Publications by authors named "E Negri"

1,132 Publications

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Case Report: Irreversible Watery Diarrhea, Severe Metabolic Acidosis, Hypokalemia and Achloridria Syndrome Related to Vasoactive Intestinal Peptide Secreting Malignant Pheochromocytoma.

Front Endocrinol (Lausanne) 2021 17;12:652045. Epub 2021 Mar 17.

Centro Ipertensione Arteriosa e Studio Malattie Cardiorenali, S.S. Fisiopatologia Medica, Clinica Medica Generale e Terapia Medica, Parma, Italy.

Background: Pheochromocytoma (PHEO) clinical manifestations generally mirror excessive catecholamines secretion; rarely the clinical picture may reflect secretion of other hormones. Watery diarrhea, hypokalemia and achlorhydria (WDHA) is a rare syndrome related to excessive secretion of vasoactive intestinal peptide (VIP).

Clinical Case: A 73-year-old hypotensive man affected by adrenal PHEO presented with weight loss and watery diarrhea associated with hypokalemia, hyperchloremic metabolic acidosis (anion gap 15 mmol/l) and a negative urinary anion gap. Abdominal computed tomography scan showed a right adrenal PHEO, 8.1 cm in maximum diameter, with tracer uptake on GaDOTA-octreotate positron emission tomography. Metastasis in lumbar region and lung were present. Both chromogranin A and VIP levels were high (more than10 times the normal value) with slightly elevated urine normetanephrine and metanephrine excretion. Right adrenalectomy was performed and a somatostatin analogue therapy with lanreotide started. Immunostaining showed chromogranin A and VIP co-expression, with weak somatostatin-receptor-2A positivity. In two months, patient clinical conditions deteriorated with severe WDHA and multiple liver and lung metastasis. Metabolic acidosis and hypokalemia worsened, leading to hemodynamic shock and exitus.

Conclusions: A rare case of WDHA syndrome caused by malignant VIP-secreting PHEO was diagnosed. High levels of circulating VIP were responsible of the rapidly evolving clinical picture with massive dehydration and weight loss along with severe hyperchloremic metabolic acidosis and hypokalemia due to the profuse untreatable diarrhea. The rescue treatment with lanreotide was unsuccessful because of the paucity of somatostatin-receptor-2A on VIP-secreting PHEO chromaffin cells.
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http://dx.doi.org/10.3389/fendo.2021.652045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010837PMC
March 2021

Coagulopathy of hospitalised COVID-19: A Pragmatic Randomised Controlled Trial of Therapeutic Anticoagulation versus Standard Care as a Rapid Response to the COVID-19 Pandemic (RAPID COVID COAG - RAPID Trial): A structured summary of a study protocol for a randomised controlled trial.

Trials 2021 Mar 10;22(1):202. Epub 2021 Mar 10.

St. Michael's Hospital, Applied Health Research Centre, Li Ka Shing Knowledge Institute, University of Toronto, Toronto, Canada.

Objectives: To determine the effect of therapeutic anticoagulation, with low molecular weight heparin (LMWH) or unfractionated heparin (UFH, high dose nomogram), compared to standard care in hospitalized patients admitted for COVID-19 with an elevated D-dimer on the composite outcome of intensive care unit (ICU) admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death up to 28 days.

Trial Design: Open-label, parallel, 1:1, phase 3, 2-arm randomized controlled trial PARTICIPANTS: The study population includes hospitalized adults admitted for COVID-19 prior to the development of critical illness. Excluded individuals are those where the bleeding risk or risk of transfusion would generally be considered unacceptable, those already therapeutically anticoagulated and those who have already have any component of the primary composite outcome. Participants are recruited from hospital sites in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and the United States of America. The inclusion criteria are: 1) Laboratory confirmed COVID-19 (diagnosis of SARS-CoV-2 via reverse transcriptase polymerase chain reaction as per the World Health Organization protocol or by nucleic acid based isothermal amplification) prior to hospital admission OR within first 5 days (i.e. 120 hours) after hospital admission; 2) Admitted to hospital for COVID-19; 3) One D-dimer value above the upper limit of normal (ULN) (within 5 days (i.e. 120 hours) of hospital admission) AND EITHER: a. D-Dimer ≥2 times ULN OR b. D-Dimer above ULN and Oxygen saturation ≤ 93% on room air; 4) > 18 years of age; 5) Informed consent from the patient (or legally authorized substitute decision maker). The exclusion criteria are: 1) pregnancy; 2) hemoglobin <80 g/L in the last 72 hours; 3) platelet count <50 x 10/L in the last 72 hours; 4) known fibrinogen <1.5 g/L (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation); 5) known INR >1.8 (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation); 6) patient already prescribed intermediate dosing of LMWH that cannot be changed (determination of what constitutes an intermediate dose is to be at the discretion of the treating clinician taking the local institutional thromboprophylaxis protocol for high risk patients into consideration); 7) patient already prescribed therapeutic anticoagulation at the time of screening [low or high dose nomogram UFH, LMWH, warfarin, direct oral anticoagulant (any dose of dabigatran, apixaban, rivaroxaban, edoxaban)]; 8) patient prescribed dual antiplatelet therapy, when one of the agents cannot be stopped safely; 9) known bleeding within the last 30 days requiring emergency room presentation or hospitalization; 10) known history of a bleeding disorder of an inherited or active acquired bleeding disorder; 11) known history of heparin-induced thrombocytopenia; 12) known allergy to UFH or LMWH; 13) admitted to the intensive care unit at the time of screening; 14) treated with non-invasive positive pressure ventilation or invasive mechanical ventilation at the time of screening; 15) Imminent death according to the judgement of the most responsible physician; 16) enrollment in another clinical trial of antithrombotic therapy involving hospitalized patients.

Intervention And Comparator: Intervention: Therapeutic dose of LMWH (dalteparin, enoxaparin, tinzaparin) or high dose nomogram of UFH. The choice of LMWH versus UFH will be at the clinician's discretion and dependent on local institutional supply. Comparator: Standard care [thromboprophylactic doses of LMWH (dalteparin, enoxaparin, tinzaparin, fondaparinux)] or UFH. Administration of LMWH, UFH or fondaparinux at thromboprophylactic doses for acutely ill hospitalized medical patients, in the absence of contraindication, is generally considered standard care.

Main Outcomes: The primary composite outcome of ICU admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death at 28 days. Secondary outcomes include (evaluated up to day 28): 1. All-cause death 2. Composite of ICU admission or all-cause death 3. Composite of mechanical ventilation or all-cause death 4. Major bleeding as defined by the ISTH Scientific and Standardization Committee (ISTH-SSC) recommendation; 5. Red blood cell transfusion (>1 unit); 6. Transfusion of platelets, frozen plasma, prothrombin complex concentrate, cryoprecipitate and/or fibrinogen concentrate; 7. Renal replacement therapy; 8. Hospital-free days alive; 9. ICU-free days alive; 10. Ventilator-free days alive; 11. Organ support-free days alive; 12. Venous thromboembolism (defined as symptomatic or incidental, suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); 13. Arterial thromboembolism (defined as suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); 14. Heparin induced thrombocytopenia; 15. Trajectories of COVID-19 disease-related coagulation and inflammatory biomarkers.

Randomisation: Randomisation will be stratified by site and age (>65 versus ≤65 years) using a 1:1 computer-generated random allocation sequence with variable block sizes. Randomization will occur within the first 5 days (i.e. 120 hours) of participant hospital admission. However, it is recommended that randomization occurs as early as possible after hospital admission. Central randomization using an interactive web response system will ensure allocation concealment.

Blinding (masking): No blinding involved. This is an open-label trial.

Numbers To Be Randomised (sample Size): 462 patients (231 per group) are needed to detect a 15% risk difference, from 50% in the control group to 35% in the experimental group, with power of 90% at a two-sided alpha of 0.05.

Trial Status: Protocol Version Number 1.4. Recruitment began on May 11, 2020. Recruitment is expected to be completed March 2022. Recruitment is ongoing.

Trial Registration: ClinicalTrials.gov Identifier: NCT04362085 Date of Trial Registration: April 24, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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http://dx.doi.org/10.1186/s13063-021-05076-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943934PMC
March 2021

European cancer mortality predictions for the year 2021 with focus on pancreatic and female lung cancer.

Ann Oncol 2021 04 21;32(4):478-487. Epub 2021 Feb 21.

Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, Milan, Italy.

Background: We predicted cancer mortality statistics for 2021 for the European Union (EU) and its five most populous countries plus the UK. We also focused on pancreatic cancer and female lung cancer.

Materials And Methods: We obtained cancer death certifications and population data from the World Health Organization and Eurostat databases for 1970-2015. We predicted numbers of deaths and age-standardised (world population) rates for 2021 for total cancers and 10 major cancer sites, using a joinpoint regression model. We calculated the number of avoided deaths over the period 1989-2021.

Results: We predicted 1 267 000 cancer deaths for 2021 in the EU, corresponding to age-standardised rates of 130.4/100 000 men (-6.6% since 2015) and 81.0/100 000 for women (-4.5%). We estimated further falls in male lung cancer rates, but still trending upward in women by +6.5%, reaching 14.5/100 000 in 2021. The breast cancer predicted rate in the EU was 13.3/100 000 (-7.8%). The rates for stomach and leukaemias in both sexes and for bladder in males are predicted to fall by >10%; trends for other cancer sites were also favourable, except for the pancreas, which showed stable patterns in both sexes, with predicted rates of 8.1/100 000 in men and 5.6/100 000 in women. Rates for pancreatic cancer in EU men aged 25-49 and 50-64 years declined, respectively, by 10% and 1.8%, while for those aged 65+ years increased by 1.3%. Rates fell for young women only (-3.4%). Over 1989-2021, about 5 million cancer deaths were avoided in the EU27 compared with peak rates in 1988.

Conclusion: Overall cancer mortality continues to fall in both sexes. However, specific focus is needed on pancreatic cancer, which shows a sizeable decline for young men only. Tobacco control remains a priority for the prevention of pancreatic and other tobacco-related cancers, which account for one-third of the total EU cancer deaths, especially in women, who showed less favourable trends.
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http://dx.doi.org/10.1016/j.annonc.2021.01.006DOI Listing
April 2021

Caffeinated Coffee Consumption and Health Outcomes in the US Population: A Dose-Response Meta-Analysis and Estimation of Disease Cases and Deaths Avoided.

Adv Nutr 2021 Feb 11. Epub 2021 Feb 11.

Department of Clinical Sciences and Community Health, Branch of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro," Università degli Studi di Milano, Milan, Italy.

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 (∼120 mL/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.
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http://dx.doi.org/10.1093/advances/nmaa177DOI Listing
February 2021

Exposure to antithyroid drugs and ethylenethiourea and risk of thyroid cancer: a systematic review of the epidemiologic evidence.

Eur J Cancer Prev 2021 Jan 22. Epub 2021 Jan 22.

Department of Clinical Sciences and Community Health, University of Milan Unit of Medical Statistics and Biometry, Fondazione IRCCS Istituto Nazionale Dei Tumori Di Milano Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, Milan, Italy.

Introduction: The thyroid peroxidase inhibiting compounds methimazole, methylthiouracil, propylthiouracil, thiouracil (i.e. 'antithyroid' drugs) and ethylenethiourea have been associated to thyroid tumours in rodents. According to a systematic review by the International Agency for Research on Cancer (IARC) published in 2000, evidence for the human carcinogenicity was inadequate.

Methods: We performed an up-to-date systematic review of human epidemiological studies on the association between such compounds and thyroid cancer incidence or mortality.

Results: The literature research (1999-March 2020) identified four relevant articles. Considering also reports from the previous IARC review, this systematic review considered seven reports (five distinct studies) on antithyroid drugs and two on ethylenethiourea. As for antithyroid drugs, three reports based on different follow-ups gave results from a cohort of patients treated for hyperthyroidism in 1946-1964. In the earlier report, thyroid cancer incidence was higher in patients primarily treated with antithyroid drugs (3.2/1000) than in those originally treated with thyroidectomy (0.34/1000) or radioactive iodine (0.88/1000), which can be explained by the higher frequency of subsequent thyroidectomy, and hence the higher chance of cancer detection, in that group (30 vs. 0.5 and 1.2%). The two subsequent reports found no deaths from thyroid cancer among patients treated exclusively with antithyroid drugs through 1990 and 2014. A nested case-control study found an odds ratio (OR) of thyroid cancer of 2.79 [95% confidence interval (CI), 0.78-10.02, from a 2-year lag analysis] for ≥3 vs. no propylthiouracil prescriptions. The increased risk can be attributed to advanced diagnosis of an underlying cancer, as suggested by the stronger association observed in a no-lag analysis (OR, 8.03). In a historical cohort of newly diagnosed hyperthyroid patients, the hazard ratio for treatment with radioactive iodine vs. thionamides only was 0.45 (95% CI, 0.21-0.99), possibly due to the closer surveillance of patients receiving thionamides only. Two case-control studies did not find any association with the use of antithyroid drugs. As for ethylenethiourea, no thyroid cancer cases were found in a historical cohort of 1929 workers occupationally exposed in a 15-year period and no association with proxies of mancozeb exposure (a fungicide whose main metabolite is ethylenethiourea) was detected in a cohort of >236 000 farmers.

Conclusion: There is no evidence for a relevant role of either antithyroid drugs or ethylenethiourea on thyroid cancer.
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http://dx.doi.org/10.1097/CEJ.0000000000000658DOI Listing
January 2021

Trends in male breast cancer mortality: a global overview.

Eur J Cancer Prev 2021 Jan 18. Epub 2021 Jan 18.

Department of Clinical Sciences and Community Health Department of Biomedical and Clinical Sciences L. Sacco, Università degli Studi di Milano, Milan, Italy Department of Epidemiology and Health Services Research, Centre for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA.

Objectives: Recent trends in male breast cancer have been inadequately studied. We updated mortality trends in selected countries and regions worldwide using most recent available data and we predicted figures for 2020.

Methods: We extracted official death certification data for male breast cancer and population estimates from the WHO and the Pan American Health Organization databases, from 2000 to 2017. We computed age-standardized (world population) death rates for selected countries and regions worldwide. We used joinpoint regression analysis to identify significant changes in trends and to predict death numbers and rates for 2020.

Results: In 2015-2017, Central-Eastern Europe had a rate of 2.85/1 000 000, and Russia of 2.22, ranking among the highest. North-Western and Southern Europe, the European Union as a whole and the USA showed rates ranging between 1.5 and 2.0. Lower rates were observed in most Latin American countries, with values below 1.35/1 000 000, in Australia, 1.22, and Japan, 0.58. Between 2000-2004 and 2015-2017, age-adjusted death rates decreased between 10 and 40% in North-Western Europe, Russia, and the USA, and between 1.5 and 25% in the other areas under study, except Latin America (+0.8%). Except for Central-Eastern Europe, predicted rates for 2020 were favourable.

Conclusion: Advancements in management are likely the main drivers of the favourable trends in male breast cancer death rates over the last decades. Delayed diagnosis and limited access to effective care explain the higher mortality in some areas.
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http://dx.doi.org/10.1097/CEJ.0000000000000651DOI Listing
January 2021

Colorectal Cancer Mortality in Young Adults Is Rising in the United States, Canada, United Kingdom, and Australia but Not in Europe and Asia.

Gastroenterology 2021 Apr 6;160(5):1860-1862.e2. Epub 2021 Jan 6.

Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2020.12.070DOI Listing
April 2021

Obstetric and neonatal outcomes in women with pregnancy associated cancer: a population-based study in Lombardy, Northern Italy.

BMC Pregnancy Childbirth 2021 Jan 7;21(1):31. Epub 2021 Jan 7.

National Centre for Healthcare Research and Pharmacoepidemiology, Milan, Italy.

Background: Pregnancy associated cancer (PAC) may lead to adverse obstetric and neonatal outcomes. This study aims to assess the association between PACs and adverse perinatal outcomes [i.e. labor induction, iatrogenic delivery, preterm birth, small for gestational age (SGA) newborn, low Apgar score, major malformations, perinatal mortality] in Lombardy, Northern Italy.

Methods: This population-based historic cohort study used the certificate of delivery assistance and the regional healthcare utilization databases of Lombardy Region to identify beneficiaries of National Health Service who delivered between 2008 and 2017. PACs were defined through oncological ICD-9-CM codes reported in the hospital discharge forms. Each woman with PAC was matched to four women randomly selected from those cancer-free (1:4). Log-binomial regression models were fitted to estimate crude and adjusted prevalence ratio (aPR) and the corresponding 95% confidence interval (CI) of each perinatal outcome among PAC and cancer-free women.

Results: Out of the 657,968 deliveries, 831 PACs were identified (1.26 per 1000). PAC diagnosed during pregnancy was positively associated with labor induction or planned delivery (aPR=1.80, 95% CI: 1.57-2.07), cesarean section (aPR=1.78, 95% CI: 1.49-2.11) and premature birth (aPR=6.34, 95% CI: 4.59-8.75). No association with obstetric outcomes was found among PAC diagnosed in the post-pregnancy. No association of PAC, neither during pregnancy nor in post-pregnancy was found for SGA (aPR=0.71, 95% CI: 0.36-1.35 and aPR=1.04, 95% CI: 0.78-1.39, respectively), but newborn among PAC women had a lower birth weight (p-value< 0.001). Newborns of women with PAC diagnosed during pregnancy had a higher risk of borderline significance of a low Apgar score (aPR=2.65, 95% CI: 0.96-7.33) as compared to cancer-free women.

Conclusion: PAC, especially when diagnosed during pregnancy, is associated with iatrogenic preterm delivery, compromising some neonatal heath indicators.
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http://dx.doi.org/10.1186/s12884-020-03508-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791735PMC
January 2021

Cigarettes smoking and androgen receptor-positive breast cancer.

Eur J Cancer Prev 2020 Dec 23;Publish Ahead of Print. Epub 2020 Dec 23.

Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan Piedmont Cancer Registry, A.O.U, Citta` della Salute e della Scienza di Torino Fondo Elena Moroni for Oncology, Turin Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, Milan, Italy.

Objectives: Cigarette smoking is related to higher levels of circulating androgens, but its association with androgen receptor (AR) status is still unaddressed.

Methods: We analysed, with a case-only approach, smoking habits according to AR status in 112 cases of invasive female breast cancer, from the Piedmont Cancer Registry. We used a multivariate logistic regression model to estimate the odds ratio (OR) and the corresponding confidence interval (CI).

Results: The OR of AR-positive breast cancer (versus AR-negative) for ever smokers (versus never) was 2.85 (95% CI 1.02-7.96).

Conclusion: Smoking is related to AR-positive breast cancer.
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http://dx.doi.org/10.1097/CEJ.0000000000000661DOI Listing
December 2020

Attitudes towards influenza vaccine and a potential COVID-19 vaccine in Italy and differences across occupational groups, September 2020.

Med Lav 2020 Nov 17;111(6):445-448. Epub 2020 Nov 17.

BDA DOXA, Milan, Italy.

Objectives: We aimed at describing the attitudes towards influenza vaccination and a potential COVID-19 vaccine in Italy.

Methods: A nationally representative survey based on 1055 Italians aged 15-85 years was conducted in September 16-28, 2020.

Results: We found that 40.8% of the population reported the intention to be vaccinated against influenza next winter and 53.7% would accept to receive a potential COVID-19 vaccine. The percentages were higher among individuals aged 55 and over (58.8% for influenza vaccine and 58.2% for a potential COVID-19 vaccine) and among professionals, managers and teachers as compared to manual workers and farmers (36.1% vs. 27.6% for influenza vaccine and 51.6% vs. 44.8% for a potential COVID-19 vaccine).

Discussion: These data confirm a certain degree of vaccine mistrust in Italy, especially among less qualified workers.
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http://dx.doi.org/10.23749/mdl.v111i6.10813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809985PMC
November 2020

Acute-phase reactants during tocilizumab therapy for severe COVID-19 pneumonia.

Clin Exp Rheumatol 2020 Nov-Dec;38(6):1215-1222. Epub 2020 Dec 3.

University of Modena and Reggio Emilia, Modena, and Rheumatology Unit, Azienda USL-IRCCS di Reggio Emilia, Italy.

Objectives: To identify predictors of clinical improvement and intubation/death in tocilizumab-treated severe COVID19, focusing on IL6 and CRP longitudinal monitoring.

Methods: 173 consecutive patients with severe COVID-19 pneumonia receiving tocilizumab in Reggio Emilia province Hospitals between 11 March and 3 June 2020 were enrolled in a prospective cohort study. Clinical improvement was defined as status improvement on a six-category ordinal scale or discharge from the hospital, whichever came first. A composite outcome of intubation/death was also evaluated. CRP and IL-6 levels were determined before TCZ administration (T0) and after 3 (T3), and 7 (T7) days.

Results: At multivariate analysis T0 and T3 CRP levels were negatively associated with clinical improvement (OR 0.13, CI 0.03-0.55 and OR 0.11, CI 0.0-0.46) (p=0.006 and p=0.003) and positively associated with intubation/death (OR 17.66, CI 2.47-126.14 and OR 5.34, CI: 1.49-19.12) (p=0.01 and p=0.004). No significant associations with IL-6 values were observed. General linear model analyses for repeated measures showed significantly different trends for CRP from day 3 to day 7 between patients who improved and those who did not, and between patients who were intubated or died and those who were not (p<0.0001 for both). ROC analysis identified a baseline CRP level of 15.8 mg/dl as the best cut-off to predict intubation/death (AUC = 0.711, sensitivity = 0.67, specificity = 0.71).

Conclusions: CRP serial measurements in the first week of TCZ therapy are useful in identifying patients developing poor outcomes.
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December 2020

Cancer mortality and predictions for 2020 in selected Australasian countries, Russia and Ukraine.

Eur J Cancer Prev 2021 Jan;30(1):1-14

Department of Clinical Sciences and Community Health.

Objectives: Predicted cancer mortality figures are useful for public health planning. We predicted cancer mortality rates in Israel, Hong Kong, Japan, the Philippines, Korea, Australia, Russia and Ukraine for the year 2020 using the most recent available data. We focused on breast cancer.

Methods: We obtained cancer death certification and population data from the WHO and the United Nations Population Division databases. We derived figures for 10 major cancer sites and total cancers over 1970-2017. We predicted numbers of deaths and age-standardized mortality rates for 2020 through joinpoint regression models. We calculated the number of avoided deaths from 1994-2020.

Results: Overall, total cancer mortality is predicted to decline. Russia had the highest all cancers rates in 2020, 151.9/100 000 men and 79.6 women; the Philippines had the lowest rate in men, 78.0/100 000, Korea in women, 47.5. Stomach cancer rates declined over the whole period in all countries considered, colorectal cancer since the late 1990s. Trends for pancreas were inconsistent. Predicted rates for lung and breast cancer were favourable; women from Hong Kong, Korea and Australia had lung cancer death rates higher than breast ones. Predicted rates for uterine, ovarian, prostate and bladder cancers and leukaemias were downward for most countries. Between 1994 and 2020, over 3.3 million cancer deaths were avoided in the considered countries, except for the Philippines where no reduction was observed.

Conclusion: Predicted cancer rates were lower than in the European Union and the USA, even though falls started later and were less marked.
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http://dx.doi.org/10.1097/CEJ.0000000000000639DOI Listing
January 2021

Dietary patterns and oesophageal cancer: a multi-country latent class analysis.

J Epidemiol Community Health 2020 Nov 17. Epub 2020 Nov 17.

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

Background: The considerable differences in food consumption across countries pose major challenges to the research on diet and cancer, due to the difficulty to generalise and reproduce the dietary patterns identified in a specific population.

Methods: We analysed data from a multicentric case-control study on oesophageal squamous cell carcinoma (ESCC) carried out between 1992 and 2009 in three Italian areas and in the Canton of Vaud, Switzerland, which included 505 cases and 1259 hospital controls. Dietary patterns were derived applying LCA on 24 food groups, controlling for country membership, and non-alcoholic energy intake. A multiple logistic regression model was used to derive odds ratio (ORs) and corresponding 95% CIs for ESCC according to the dietary patterns identified, correcting for classification error.

Results And Conclusion: We identified three dietary patterns. The 'Prudent' pattern was distinguished by a diet rich in fruits and vegetables. The 'Western' pattern was characterised by low consumption of these food groups and higher intakes of sugar. The 'Lower consumers-combination pattern' exhibited a diet poor in most of the nutrients, preferences for fish, potatoes, meat and a few specific types of vegetables. Differences between Italy and Switzerland emerged for pattern sizes and for specific single food preferences. Compared to the 'Prudent' pattern, the 'Western' and the 'Lower consumers-combination' patterns were associated with an increased risk of ESCC (OR=3.04, 95% CI=2.12-4.38 and OR=2.81, 95% CI=1.65-4.76).
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http://dx.doi.org/10.1136/jech-2020-214882DOI Listing
November 2020

Heparin Therapy Improving Hypoxia in COVID-19 Patients - A Case Series.

Front Physiol 2020 19;11:573044. Epub 2020 Oct 19.

Sirio-Libanes Hospital, São Paulo, Brazil.

Introduction: Elevated D-dimer is a predictor of severity and mortality in COVID-19 patients, and heparin use during in-hospital stay has been associated with decreased mortality. COVID-19 patient autopsies have revealed thrombi in the microvasculature, suggesting that hypercoagulability is a prominent feature of organ failure in these patients. Interestingly, in COVID-19, pulmonary compliance is preserved despite severe hypoxemia corroborating the hypothesis that perfusion mismatch may play a significant role in the development of respiratory failure.

Methods: We describe a series of 27 consecutive COVID-19 patients admitted to Sirio-Libanes Hospital in São Paulo-Brazil and treated with heparin in therapeutic doses tailored to clinical severity.

Results: PaO2/FiO2 ratio increased significantly over the 72 h following the start of anticoagulation, from 254(±90) to 325(±80), = 0.013, and 92% of the patients were discharged home within a median time of 11 days. There were no bleeding complications or fatal events.

Discussion: Even though this uncontrolled case series does not offer absolute proof that micro thrombosis in the pulmonary circulation is the underlying mechanism of respiratory failure in COVID-19, patient's positive response to heparinization contributes to the understanding of the pathophysiological mechanism of the disease and provides valuable information for the treatment of these patients while we await the results of further prospective controlled studies.
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http://dx.doi.org/10.3389/fphys.2020.573044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604350PMC
October 2020

Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium.

Int J Cancer 2021 May 17;148(9):2068-2078. Epub 2020 Nov 17.

Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.
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http://dx.doi.org/10.1002/ijc.33360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969437PMC
May 2021

Polyphenol Intake and Gastric Cancer Risk: Findings from the Stomach Cancer Pooling Project (StoP).

Cancers (Basel) 2020 Oct 20;12(10). Epub 2020 Oct 20.

Research Group in Gene-Environment Interactions and Health, Instituto de Biomedicina (IBIOMED), University of León, 24071 León, Spain.

Phenolic compounds may exert a favorable effect on the risk of several cancer types, including gastric cancer (GC). However, selected polyphenol classes have not been adequately investigated in relation to GC. The aim of this study is to evaluate the association between the intake of polyphenols in relation to GC risk. We used data from the Stomach cancer Pooling (StoP) Project, including 10 studies from six countries (3471 GC cases and 8344 controls). We carried out an individual participant data pooled analysis using a two-stage approach. The summary odds ratios (ORs) of GC for each compound, and the corresponding 95% confidence intervals (95% CI), were computed by pooling study specific ORs obtained through multivariate logistic regression, using random effect models. Inverse associations with GC emerged for total polyphenols (OR = 0.67, 95% CI = 0.54-0.81, for the highest versus lowest quartile of intake), total flavonoids (OR = 0.73, 95% CI = 0.55-0.90), anthocyanidins (OR = 0.74, 95% CI = 0.56-0.92), flavanols (OR = 0.77, 95% CI = 0.66-0.88), flavanones (OR = 0.57, 95%CI = 0.44-0.69), total phenolic acids (OR = 0.75, 95%CI = 0.55-0.94), and hydroxybenzoic acids (OR = 0.73, 95%CI = 0.57-0.89). Results were consistent across strata of age, sex, social class, and smoking habit. Suggestive inverse associations were also found for flavonols (OR = 0.76, 95%CI = 0.51-1.01) and hydroxycinnamic acids (OR = 0.82, 95%CI = 0.58-1.06). Further investigations from longitudinal data are needed to confirm this association.
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http://dx.doi.org/10.3390/cancers12103064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588964PMC
October 2020

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial.

J Transl Med 2020 10 21;18(1):405. Epub 2020 Oct 21.

Department of Mental Health and Preventive Medicine, Università degli Studi della Campania Luigi Vanvitelli, Caserta, Italy.

Background: Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.

Methods: A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.

Results: In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P = 0.52) and 22.4% (97.5% CI: 17.2-28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.

Conclusions: Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).
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http://dx.doi.org/10.1186/s12967-020-02573-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576974PMC
October 2020

TOCIVID-19 - A multicenter study on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia. Study protocol.

Contemp Clin Trials 2020 11 6;98:106165. Epub 2020 Oct 6.

Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Napoli, Italy. Electronic address:

Background: Pneumonia is the most frequent complication of COVID-19, due to an aberrant host immune response that is associated with an acute respiratory distress syndrome, and, in most critical patients, with a "cytokine storm". IL-6 might play a key role in the cytokine storm and might be a potential target to treat severe and critical COVID-19. Tocilizumab is a recombinant humanized monoclonal antibody, directed against IL-6 receptor.

Methods: This multicentre study project includes a single-arm phase 2 study and a further parallel cohort, enrolling hospitalized patients with COVID-19 pneumonia and oxygen saturation at rest in ambient air ≤93% or requiring respiratory support. Patients receive tocilizumab 8 mg/kg (up to 800 mg) as one intravenous administration. A second administration (same dose) after 12 h is optional. Two-week and one-month lethality rates are the co-primary endpoints. Sample size planned for the phase 2 study is 330 patients. The parallel cohort will include patients who cannot enter the phase 2 study because being intubated from more than 24 h, or having already received tocilizumab, or the phase 2 study has reached sample size. Primary analysis will include patients enrolled in the phase 2 study. Results of the primary analysis will be validated in the prospective cohort of patients consecutively registered after phase 2 closure from March 20 to March 24, who were potentially eligible for the phase 2 study.

Conclusion: This trial aims to verify the safety and efficacy of tocilizumab in the Italian population with COVID-19 pneumonia and respiratory impairment. EudraCT Number: 2020-001110-38; Clinicaltrials.gov ID NCT04317092.
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http://dx.doi.org/10.1016/j.cct.2020.106165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536129PMC
November 2020

Adult height and risk of gastric cancer: a pooled analysis within the Stomach cancer Pooling Project.

Eur J Cancer Prev 2020 Sep 10. Epub 2020 Sep 10.

Sezione di Igiene, Istituto di Sanità Pubblica, Università Cattolica del Sacro Cuore.

Background: The association between height and risk of gastric cancer has been studied in several epidemiological studies with contrasting results. The aim of this study is to examine the association between adult height and gastric cancer within a large pooled analysis of case-control studies members of the Stomach cancer Pooling (StoP) Project consortium.

Methods: Data from 18 studies members of the StoP consortium were collected and analyzed. A multivariable logistic regression model was used to estimate the study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between 10-cm increase in height and risk of gastric cancer. Age, sex, tobacco smoking, alcohol consumption, social class, geographical area and Helicobacter pylori (H. pylori) status were included in the regression model. Resulting estimates were then pooled with random-effect model. Analyses were conducted overall and in strata of selected variables.

Results: A total of 7562 cases and 19 033 controls were included in the analysis. The pooled OR was 0.96 (95% CI 0.87-1.05). A sensitivity analysis was performed restricting the results to the studies with information on H. pylori status, resulting in an OR of 0.97 (95% CI 0.79-1.20).

Conclusion: Our study does not support a strong and consistent association between adult height and gastric cancer.
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http://dx.doi.org/10.1097/CEJ.0000000000000613DOI Listing
September 2020

Cancer mortality in the oldest old: a global overview.

Aging (Albany NY) 2020 Sep 3;12(17):16744-16758. Epub 2020 Sep 3.

Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Background: As a higher proportion of adults live beyond 85 years, their cancer burden is expected to increase. While trends among the oldest old are established for major epithelial cancers (breast, prostate, lung, and colorectal cancers), they are less studied for minor cancers. This study describes age trends of cancer mortality, with emphasis on individuals aged 85+ years.

Results: Overall cancer mortality peaked at 85 years old and decreased or stabilized for all countries except the USA, France, and Japan, in which mortality continued to increase after age 85 years. For most countries, cancers of the oesophagus, stomach, liver, and larynx have a similar flat trend patterns across all ages. Bladder and kidney cancers as well as non-Hodgkin lymphoma, multiple myeloma, and leukemia showed a decreasing pattern after 85 years for UK, Germany, Italy and Poland. Lung cancer peaked at 80 years, although the age-specific peak among women did not follow the same pattern among all countries. Breast and prostate cancers increased after 85 years.

Conclusion: Mortality stabilized or decreased after age 85, particularly for non-hormonal cancers. Whether this reflects a true biological levelling of mortality rates, or lower validity of cancer registration among the oldest old, remains open to discussion.

Methods: Completed death data were obtained from the World Health Organization (WHO) for eight countries (2000 to 2014). Age-specific mortality rates were calculated for each 5-year age group above age 64. Joinpoint regression models were used to identify significant changes in mortality trends by age.
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http://dx.doi.org/10.18632/aging.103503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521488PMC
September 2020

Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration.

Br J Cancer 2020 10 24;123(9):1456-1463. Epub 2020 Aug 24.

Branch of Medical Statistics, Biometry and Epidemiology "G. A. Maccacaro", Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano, Italy.

Background: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk.

Methods: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking.

Results: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx).

Conclusions: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.
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http://dx.doi.org/10.1038/s41416-020-01031-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592048PMC
October 2020

Feasibility and clinical impact of out-of-ICU noninvasive respiratory support in patients with COVID-19-related pneumonia.

Eur Respir J 2020 Nov 5;56(5). Epub 2020 Nov 5.

Alma Mater Studiorum - Università di Bologna, Dipartimento di Scienze Mediche e Chirurgiche, Infectious Diseases Unit, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

Introduction: The severe acute respiratory syndrome-coronavirus 2 outbreak spread rapidly in Italy and the lack of intensive care unit (ICU) beds soon became evident, forcing the application of noninvasive respiratory support (NRS) outside the ICU, raising concerns over staff contamination. We aimed to analyse the safety of the hospital staff and the feasibility and outcomes of NRS applied to patients outside the ICU.

Methods: In this observational study, data from 670 consecutive patients with confirmed coronavirus disease 2019 referred to pulmonology units in nine hospitals between March 1 and May 10, 2020 were analysed. Data collected included medication, mode and usage of NRS ( high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), noninvasive ventilation (NIV)), length of stay in hospital, endotracheal intubation (ETI) and deaths.

Results: 42 (11.1%) healthcare workers tested positive for infection, but only three of them required hospitalisation. Data are reported for all patients (69.3% male), whose mean±sd age was 68±13 years. The arterial oxygen tension/inspiratory oxygen fraction ratio at baseline was 152±79, and the majority (49.3%) of patients were treated with CPAP. The overall unadjusted 30-day mortality rate was 26.9%, with 16%, 30% and 30% for HFNC, CPAP and NIV, respectively, while the total ETI rate was 27%, with 29%, 25% and 28%, respectively; the relative probability of death was not related to the NRS used after adjustment for confounders. ETI and length of stay were not different among the groups. Mortality rate increased with age and comorbidity class progression.

Conclusions: The application of NRS outside the ICU is feasible and associated with favourable outcomes. Nonetheless, it was associated with a risk of staff contamination.
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http://dx.doi.org/10.1183/13993003.02130-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397952PMC
November 2020

Gallbladder disease, cholecystectomy, and pancreatic cancer risk in the International Pancreatic Cancer Case-Control Consortium (PanC4).

Eur J Cancer Prev 2020 09;29(5):408-415

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

Background: The association among gallbladder disease, cholecystectomy, and pancreatic cancer is unclear. Moreover, time interval between gallbladder disease or cholecystectomy and pancreatic cancer diagnosis is not considered in most previous studies.

Aim: To quantify the association among gallbladder disease, cholecystectomy, and pancreatic cancer, considering time since first diagnosis of gallbladder disease or cholecystectomy.

Methods: We used data from nine case-control studies within the Pancreatic Cancer Case-Control Consortium, including 5760 cases of adenocarcinoma of the exocrine pancreas and 8437 controls. We estimated pooled odds ratios and the corresponding 95% confidence intervals by estimating study-specific odds ratios through multivariable unconditional logistic regression models, and then pooling the obtained estimates using fixed-effects models.

Results: Compared with patients with no history of gallbladder disease, the pooled odds ratio of pancreatic cancer was 1.69 (95% confidence interval, 1.51-1.88) for patients reporting a history of gallbladder disease. The odds ratio was 4.90 (95% confidence interval, 3.45-6.97) for gallbladder disease diagnosed <2 years before pancreatic cancer diagnosis and 1.11 (95% confidence interval, 0.96-1.29) when ≥2 years elapsed. The pooled odds ratio was 1.64 (95% confidence interval, 1.43-1.89) for patients who underwent cholecystectomy, as compared to those without cholecystectomy. The odds ratio was 7.00 (95% confidence interval, 4.13-11.86) for a surgery <2 years before pancreatic cancer diagnosis and 1.28 (95% confidence interval, 1.08-1.53) for a surgery ≥2 years before.

Conclusions: There appears to be no long-term effect of gallbladder disease on pancreatic cancer risk, and at most a modest one for cholecystectomy. The strong short-term association can be explained by diagnostic bias and reverse causation.
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http://dx.doi.org/10.1097/CEJ.0000000000000572DOI Listing
September 2020

Progress in cancer mortality, incidence, and survival: a global overview.

Eur J Cancer Prev 2020 09;29(5):367-381

Department of Clinical Sciences and Community Health.

Cancer mortality has declined over the last three decades in most high-income countries reflecting improvements in cancer prevention, diagnosis, and management. However, there are persisting and substantial differences in mortality, incidence, and survival worldwide. In order to provide an up-to-date overview of trends in mortality, incidence, and survival, we retrieved data from high-quality, population-based cancer registries for all cancers and 10 selected cancer sites in six high-income countries and the European Union. We computed age-standardized (world standard population) mortality and incidence rates, and applied joinpoint regression models. Mortality from all cancers and most common cancer sites has declined over the last 25 years, except for the pancreas and lung (in women). The patterns for incidence are less consistent between countries, except for a steady decrease in stomach cancer in both sexes and lung cancer in men. Survival for all cancers and the selected cancer sites increased in all countries, even if there is still a substantial variability. Although overall cancer death rates continue to decline, incidence rates have been levelling off among men and have been moderately increasing among women. These trends reflect changes in cancer risk factors, screening test use, diagnostic practices, and treatment advances. Many cancers can be prevented or treated effectively if they are diagnosed early. Population-based cancer incidence and mortality data can be used to focus efforts to decrease the cancer burden and regularly monitor progress towards cancer control goals.
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http://dx.doi.org/10.1097/CEJ.0000000000000594DOI Listing
September 2020

A survey on the frequency of COVID-19-like symptoms on students and staff of the University of Milan.

Eur J Cancer Prev 2021 05;30(3):282-284

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

A survey was conducted through a web link on the students and staff of the Università degli Studi di Milano, Italy in the period 14-30 April 2020. It was anonymous at the source and included history of COVID-19-related questions (fever, headache, cold, cough, anosmia, gastrointestinal complaints and separately fever over 38.5°C) in the previous three weeks, and similar information on cohabitants. A total of 14 374 subjects were included. Overall, from 24 March to 30 April, 3138 subjects (21.8%) reported COVID-19-like symptoms, and 219 (1.5%) fever above 38.5°C; 217 subjects performed at least one swab. Of these, 46 were positive (21.3% of those performed, 0.3% of the total). The frequency of any symptom was similar in women and men, but fever above 38.5°C was lower in women (multivariate odds ratio (OR) = 0.65, 95% confidence interval, CI, 0.49-0.85). There was a strong association between symptoms in the respondent and in cohabitants: 64% of subjects with symptoms reported at least one cohabitant with symptoms, compared to 14% of asymptomatic subjects (OR = 11.4, 95% CI, 10.4-12.6). The lower risk of serious symptoms in women, and the strong intra-nucleus of cohabitation contagiousness are an indication that at least part of the symptoms was caused by a new pathogen - SARS-CoV-2. These data, therefore, suggest that the number of persons affected by COVID-19 was much greater in northern Italy than the number of recorded cases. This has implications for the prevention, management and mortality of other serious diseases, including cancer.
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http://dx.doi.org/10.1097/CEJ.0000000000000609DOI Listing
May 2021

Cohort Analysis of Epithelial Cancer Mortality Male-to-Female Sex Ratios in the European Union, USA, and Japan.

Int J Environ Res Public Health 2020 07 23;17(15). Epub 2020 Jul 23.

Department of Clinical Sciences and Community Health, Universitá degli Studi di Milano, 20133 Milan, Italy.

Objective: To illustrate trends in sex ratios in epithelial cancer mortality in the EU, USA, and Japan, with a focus on age-specific and cohort patterns.

Methods: We obtained certified deaths and resident populations from the World Health Organisation for the period of 1970-2014 for the USA, Japan, and the EU for 12 epithelial cancer sites. From these, we calculated both the age-specific and age-standardised male-to-female mortality sex ratios. We applied an age-period-cohort model to the sex ratios in order to disentangle the effects of age, period of death, and birth cohort.

Results: Age-standardised mortality sex ratios were found to be unfavourable to males, apart from thyroid cancer. The highest standardised rates were in laryngeal cancer: 7·7 in the 1970s in the USA, 17·4 in the 1980s in the EU, and 16·8 in the 2000s in Japan. Cohort patterns likely to be due to excess smoking (1890 cohort) and drinking (1940 cohort) in men were identified in the USA, and were present but less defined in the EU and Japan for the oral cavity, oesophagus, liver, pancreas, larynx, lung, bladder, and kidney.

Conclusion: Mortality sex ratio patterns are partly explained by the differences in exposure to known and avoidable risk factors. These are mostly tobacco, alcohol, and obesity/overweight, as well as other lifestyle-related factors.
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http://dx.doi.org/10.3390/ijerph17155311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432705PMC
July 2020

Childhood cancer mortality trends in Europe, 1990-2017, with focus on geographic differences.

Cancer Epidemiol 2020 08 24;67:101768. Epub 2020 Jun 24.

Department of Biomedical and Clinical Sciences L. Sacco, Università degli Studi di Milano, Milan, Italy.

Aim: To monitor trends in childhood cancer mortality in Europe.

Methods: We calculated age-standardized mortality rates per 100,000 children (age 0-14 years) from 1990 to the last available calendar year, for all neoplasms and six main cancers in childhood, in selected European countries and geographic areas, plus the European Union (EU), using data from the World Health Organization database. We carried out a joinpoint regression analysis of mortality trends for all neoplasms, leukaemia and tumours of the nervous system. Results of the joinpoint regression were summarized through annual percent change (APC) for each identified linear segment, and weighted average APC (AAPC) over the whole period.

Results: From 1990 to 2015, childhood total cancer mortality rates dropped by 2.8% per year in the EU, to reach 2.6/100,000 in the latest available calendar years. The greatest declines were in central-eastern countries (AAPCs -3% to -4%). Recent rates ranged between 1.7 and 4.3 deaths/100,000, with the highest values in central-eastern Europe. Leukaemia mortality rates in the EU decreased from 1.6 to 0.6/100,000 in the latest calendar years (AAPC -4%). The deepest declines were registered in central-eastern countries, though they still showed the highest rates (0.9). The lowest leukaemia mortality rates were in northern-western Europe (0.5/100,000), but also in the Czech Republic and Poland. Southern European countries showed comparatively high rates (0.8). Nervous system tumours showed relatively modest falls (AAPC: -1.7% in the EU).

Conclusions: Childhood cancer mortality continued to decline steady in Europe, though geographic differences persist. Further efforts are required to fill the gap, by promoting widespread and rational adoption of currently available treatment protocols.
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http://dx.doi.org/10.1016/j.canep.2020.101768DOI Listing
August 2020

Fruits and vegetables intake and gastric cancer risk: A pooled analysis within the Stomach cancer Pooling Project.

Int J Cancer 2020 12 29;147(11):3090-3101. Epub 2020 Jun 29.

EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal.

A low intake of fruits and vegetables is a risk factor for gastric cancer, although there is uncertainty regarding the magnitude of the associations. In our study, the relationship between fruits and vegetables intake and gastric cancer was assessed, complementing a previous work on the association betweenconsumption of citrus fruits and gastric cancer. Data from 25 studies (8456 cases and 21 133 controls) with information on fruits and/or vegetables intake were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age and the main known risk factors for gastric cancer) odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Exposure-response relations, including linear and nonlinear associations, were modeled using one- and two-order fractional polynomials. Gastric cancer risk was lower for a higher intake of fruits (OR: 0.76, 95% CI: 0.64-0.90), noncitrus fruits (OR: 0.86, 95% CI: 0.73-1.02), vegetables (OR: 0.68, 95% CI: 0.56-0.84), and fruits and vegetables (OR: 0.61, 95% CI: 0.49-0.75); results were consistent across sociodemographic and lifestyles categories, as well as study characteristics. Exposure-response analyses showed an increasingly protective effect of portions/day of fruits (OR: 0.64, 95% CI: 0.57-0.73 for six portions), noncitrus fruits (OR: 0.71, 95% CI: 0.61-0.83 for six portions) and vegetables (OR: 0.51, 95% CI: 0.43-0.60 for 10 portions). A protective effect of all fruits, noncitrus fruits and vegetables was confirmed, supporting further dietary recommendations to decrease the burden of gastric cancer.
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http://dx.doi.org/10.1002/ijc.33134DOI Listing
December 2020

Haemoparasites in red-legged partridge (): first record of sp. in Italy?

J Parasit Dis 2020 Jun 13;44(2):462-466. Epub 2020 Mar 13.

Department of Veterinary Science, University of Turin, V. Leonardo da Vinci 44, 10095 Grugliasco, TO Italy.

During a health survey in the Province of Alessandria (NW Italy) 267 free ranging red-legged partridge (; 137 males and 130 females) were captured in 2009 (n = 101), 2010 (n = 130) and 2011 (n = 36). After biometric data and blood samples collection, animals were released on site. Blood samples were used for the preparation of blood smears. A total of 1.5% of smears presented parasites with a light blue finely granular cytoplasm in red blood cells. The parasites were identified, on the basis of their morphology (no molecular identification was possible), as being sp. juvenile forms. The infestation prevalence was 0.8% in 2010 and 8.3% in 2011. No parasite was observed in 2009. The size of the infested erythrocytes was not altered ( > 0.05) and the nuclear displacement ratio was 0.8 ± 0.2. All the birds were apparently in good health status. To our knowledge this is the first description of sp. in red-legged partridge, and more in general in birds belonging to Galliformes Order in Italy.
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http://dx.doi.org/10.1007/s12639-020-01211-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244661PMC
June 2020

Frequency of Pregnancy-Associated Cancer: A Systematic Review of Population-Based Studies.

Cancers (Basel) 2020 May 26;12(6). Epub 2020 May 26.

Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy.

Despite numerous available resources of evidence, the results about the frequency of pregnancy-associated cancer (PAC) still show poor comparability due to dissimilarities in the study design and methodology, inclusion criteria, incoherent duration of follow-up and a heterogeneous reference population. We conducted a systematic review of population-based studies on PAC published up to December 2019, to provide updated research on this topic, highlighting strengths and limitations. Of the 24 papers included, 11 considered all types of tumors and 13 dealt with specific types of cancer. Differences in the procedures for estimating the frequency of PAC emerged even among population studies. However, we found consistent results for overall frequency of PAC- around 1/1000 pregnancies. Our review suggests that about 25% of PAC cases are diagnosed during pregnancy, confirming the hypothesis of an excess of diagnosis in the postpregnancy period. Sparse and inconsistent results were found regarding a potential increase in the frequency of PAC over calendar years. Alignments in the strategy to identify PAC are needed to overcome methodological weaknesses.
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http://dx.doi.org/10.3390/cancers12061356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352408PMC
May 2020