Ropeginterferon phase 2 randomized study in low-risk polycythemia vera: 5-year drug survival and efficacy outcomes.

In patients with low-risk polycythemia vera, exposure to low-dose Ropeginterferon alfa-2b (Ropeg) 100 µg every 2 weeks for 2 years was more effective than the standard treatment of therapeutic phlebotomy in maintaining target hematocrit (HCT) (< 45%) with a reduction in the need for phlebotomy without disease progression. In the present paper, we analyzed drug survival, defined as a surrogate measure of the efficacy, safety, adherence, and tolerability of Ropeg in patients followed up to 5 years. During the first 2 years, Ropeg and phlebotomy-only (Phl-O) were discontinued in 33% and 70% of patients, respectively, for lack of response (12 in the Ropeg arm vs. 34 in the Phl-O arm) or adverse events (6 vs. 0) and withdrawal of consent in (3 vs. 10). Thirty-six Ropeg responders continued the drug for up to 3 years, and the probability of drug survival after a median of 3.15 years was 59%. Notably, the primary composite endpoint was maintained in 97%, 94%, and 94% of patients still on drug at 3, 4, and 5 years, respectively, and 60% of cases were phlebotomy-free. Twenty-three of 63 Phl-O patients (37%) failed the primary endpoint and were crossed over to Ropeg; among the risk factors for this failure, the need for more than three bloodletting procedures in the first 6 months emerged as the most important determinant. In conclusion, to improve the effectiveness of Ropeg, we suggest increasing the dose and using it earlier driven by high phlebotomy need in the first 6 months post-diagnosis.

Paediatric porto-sinusoidal vascular disease: Two different clinical phenotypes with subtle histological differences.

BACKGROUND AND AIMS: In paediatrics, porto-sinusoidal vascular disease (PSVD) is relatively unknown and probably underdiagnosed. We aimed to describe clinical phenotypes, histology and outcome of children diagnosed with PSVD. METHODS: Retrospective multicentre study of children diagnosed with PSVD. Diagnosis of PSVD was based on histopathology reports; liver specimens were re-evaluated by two expert liver pathologists. RESULTS: Sixty two children diagnosed with PSVD (M/F = 36/26, median age 6.6 years, range 3.3-10.6), from 7 centres, were included. Thirty-six presented with non-cirrhotic portal hypertension, PH, (PH-PSVD Group = 58%) while 26 had a liver biopsy because of chronic elevation of transaminases without PH (noPH-PSVD Group = 42%). On histology review, the two groups differed for the prevalence of obliterative portal venopathy (more prevalent in PH-PSVD, p = 0.005), and hypervascularised portal tracts (more common in noPH-PSVD, p = 0.039), the other histological changes were equally distributed. At multivariate analysis, platelet count ≤185 000/mm3 was the only independent determinant of PH (p < 0.001). After a median follow-up of 7 years (range 3.0-11.2), in PH-PSVD group 3/36 (8%) required TIPS placement, 5/36 (14%) developed pulmonary vascular complications of PH, and 7/36 (19%) required liver transplantation. In noPH-PSVD none progressed to PH nor had complications. CONCLUSIONS: Paediatric patients with PSVD present with two different clinical phenotypes, one characterised by PH and one by chronic elevation of transaminases without PH. PSVD should be included among the conditions causing isolated hypertransaminasaemia. On histology, the differences between the two groups are subtle. Medium-term outcome is favourable in patients without PH; progression of the disease is observed in those with PH.

Mammographic breast density and survival in women with invasive breast cancer.

PURPOSE: We explored the under-debate association between mammographic breast density (MBD) and survival. METHODS: From the Piedmont Cancer Registry, we identified 693 invasive breast cancer (BC) cases. We analyzed the overall survival in strata of MBD through the Kaplan-Meier method. Using the Cox proportional hazards model, we estimated the hazard ratios (HRs) of death; using the cause-specific hazards regression model, we estimated the HRs of BC-related and other causes of death. Models included term for Breast Imaging-Reporting and Data System (BI-RADS) MBD (categorized as BI-RADS 1 and BI-RADS 2-4) and were adjusted for selected patient and tumour characteristics. RESULTS: There were 102 deaths, of which 49 were from BC. After 5 years, the overall survival was 69% in BI-RADS 1 and 88% in BI-RADS 2-4 (p < 0.01). Compared to BI-RADS 2-4, the HRs of death for BI-RADS 1 were 1.65 (95% CI 1.06-2.58) in the crude model and 1.35 (95% CI 0.84-2.16) in the fully adjusted model. Compared to BI-RADS 2-4, the fully adjusted HRs for BI-RADS 1 were 1.52 (95% CI 0.74-3.13) for BC-related death and 1.83 (95% CI 0.84-4.00) for the other causes of death. CONCLUSION: Higher MBD is one of the strongest independent risk factors for BC, but it seems not to have an unfavorable impact on survival.

Liver transplantation in patients with non-neoplastic portal vein thrombosis: 20 years of experience in a single center.

BACKGROUND: The Yerdel classification is widely used for describing the severity of portal vein thrombosis (PVT) in liver transplant (LT) candidates, but might not accurately predict transplant outcome. METHODS: We retrospectively analyzed data regarding 97 adult patients with PVT who underwent LT, investigating whether the complexity of portal reconstruction could better correlate with transplant outcome than the site and extent of the thrombosis. RESULTS: 79/97 (80%) patients underwent thrombectomy and anatomical anastomosis (TAA), 18/97 (20%) patients underwent non-anatomical physiological reconstructions (non-TAA). PVT Yerdel grade was 1-2 in 72/97 (74%) patients, and 3-4 in 25/97 (26%) patients. Univariate analysis revealed higher 30-day mortality, 90-day mortality, 1-year mortality, and a higher rate of severe early complications in the non-TAA group than in the TAA group (p = .018, .001, .014, .009, respectively). In the model adjusted for PVT Yerdel grade, non-TAA remained independently associated with higher 30-day, 90-day, and 1-year mortality (p = .021, .007, and .015, respectively). The portal vein re-thrombosis and overall patient and graft survival rates were similar. DISCUSSION: In our experience, the complexity of portal reconstruction better correlated with transplant outcome than the Yerdel classification, which did not even appear to be a reliable predictor of the surgical complexity and technique.

Cervical cancer mortality among young women in Latin America and the Caribbean: trend analysis from 1997 to 2030.

BACKGROUND: Cervical cancer continues to show a high burden among young women worldwide, particularly in low- and middle-income countries. Limited data is available describing cervical cancer mortality among young women in Latin America and the Caribbean (LAC). The purpose of this study was to examine the mortality trends of cervical cancer among young women in LAC and predict mortality rates to 2030. METHODS: Deaths from cervical cancer were obtained from the World Health Organization mortality database. Age-standardized mortality rates per 100,000 women-years were estimated in women aged 20-44 years using the world standard population for 16 countries (and territories) in LAC from 1997 to 2017. We estimated the average mortality rates for the last 4 years (2014-2017). Joinpoint regression models were used to identify significant changes in mortality trends. Nordpred method was used for the prediction of the mortality rates to 2030. RESULTS: Between 2014 and 2017, Paraguay and Venezuela had the highest mortality rates of cervical cancer, whereas Puerto Rico had the lowest rates. Overall, most of the LAC countries showed downward trends of cervical cancer mortality over the entire period. Significant decreases were observed in Chile (Average annual percent change [AAPC]: - 2.4%), Colombia (AAPC: - 2.0%), Cuba (AAPC: - 3.6%), El Salvador (AAPC: - 3.1%), Mexico (AAPC: - 3.9%), Nicaragua (AAPC: - 1.7%), Panama (AAPC: - 1.7%), and Peru (AAPC: - 2.2%). In contrast, Brazil (AAPC: + 0.8%) and Paraguay (AAPC: + 3.7%) showed significant upward trends. By 2030, mortality rates are not predicted to further decrease in some LAC countries, including Argentina, Paraguay, and Venezuela. CONCLUSIONS: Mortality trends of cervical cancer among young women have large variability in LAC countries. Cervical cancer screening programs have a high priority for the region. Primary and secondary prevention in the community are necessary to accelerate a reduction of cervical cancer mortality by 2030.

COVID-19 lockdown impact on familial relationships and mental health in a large representative sample of Italian adults.

PURPOSE: Benefits of national-level stay-at-home order imposed in Italy to prevent SARS-CoV-2 transmission need to be carefully weighed against its impact on citizens' health. In a country with a strong familial culture and where welfare relies on households, confinement drastically decreased support provided by elder relatives, which may have resulted in mental health worsening. METHODS: A web-based cross-sectional study (LOST in Italy) was conducted on a representative sample of Italian adults during lockdown (27th of April-3rd of May 2020). We asked 3156 subjects to report on reduced help in housework and childcare from retired parents to assess the impact of confinement on mental health, through validated scales before and during lockdown. RESULTS: Overall, 1484 (47.0%) subjects reported reduced housework help from parents, and 769 (64.0%, of the 1202 subjects with children) diminished babysitting support. Subjects reporting reduced housework help had worsened sleep quality (multivariate odds ratio, OR = 1.74, 95% confidence interval, CI 1.49-2.03) and quantity (OR = 1.50, 95% CI 1.28-1.76), depressive (OR = 1.32, 95% CI 1.14-1.53) and anxiety symptoms (OR = 1.53, 95% CI 1.32-1.78), compared to those reporting unreduced help. Worsening in sleep quality (OR = 2.32, 95% CI 1.76-3.05), and quantity (OR = 1.80, 95% CI 1.36-2.37), depressive (OR = 1.79, 95% CI 1.39-2.31) and anxiety symptoms (OR = 1.90, 95% CI 1.48-2.46) was also associated with reduced babysitting help. Mental health outcomes were worse in subjects with poorer housing and teleworking during lockdown. CONCLUSION: Confinement came along with reduced familial support from parents, negatively impacting household members' mental health. Our findings might inform evidence-based family and welfare policies to promote population health within and beyond pandemic times.

Childhood cancer mortality trends in the Americas and Australasia: An update to 2017.

BACKGROUND: Marked reductions in childhood cancer mortality occurred over the last decades in high-income countries and, to a lesser degree, in middle-income countries. This study aimed to monitor mortality trends in the Americas and Australasia, focusing on areas showing unsatisfactory trends. METHODS: Age-standardized mortality rates per 100,000 children (aged 0-14 years) from 1990 to 2017 (or the last available calendar year) were computed for all neoplasms and 8 leading childhood cancers in countries from the Americas and Australasia, using data from the World Health Organization database. A joinpoint regression was used to identify changes in slope of mortality trends for all neoplasms, leukemia, and neoplasms of the central nervous system (CNS) for major countries. RESULTS: Over the last decades, childhood cancer mortality continued to decrease by approximately 2% to 3% per year in Australasian countries (ie, Japan, Korea, and Australia), by approximately 1.5% to 2% in North America and Chile, and 1% in Argentina. Other Latin American countries did not show any substantial decrease. Leukemia mortality declined in most countries, whereas less favorable trends were registered for CNS neoplasms, particularly in Latin America. Around 2016, death rates from all neoplasms were 4 to 6 per 100,000 boys and 3 to 4 per 100,000 girls in Latin America, and 2 to 3 per 100,000 boys and approximately 2 per 100,000 girls in North America and Australasia. CONCLUSIONS: Childhood cancer mortality trends declined steadily in North America and Australasia, whereas they were less favorable in most Latin American countries. Priority must be given to closing the gap by providing high-quality care for all children with cancer worldwide. LAY SUMMARY: Advances in childhood cancer management have substantially improved the burden of these neoplasms over the past 40 years, particularly in high-income countries. This study aimed to monitor recent trends in America and Australasia using mortality data from the World Health Organization. Trends in childhood cancer mortality continued to decline in high-income countries by approximately 2% to 3% per year in Japan, Korea, and Australia, and 1% to 2% in North America. Only a few Latin American countries showed favorable trends, including Argentina, Chile, and Mexico, whereas other countries with limited resources still lagged behind.

After Action Reviews of COVID-19 response: Case study of a large tertiary care hospital in Italy.

BACKGROUND: After-Action Reviews (AARs) are management tools used to evaluate the response to public health emergencies at the national and subnational level. Aim of this study is to apply available AAR models to assess and critically appraise COVID-19 response of San Raffaele Scientific Institute, a large university hospital in Milan, Italy. METHODS: We designed an AAR based on the key-informant interview format, following the methodology proposed by the 2019 World Health Organization Guidance for AAR. After systematic assessment of the hospital reorganization, we conducted 36 semi-structured interviews to professionals with executive, clinical, technical and administrative roles. We designed an ad-hoc questionnaire exploring four areas: (i) staff management; (ii) logistics and supplies; (iii) COVID-19 diagnosis and clinical management; (iv) communication. RESULTS: Overall, the hospital response was evaluated as effective and sufficiently prompt. Participants stressed the relevance of: (i) strong governance and coordination; (ii) readiness and availability of healthcare personnel; (iii) definition of a model of care based on a multidisciplinary approach. Challenges were reported for communication management and staff training. CONCLUSIONS: This study is one of the first applications of the AAR to the COVID-19 response in hospital settings, which can be successfully adapted or scaled up to other settings in order to implement preparedness strategies for future public health emergencies.

Cancer mortality predictions for 2019 in Latin America.

We estimated mortality figures for 2019 in seven Latin American countries, with focus on breast cancer. We retrieved cancer death certification and population data from the WHO and PAHO databases. We obtained mortality statistics for Argentina, Brazil, Chile, Colombia, Cuba, Mexico and Venezuela for 1970-2015. We predicted current death numbers and age-standardised (world population) mortality rates using joinpoint regression models. Total cancer mortality is predicted to decline in all countries and both sexes, except Argentinian women. Cuba had the highest all cancer rates for 2019, 136.9/100,000 men and 90.4 women, while Mexico showed the lowest ones, 63.8/100,000 men and 61.9 women. Stomach cancer showed favourable trends over the whole period, while colorectal cancer only recently. Lung cancer rates declined in men, while in women they decreased slightly over the most recent years, only. In Cuban women, lung cancer rates overtook breast cancer ones. Breast cancer showed overall favourable trends, but rates are rising in young women. Prostate and uterine cancer had favourable trends. Pancreas, ovary, bladder and leukaemias showed slightly decreasing trends. Between 1990 and 2019, mortality from all neoplasms is predicted to fall by about 18% in Argentina, 26% in Chile, 14% in Colombia, 17% in Mexico and 13% in Venezuela, corresponding to almost 0.5 million avoided cancer deaths. No decline was observed in Brazil and Cuba. Of concern, the persisting high rates of (cervix) uterus cancer, the high lung cancer rates in Cuba, the possible increases in breast cancer in young women, and the lack of overall declines in Brazil, Cuba and Venezuelan men.

Global trends in oral and pharyngeal cancer incidence and mortality.

To provide an up-to-date overview of recent trends in mortality from oral and pharyngeal cancer, we analyzed death certification data for 61 countries worldwide provided by the World Health Organization in 2010-2015, and, for selected most populous countries, over the period 1970-2016. For 12 largest countries, we analyzed incidence derived from Cancer Incidence in Five Continents in 1960-2012 for all oral and pharyngeal cancers and by subsites. In 2015, male age-standardized (world population) death rates per 100,000 were 5.03 in the European Union (EU), 8.33 in the Russian Federation, 2.53 in the United States (USA), and 3.04 in Japan; corresponding rates in women were 1.23, 1.23, 0.82, and 0.76. Male mortality decreased over the last decades in several European countries, with earlier and sharper declines in southern Europe; conversely, mortality was still increasing in a few eastern European countries and the United Kingdom. Mortality in men also decreased in Argentina, Australia, and Hong Kong, while it leveled off over more recent calendar years in Brazil, Japan, Mexico, the Republic of Korea, as well as in Australia and the USA. Female mortality slightly rose in various European countries. Overall incidence trends in the largest countries were broadly consistent with mortality ones, but oropharyngeal cancer incidence rose in many countries. Changes in tobacco and alcohol exposure in men over the last decades likely explain the favorable trends in oral and pharyngeal cancer mortality and incidence observed in selected countries worldwide, while increased human papillomavirus infection is likely responsible for the rise in oropharyngeal cancer incidence.

The impact of selected risk factors among breast cancer molecular subtypes: a case-only study.

PURPOSE: Breast cancer (BC) risk factors have been differentially associated with BC subtypes, but quantification is still undefined. Therefore, we compared selected risk factors with BC subtypes, using a case-case approach. METHODS: We retrieved 1321 invasive female BCs from the Piedmont Cancer Registry. Through record linkage of clinical records, we obtained data on estrogen (Er) and progesterone (Pr) receptors, Ki67 and HER2+ status, BC family history, breast imaging reporting and data system (BI-RADS) density, reproductive risk factors and education. We defined BC subtypes as follows : luminal A (Er+ and/or Pr+ , HER2- , low Ki67), luminal BH- (Er+ and/or Pr + , HER2- , Ki67 high), luminal BH+ (Er+ and/or Pr + , HER2+), HER2+ (Er - , Pr - , HER2+), ) and triple negative (Er - , Pr - , HER2-). Using a multinomial regression model, we estimated the odds ratios (ORs) for selected BC risk factors considering luminal A as reference. RESULTS: For triple negative, the OR for BC family history was 1.83 (95% confidence interval (CI) 1.13-2.97). Compared to BI-RADS 1, for triple negative, the OR for BI-RADS 2 was 0.56 (95% CI 0.27-1.14) and for BI-RADS 3-4 was 0.37 (95% CI 0.15-0.88); for luminal BH +, the OR for BI-RADS 2 was 2.36 (95% CI 1.08-5.11). For triple negative, the OR for high education was 1.78 (95% CI 1.03-3.07), and for late menarche, the OR was 1.69 (95% CI 1.02-2.81). For luminal BH + , the OR for parous women was 0.56 (95% CI 0.34-0.92). CONCLUSIONS: This study supported BC etiologic heterogeneity across subtypes, particularly for triple negative.

Breast cancer mortality trends in Peruvian women.

BACKGROUND: Breast cancer (BC) is the most common malignancy in Latin American women, but with a wide variability with respect to their mortality. This study aims to estimate the mortality rates from BC in Peruvian women and to assess mortality trends over 15 years. METHODS: We calculated BC age-standardized mortality rate (ASMR) per 100,000 women-years using the world standard SEGI population. We estimated joinpoint regression models for BC in Peru and its geographical areas. The spatial analysis was performed using the Moran's I statistic. RESULTS: In a 15-year period, Peru had a mortality rate of 9.97 per 100,000 women-years. The coastal region had the highest mortality rate (12.15 per 100,000 women-years), followed by the highlands region (4.71 per 100,000 women-years). In 2003, the highest ASMR for BC were in the provinces of Lima, Arequipa, and La Libertad (above 8.0 per 100,000 women-years), whereas in 2017, the highest ASMR were in Tumbes, Callao, and Moquegua (above 13.0 per women-years). The mortality trend for BC has been declining in the coastal region since 2005 (APC = - 1.35, p < 0.05), whereas the highlands region experienced an upward trend throughout the study period (APC = 4.26, p < 0.05). The rainforest region had a stable trend. Spatial analysis showed a Local Indicator of Spatial Association of 0.26 (p < 0.05). CONCLUSION: We found regional differences in the mortality trends over 15 years. Although the coastal region experienced a downward trend, the highlands had an upward mortality trend in the entire study period. It is necessary to implement tailored public health interventions to reduce BC mortality in Peru.

Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: Intrahepatic (ICC) and extrahepatic cholangiocarcinoma (ECC) have rarely been studied individually, probably due to difficulties in their diagnosis and certification. Mortality trends from these 2 neoplasms have been inconsistent over the last decades. The aim of this study was to analyze worldwide trends in mortality from ICC and ECC in selected countries. METHODS: We extracted death certification data for ICC and ECC, and population estimates from the World Health Organization and Pan American Health Organization databases for 32 selected countries from Europe, the Americas, and Australasia from 1995 to 2016. We computed age-standardized (world population) mortality rates from ICC and ECC, and performed joinpoint regression analysis. RESULTS: Mortality rates from ICC increased in all countries considered, with a levelling off over recent years in Germany (women), Italy (men), Argentina (men), the USA (men), Hong Kong (men), and Japan (both sexes). The highest rates in 2010-2014 (1.5-2.5/100,000 in men and 1.2-1.7/100,000 in women) were registered in Hong Kong, France, Austria, Spain, the UK, and Australia. The lowest rates (0.2-0.6/100,000 in both sexes) were registered in Latin American and eastern European countries. Mortality from ECC decreased in most of the countries considered, with rates below 1/100,000 in both sexes between 2010 and 2014, with the only exception being Japan (2.8/100,000 in men and 1.4/100,000 in women). CONCLUSIONS: Increasing mortality from ICC was observed globally, due to trends in risk factors and possibly, in part, due to better disease classification. Mortality from ECC levelled off or decreased, most likely following the increased use of laparoscopic cholecystectomy. LAY SUMMARY: Biliary tract cancers include intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC), however there are some differences in their risk factors. Consequently, the distinction between ICC and ECC is important. Over the last few decades, mortality from ICC has tended to rise in several areas of the world, following the increased prevalence of its major risk factors. In contrast, mortality from ECC tended to decrease in most countries, following the increased use of laparoscopic cholecystectomy.

Management and Survival of Pleural Mesothelioma: A Record Linkage Study.

BACKGROUND: Pleural mesothelioma (PM) is a rare, highly lethal tumor. A definite consensus on its management has yet to be established. OBJECTIVES: To assess management, overall survival (OS), and their predictors in a cohort of patients from Lombardy, the largest Italian region (about 10 million inhabitants). METHODS: Through a record linkage between Lombardy health care administrative databases, we identified patients diagnosed with PM in 2006-2011 without history of cancer, evaluating their management. OS from PM diagnosis was estimated using the Kaplan-Meier method. Predictors of OS and of treatment were assessed using Cox regression models with time-dependent covariates when appropriate. RESULTS: Out of 1,326 patients, 754 (56.9%) received treatment for PM: 205 (15.5%) underwent surgery, and 696 (52.5%) used chemotherapy. Surgery was spread across several hospitals, and most patients diagnosed in nonspecialized centers (70%) underwent surgery in the same centers. Age at diagnosis was a strong inverse determinant of surgery. Determinants of receiving chemotherapy were younger age, a more recent first diagnosis, and first diagnosis in a specialized center. OS was 45.4% at 1 year, 24.8% at 2 years, and 9.6% at 5 years (median 11 months). OS decreased with age, and was higher for those who underwent surgery, but not for those treated with chemotherapy. CONCLUSIONS: Management of PM varied widely in clinical practice, and significant predictors of treatment were younger age and recent diagnosis, though a high proportion of patients were not treated. Patients were treated in various hospitals, indicating the importance of concentrating serious rare neoplasms in Comprehensive Cancer Centers (as recognized by the Italian Health Ministry).

Global trends in nasopharyngeal cancer mortality since 1970 and predictions for 2020: Focus on low-risk areas.

Nasopharyngeal cancer (NPC) mortality shows great disparity between endemic high risk areas, where non-keratinizing carcinoma (NKC) histology is prevalent, and non-endemic low risk regions, where the keratinizing squamous cell carcinoma (KSCC) type is more frequent. We used the World Health Organization database to calculate NPC mortality trends from 1970 to 2014 in several countries worldwide. For the European Union (EU), the United States (US) and Japan, we also predicted trends to 2020. In 2012, the highest age-standardized (world standard) rates were in Hong Kong (4.51/100,000 men and 1.15/100,000 women), followed by selected Eastern European countries. The lowest rates were in Northern Europe and Latin America. EU rates were 0.27/100,000 men and 0.09/100,000 women, US rates were 0.20/100,000 men and 0.08/100,000 women and Japanese rates were 0.16/100,000 men and 0.04/100,000 women. NPC mortality trends were favourable for several countries. The decline was -15% in men and -5% in women between 2002 and 2012 in the EU, -12% in men and -9% in women in the US and about -30% in both sexes in Hong Kong and Japan. The favourable patterns in Europe and the United States are predicted to continue. Changes in salted fish and preserved food consumption account for the fall in NKC. Smoking and alcohol prevalence disparities between sexes and geographic areas may explain the different rates and trends observed for KSCC and partially for NKC. Dietary patterns, as well as improvement in management of the disease, may partly account for the observed trends, too.

Global trends and predictions in hepatocellular carcinoma mortality.

BACKGROUND & AIMS: Trends in hepatocellular carcinoma (HCC) mortality rates have increased over recent decades in most countries. It is also the third cause of cancer death worldwide. The aim of this study is to update global trends in HCC mortality to 2014, and predict trends in rates in the EU, USA and Japan to 2020. METHODS: Death certification data for HCC over the 1990-2014 period from the World Health Organization database were analyzed. Sixteen European, five American countries, and six other countries worldwide were included, as well as the EU as a whole. RESULTS: In European men, mortality rates were stable during the last decade (3.5/100,000). HCC mortality increased in Northern and Central Europe, and decreased in Southern Europe. In the USA, HCC mortality increased by 35% between 2002 and 2012, reaching 3.1/100,000 men in 2012; it is predicted to remain stable to 2020. Reduced mortality rates were observed in East Asia, although they remained around 10-24/100,000 men. In Japan, HCC mortality is predicted to decrease (5.4/100,000 men in 2020). Trends were favorable in the young, but unfavorable in middle aged, except in East Asia. Mortality rates were 3- to 5-fold lower in women than men in most regions, but trends were similar. CONCLUSIONS: Control of hepatitis B (HBV) and hepatitis C virus (HCV) infections has contributed to the decrease in HCC-related mortality in East Asia and Southern Europe. Unfavorable trends in other regions can be attributed to HCV (and HBV) epidemics in the 1960s and 1980s, alcohol consumption, increased overweight/obesity, and diabetes. Better management of cirrhosis, HCC diagnosis and treatment are also influencing the mortality trends worldwide. LAY SUMMARY: Mortality rates due to HCC have increased in many countries over recent decades. In this study, we updated worldwide mortality trends for HCC from 1990 to 2014, and predicted trends for some countries to 2020. We observed unfavorable trends in Northern and Central Europe, North and Latin America. East Asia showed an improvement, however mortality rates in this region were 2- to 5-fold higher than in most European countries and the Americas. Steady declines to 2020 are predicted for East Asia but not for Europe and the Americas.

Global Trends in Pancreatic Cancer Mortality From 1980 Through 2013 and Predictions for 2017.

BACKGROUND & AIMS: Pancreatic cancer is a leading cause of cancer mortality, and its mortality has not decreased in recent years. We sought to determine global trends in pancreatic cancer mortality. METHODS: We derived data on deaths from pancreatic cancer from the World Health Organization database for 59 countries from 1980 through 2013. Age-standardized mortalities were computed for persons of all ages and for persons 35-64 years old; for selected countries, they were computed for persons 25-49 years old. Joinpoint regression models were used to identify significant changes in mortality. For selected larger countries, we predicted number of deaths and mortality for 2017. RESULTS: Between 1980 and 2013, overall pancreatic cancer mortality in men increased in the European Union (EU) as well as in Southern and Eastern Europe, Brazil, Japan, and Republic of Korea. Overall pancreatic cancer mortality decreased in most Northern European countries, Australia, Canada, Mexico, and the United States (US). In women, mortality increased in the EU, Brazil, US, Japan, and Republic of Korea but decreased in Canada and Mexico. In 2012, Eastern Europe and Japan had the highest pancreatic cancer mortality for both sexes. In men 25-49 years old, mortality decreased in the EU, US, Japan, and most large European countries. On the basis of our data, we predict overall pancreatic cancer mortality in 2017 to level off in men in the EU and US but increase in Japan. In women, mortality will continue to increase in most countries except the US; the greatest increase is predicted to occur in Japan. CONCLUSIONS: Mortality from pancreatic cancer has not decreased as it has for other cancers in recent years. A notable exception is a decrease in mortality in men 25-49 years old, which could indicate a reversal in the current increasing global trends.

Prognostic role of gait speed in worsening heart failure.

BACKGROUND: Worsening Heart Failure (WHF) is associated with adverse prognosis. Identifying novel prognostic markers in WHF is crucial. Gait speed (GS), a validated frailty index, is an easily obtainable parameter that may aid in reclassifying the risk of HF patients. We assessed the independent prognostic role of GS in WHF patients. METHODS: We studied 171 patients with chronic HF with worsening congestion symptoms and inadequate response to standard therapies, requiring intravenous diuretic treatment. The primary outcome was a composite of all-cause mortality or HF hospitalization. We assessed the association and the incremental value of GS, as compared to other clinical confounders, with the primary outcome. RESULTS: The mean age was 76±11 years, 66 % were male, median BNP was 481 pg/ml, and median ejection fraction was 40 %. Over a median follow-up of 11.3 months, 71 events occurred. Lower GS was significantly associated with a higher risk of events (HR of 4.03, 95 % CI 2.25-7.21), along with neutrophil to lymphocyte ratio, BNP, QRS duration, natremia, and previous myocardial infarction. When added to the MAGGIC risk score and the other significant confounders identified, GS significantly enhanced the model risk prediction (Harrell's C-index 0.75 vs 0.71, p < 0.001). At Classification And Regression Tree analysis, GS≤0.8 m/s was the first parameter to be considered to risk stratify the population. CONCLUSIONS: GS, an easily obtainable marker of frailty, may contribute to improve the risk stratification of patients with WHF.

Clonal Hematopoiesis in Myeloproliferative Neoplasms Confers a Predisposition to both Thrombosis and Cancer.

PURPOSE OF REVIEW: This review focuses on vascular complications associated with chronic myeloproliferative neoplasms (MPN) and more specifically aims to discuss the clinical and biological evidence supporting the existence of a link between clonal hematopoiesis, cardiovascular events (CVE), and solid cancer (SC). RECENT FINDINGS: The MPN natural history is driven by uncontrolled clonal myeloproliferation sustained by acquired somatic mutations in driver (JAK2, CALR, and MPL) and non-driver genes, involving epigenetic (e.g., TET2, DNMT3A) regulators, chromatin regulator genes (e.g., ASXL1, EZH2), and splicing machinery genes (e.g., SF3B1). The genomic alterations and additional thrombosis acquired risk factors are determinants for CVE. There is evidence that clonal hematopoiesis can elicit a chronic and systemic inflammation status that acts as driving force for the development of thrombosis, MPN evolution, and second cancer (SC). This notion may explain the mechanism that links arterial thrombosis in MPN patients and subsequent solid tumors. In the last decade, clonal hematopoiesis of indeterminate potential (CHIP) has been detected in the general population particularly in the elderly and initially found in myocardial infarction and stroke, rising the hypothesis that the inflammatory status CHIP-associated could confer predisposition to both cardiovascular diseases and cancer. In summary, clonal hematopoiesis in MPN and CHIP confer a predisposition to cardiovascular events and cancer through chronic and systemic inflammation. This acquisition could open new avenues for antithrombotic therapy both in MPNs and in general population by targeting both clonal hematopoiesis and inflammation.