The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Boosting biopesticide potential of Trichoderma harzianum for controlling the downy mildew and improving the growth and the productivity of King Ruby seedless grape

Abstract Background Plasmopara viticola, the causal agent of grape downy mildew, is one of the most serious grape diseases. Application of Trichoderma harzianum grown on different potato dextrose supplemented broth media using some chemical inducers (TSDCIS), i.e., thiamine (T2), a mixture of micronutrients (T3) and potassium tartrate (T4), compared to Trichoderma without amendment (T1), was conducted under field conditions to evaluate the potential of T. harzianum against grape downy mildew, improving the growth, as well as the yield quality, and quantity. Results Foliar application of all TSDCIS significantly reduced the disease severity and increased the phenolic content, peroxidase, polyphenol oxidase enzyme activity, growth parameters, and yield parameters. Trichoderma growing on medium supplemented with potassium tartrate (T4) achieved the most significant reduction in the disease severity (78.9, 81.8%) than the control treatment in two growing seasons, respectively. In contrast, it decreased H2O2 content, lipid peroxidation, and cellular electrolyte leakage. Scanning electron microscopy observations revealed that the number of opened stomata, average stomatal area, and stomatal pore area decreased significantly in response to T4 treatment. Conclusions It can be concluded that using Trichoderma growing on medium supplemented with potassium tartrate (T4) to biosafety control the downy mildew disease of grape and improve its growth, yield, and fruit quality is recommended

Assessing different barley growth habits under Egyptian conditions for enhancing resilience to climate change

41 Pags.- 14 Tabls.- 5 Figs. The definitive version is available at: https://www.sciencedirect.com/science/journal/03784290Climate change poses challenges to agricultural production in general and to plant breeders in particular. Adaptation of cereals to the new conditions and increasingly variable situations arising from this process is essential to reduce risks and limit potential threats associated with climate hazards. This study presents the first attempt to assess the response and resilience of barley genotypes, with different growth habits across Egypt. For this purpose, eight field trials were conducted from 2013 to 2016 at three experimental sites with different winter climate configurations. The trials were sown at the end of November, following recommendations for the region. Fourteen barley genotypes were evaluated, comprising seven commercial Egyptian cultivars and seven European genotypes. The European genotypes were selected from successful cultivars from Spain, encompassing a range of growth types: two spring, three intermediate and two winter types. The cultivars were genotyped for six major adaptation genes, Vrn-H1-2-3, Ppd-H1-2 and HvCEN. One interesting finding is that, while the Egyptian cultivars were assumed to be of spring growth type, our results demonstrate that two cultivars, namely Giza123 and Giza126, are actually intermediate types (needing just a short period of vernalization). They contain the winter allele at Vrn-H2 together with Vrn-H1-4, the same as the European genotypes Cierzo and Orria, they also have an active allele at PpdH2, such as Hispanic. Overall, these four genotypes showed very good performance in all trials with low genotype-by-environment interaction. Moreover, a foreign late spring genotype (Pewter) was highly productive and a winter genotype (Hispanic) flowered as early as some intermediate and spring genotypes with a yield similar to genotypes currently grown in Egypt. A possible explanation for this surprising occurrence, the influence of an active allele at PpdH2 in winter cultivars, is discussed. In relation to low temperature, a high frequency of cold nights during wintertime was observed at all experimental sites, which seemed sufficient to promote timely flowering for intermediate genotypes, although this was inadequate for promoting flowering and achieving good productivity in strictly winter genotypes (e.g. Barberousse). Our findings also highlight the potential of exotic germplasm for breeding better and more resilient cultivars for autumn and for achieving good yield levels in regions with warm winters like Egypt. The results also provide insights into the usefulness of genetic variation in growth habit for breeders seeking adaptation to climate change conditions.AMC and EI acknowledge funding from Spanish MINECO, grants AGL2013-48756-R and AGL2016-80967-R.Peer reviewe

Field responses of barley genotypes across a salinity gradient in an arid Mediterranean environment

11 Pags.- 7 Figs.- 4 Tabls.Salinity is one of the most widespread abiotic stresses affecting crop growth and productivity, particularly when soil and irrigation water are salty. Field experiments were performed in an arid Mediterranean climate to investigate agronomic responses of twenty-one diverse barley genotypes to naturally occurring salinity. Three saline fields (7.72 dS/m) were irrigated with well water of three incremental salinity levels, low (5.25 dS/m), intermediate (8.35 dS/m), and high (11.12 dS/m). The results revealed considerable genotypic variability at the three salinity levels and significant genotype by salinity interaction that could be traced to specific yield components. Increasing salinity level decreased performance of all agronomic traits, but with different patterns, with yield components determined earlier being more affected than traits determined later. Days to heading exhibited a strong and negative relationship with grain yield across all salinity levels, while 1000-grain weight demonstrated the highest association with grain yield, followed by number of grains per spike, plant height, and harvest index, consistently at the three salinity levels. The genotypes were classified based on their yield indices at the three salinity levels into six groups varying from highly salt-tolerant (group A) to highly salt-sensitive genotypes (group F). Genotype-by-salinity interaction was studied based on rankings of performance across salinity levels. Close examination of yield component trends across levels allowed the identification of genotypes with different behaviors, indicating the presence of variation in potentially different mechanisms of response to salinity. This diversity of responses could be used in breeding to improve tolerance over the whole crop cycle, from plant establishment and tillering to grain filling.Peer reviewe

Assessment of Eight Faba Bean (<i>Vicia faba</i> L.) Cultivars for Drought Stress Tolerance through Molecular, Morphological, and Physiochemical Parameters

Determining and improving drought-tolerant cultivars is a major goal of plant breeding to face climate change. The productivity of faba bean in Egypt is affected by abiotic stresses, especially drought stress. This study evaluated eight Egyptian faba bean cultivars for drought tolerance under three soil water regimes consisting of well-watered (100% field capacity), moderate drought stress (50% field capacity), and severe drought stress (25% field capacity) regimes in pots under greenhouse conditions using biochemical, physiochemical, and molecular parameters. The cultivars Nubariya 1, Nubariya 3, and Giza 716 showed the highest proline content values under 50% field capacity conditions, with 4.94, 4.39, and 4.26 mmol/g fresh weights, respectively. On the other hand, the cultivars Sakha 1, Sakha 4, Nubariya 1, and Nubariya 3 exhibited the highest proline contents (7.8, 7.53, 6.17, and 6.25, respectively) under 25% field capacity treatment. The molecular profiling was conducted using SCoT and SRAP approaches. Fresh leaves were utilized to extract the DNA, and ten primers for SRAP and six for SCoT were used in the PCR procedures. SCoT and SRAP-PCR generated 72 loci, of which, 55 were polymorphic, and 17 were monomorphic. SCoT and SRAP each had 48 and 24 total loci, respectively. The average polymorphism (%) values achieved via SCoT and SRAP were 70.93% and 80%, respectively. Based on the molecular profiles, the cluster analysis identified three clusters. The first cluster comprised Giza 716 cultivars; the second cluster included Sakha 1, Sakha 3, Sakha 4, and Akba 3300 cultivars; the third cluster comprised two cultivars Nubariya 1 and Nubariya3. According to the study’s findings, Sakha 1, Sakha 4, Nubariya 1, and Nubariya 3 are remarkable parents for developing drought-tolerant faba bean genotypes. Additionally, this study concluded that SRAP and SCoT markers recreated trustworthy banding profiles to evaluate the genetic polymorphism among faba bean cultivars, which are regarded as the cornerstone for genetic improvements in crops

Acute kidney disease beyond day 7 after major surgery: a secondary analysis of the EPIS-AKI trial

Purpose: Acute kidney disease (AKD) is a significant health care burden worldwide. However, little is known about this complication after major surgery. Methods: We conducted an international prospective, observational, multi-center study among patients undergoing major surgery. The primary study endpoint was the incidence of AKD (defined as new onset of estimated glomerular filtration rate (eCFR) &lt; 60&nbsp;ml/min/1.73&nbsp;m2 present on day 7 or later) among survivors. Secondary endpoints included the relationship between early postoperative acute kidney injury (AKI) (within 72&nbsp;h after major surgery) and subsequent AKD, the identification of risk factors for AKD, and the rate of chronic kidney disease (CKD) progression in patients with pre-existing CKD. Results: We studied 9510 patients without pre-existing CKD. Of these, 940 (9.9%) developed AKD after 7&nbsp;days of whom 34.1% experiencing an episode of early postoperative-AKI. Rates of AKD after 7&nbsp;days significantly increased with the severity (19.1% Kidney Disease Improving Global Outcomes [KDIGO] 1, 24.5% KDIGO2, 34.3% KDIGO3; P &lt; 0.001) and duration (15.5% transient vs 38.3% persistent AKI; P &lt; 0.001) of early postoperative-AKI. Independent risk factors for AKD included early postoperative-AKI, exposure to perioperative nephrotoxic agents, and postoperative pneumonia. Early postoperative-AKI carried an independent odds ratio for AKD of 2.64 (95% confidence interval [CI] 2.21-3.15). Of 663 patients with pre-existing CKD, 42 (6.3%) had worsening CKD at day 90. In patients with CKD and an episode of early AKI, CKD progression occurred in 11.6%. Conclusion: One in ten major surgery patients developed AKD beyond 7&nbsp;days after surgery, in most cases without an episode of early postoperative-AKI. However, early postoperative-AKI severity and duration were associated with an increased rate of AKD and early postoperative-AKI was strongly associated with AKD independent of all other potential risk factors

Epidemiology of surgery associated acute kidney injury (EPIS-AKI): a prospective international observational multi-center clinical study

Purpose: The incidence, patient features, risk factors and outcomes of surgery-associated postoperative acute kidney injury (PO-AKI) across different countries and health care systems is unclear. Methods: We conducted an international prospective, observational, multi-center study in 30 countries in patients undergoing major surgery (&gt; 2-h duration and postoperative intensive care unit (ICU) or high dependency unit admission). The primary endpoint was the occurrence of PO-AKI within 72&nbsp;h of surgery defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary endpoints included PO-AKI severity and duration, use of renal replacement therapy (RRT), mortality, and ICU and hospital length of stay. Results: We studied 10,568 patients and 1945 (18.4%) developed PO-AKI (1236 (63.5%) KDIGO stage 1500 (25.7%) KDIGO stage 2209 (10.7%) KDIGO stage 3). In 33.8% PO-AKI was persistent, and 170/1945 (8.7%) of patients with PO-AKI received RRT in the ICU. Patients with PO-AKI had greater ICU (6.3% vs. 0.7%) and hospital (8.6% vs. 1.4%) mortality, and longer ICU (median 2 (Q1-Q3, 1-3) days vs. 3 (Q1-Q3, 1-6) days) and hospital length of stay (median 14 (Q1-Q3, 9-24) days vs. 10 (Q1-Q3, 7-17) days). Risk factors for PO-AKI included older age, comorbidities (hypertension, diabetes, chronic kidney disease), type, duration and urgency of surgery as well as intraoperative vasopressors, and aminoglycosides administration. Conclusion: In a comprehensive multinational study, approximately one in five patients develop PO-AKI after major surgery. Increasing severity of PO-AKI is associated with a progressive increase in adverse outcomes. Our findings indicate that PO-AKI represents a significant burden for health care worldwide