) of UCB cases were attributable to the MetS. Conclusions This study supports a positive association between the MetS and bladder cancer risk.

Regular aspirin use has been associated to decreased risk of several cancers, but evidence on nasopharyngeal carcinoma is scanty. We conducted a hospital-based case-control study in Italy, enrolling 198 Caucasian patients with nasopharyngeal carcinoma. Controls were 592 cancer-free Caucasian patients admitted to the same catchment areas as cases; controls were frequency matched according to sex, age, and area of residence. Regular aspirin use was defined as taking at least one aspirin a week for at least 6 months. Three cases (1.5%) and 27 controls (4.5%) reported regular aspirin use (odds ratio = 0.24; 95% CI: 0.07–0.87). The median duration of consumption was 15 months among cases and 60 months among controls. Although study findings should be considered with caution due to limited sample size, they provide further evidence on the protective effect of aspirin use in head and neck cancers.

Purpose To prospectively assess the survival, patterns of failure, and prognostic factors in a large cohort of patients with malignant pleural mesothelioma who had undergone a novel trimodal therapeutic approach, including lung-sparing surgery, chemotherapy, and subsequent treatment with high doses of intensity modulated radiation therapy (IMRT) to the whole hemithorax. Methods and Materials The analysis was conducted on the data from 69 patients. Of the 69 patients, 35 underwent extended pleurectomy/decortication (P/D), with resection of the entire pleura, along with portions of the pericardium and diaphragm and 34, partial pleurectomy, defined as partial removal of parietal or visceral pleura for diagnostic purposes, leaving gross tumor behind in all cases. All patients received cisplatin/pemetrexed chemotherapy. Postoperative IMRT was delivered to the entire hemithorax, excluding the intact lung. The IMRT dose was 50 Gy in 25 fractions. Any fluorodeoxyglucose-avid areas or regions of particular concern for residual disease were given a simultaneous boost to 60 Gy. Results The median follow-up duration was 19 months. No difference was seen in overall survival and locoregional control between the extended P/D group and the partial pleurectomy group. The 2-year overall survival was 65% and 58% in the extended P/D and partial pleurectomy groups, respectively ( P =.94). Locoregional control at 2 years was 65% and 64% in the extended P/D and partial pleurectomy groups, respectively ( P =.75). The predominant pattern of failure was distant: 19 patients (27.5%) developed distant metastases as the first site of relapse. Gross residual disease after surgery was significantly associated with overall survival (hazard ratio 3.45). One fatal pneumonitis was reported; 14 cases (20%) of grade 2 to 3 pneumonitis were documented. Conclusions Radical IMRT after lung-sparing surgery and chemotherapy for malignant pleural mesothelioma leads to promising survival results and acceptable toxicity rates. The similarity of survival between patients treated with extended P/D or partial pleurectomy observed in our study is intriguing.

To evaluate the impact of tobacco smoking on specific histological subtypes of transitional cell carcinoma of the bladder (TCC). Between 2003 and 2009, we conducted a hospital-based case-control study in Italy, enrolling 531 incident TCC cases and 524 cancer-free matched patients. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were estimated through multiple logistic regression models. Compared to never smokers, TCC risk was threefold higher in former smokers (95% CI 2.07–4.18) and more than sixfold higher in current smokers (95% CI 4.54–9.85). TCC risk steadily increased with increasing intensity (OR for ≥25 cigarettes/day 8.75; 95% CI 3.40–22.55) and duration of smoking (OR for ≥50 years 5.46; 95% CI 2.60–11.49). No heterogeneity emerged between papillary and non-papillary TCCs for smoking intensity and duration, but the risk for those who had smoked for ≥50 years was twice for non-papillary TCC (OR 10.88) compared with papillary one (OR 4.76). Among current smokers, the risk for a 10-year increase in duration grew across strata of intensity (p-trend = 0.046). Conversely, the risk for a 5-cigarette/day increase in smoking intensity was quite steady across strata of duration (p-trend = 0.18). Study results suggested that duration of smoking outweighs intensity in determining TCC risk, with limited differences across histological subtypes. Elimination of tobacco smoking may prevent about 65 % of TCCs.

This paper introduces rpartScore (Galimberti, Soffritti, and Di Maso 2012), a new R package for building classification trees for ordinal responses, that can be employed whenever a set of scores is assigned to the ordered categories of the response. This package has been created to overcome some problems that produced unexpected results from the package rpartOrdinal (Archer 2010). Explanations for the causes of these unexpected results are provided. The main functionalities of rpartScore are described, and its use is illustrated through some examples.

Autologous stem cell transplantation (ASCT) is a feasible procedure for human immunodeficiency virus-1 (HIV-1) lymphoma patients, whose underlying disease and intrinsic HIV-1- and ASCT-associated immunodeficiency might increase the risk for γ-herpesvirus load persistence and/or reactivation. We evaluated this hypothesis by investigating the levels of Epstein-Barr virus (EBV)- and Kaposi sarcoma-associated herpesvirus (KSHV)-DNA levels in the peripheral blood of 22 HIV-1-associated lymphoma patients during ASCT, highlighting their relationship with γ-herpesvirus lymphoma status, immunological parameters, and clinical events. EBV-DNA was detected in the pre-treatment plasma and peripheral blood mononuclear cells (PBMCs) of 12 (median 12,135 copies/mL) and 18 patients (median 417 copies/10(6) PBMCs), respectively; the values in the two compartments were correlated (r = 0.77, p = 0.0001). Only EBV-positive lymphomas showed detectable levels of plasma EBV-DNA. After debulking chemotherapy, plasma EBV-DNA was associated with lymphoma chemosensitivity (p = 0.03) and a significant higher mortality risk by multivariate Cox analysis adjusted for EBV-lymphoma status (HR, 10.46, 95% CI, 1.11-98.32, p = 0.04). After infusion, EBV-DNA was detectable in five EBV-positive lymphoma patients who died within six months. KSHV-DNA load was positive in only one patient, who died from primary effusion lymphoma. Fluctuations in levels of KSHV-DNA reflected the patient's therapy and evolution of his underlying lymphoma. Other γ-herpesvirus-associated malignancies, such as multicentric Castleman disease and Kaposi sarcoma, or end-organ complications after salvage treatment were not found. Overall, these findings suggest a prognostic and predictive value of EBV-DNA and KSHV-DNA, the monitoring of which could be a simple, complementary tool for the management of γ-herpesvirus-positive lymphomas in HIV-1 patients submitted to ASCT.