Global epidemiology of early-onset upper gastrointestinal cancer: trend from the Global Burden of Disease Study 2019.

BACKGROUND AND AIM: In recent years, there has been a growing incidence of gastrointestinal cancer in young individuals. Despite its significant morbidity and mortality, research on upper gastrointestinal (UGI) cancer in young populations has been relatively limited. Therefore, studies on the epidemiological changes of this cancer are needed. METHODS: Using data from the Global Burden of Disease Study 2019, we examined the incidence, death, and disability-adjusted life years (DALYs) from UGI cancers in the young, namely, early-onset esophageal cancer (EOEC) and early-onset gastric cancer (EOGC). These results were stratified by sex, geographical region, country, and sociodemographic index. RESULTS: There was a total of 185 140 cases, 120 289 deaths, and 5.70 million DALYs attributable to early-onset UGI cancers globally. From 2010 to 2019, the global incidence, death, and DALYs rates of early-onset UGI cancers decreased. In contrast, the incidence rates increased in both EOEC (+1.15%) and EOGC (+0.21%) in the Eastern Mediterranean region. CONCLUSIONS: Over the past decade, the burden of UGI cancer in the young has decreased. However, it has increased in the Eastern Mediterranean region. Further research to elucidate the attributable risk factors in this population is warranted.

Donepezil ameliorates gut barrier disruption in doxorubicin-treated rats.

An impact of donepezil against doxorubicin-induced gut barrier disruption and gut dysbiosis has never been investigated. Twenty-four male Wistar rats were divided into three groups. Each group was treated with either vehicle as a control, doxorubicin, or doxorubicin-cotreated with donepezil. Heart rate variability was assessed to reflect the impact of doxorubicin and donepezil. Then, animals were euthanized, and the ileum and its contents were collected in each case to investigate the gut barrier and gut microbiota, respectively. The microbiota-derived endotoxin, trimethylamine N-oxide (TMAO), and short-chain fatty acids (SCFAs) in the serum were determined. An increase in the sympathetic tone, endotoxins, and TMAO levels with disruption of the gut barrier and a decrease in SCFAs levels were observed in doxorubicin-treated rats. Gut microbiota of doxorubicin-treated rats was significantly different from that of the control group. Donepezil treatment significantly decreased the sympathetic tone, restored the gut barrier, and reduced endotoxin and TMAO levels in doxorubicin-treated rats. Nonetheless, donepezil administration did not alter the gut microbiota profile and levels of SCFAs in doxorubicin-treated rats. Doxorubicin impaired the autonomic balance and the gut barrier, and induced gut dysbiosis, resulting in gut toxicity. Donepezil partially improved the doxorubicin-induced gut toxicity through balancing the autonomic disturbance.

The Global Burden of Early-Onset Pancreatic Cancer and Its Risk Factors: A Perspective From Global Burden of Disease Study 2019.

OBJECTIVES: Despite evidence of increased incidence of early-onset pancreatic cancer (EOPC), defined as pancreatic cancer diagnosed in patients below 50 years old, and its risk factors in the Western region, global epidemiological data addressing this issue is still lacking. MATERIALS AND METHODS: Utilizing data from the Global Burden of Disease Study 2019, we aimed to conduct a comprehensive analysis of the incidence, deaths, and disability-adjusted life years (DALYs) associated with EOPC and its risk factors, including smoking, obesity, and diabetes. The analysis examined the annual percentage change (APC) over the period. RESULTS: In 2019, the incidence of EOPC surpassed 35,000 cases worldwide. This burden of EOPC tends to be more prevalent in males, as well as in Europe and high SDI countries. However, there is a noticeable upward trend in the burden of EOPC in the Eastern Mediterranean. While there is a global decline in EOPC mortality attributed to smoking (APC -0.33%), there is a concerning increase in mortality associated with diabetes (APC +2.84%) and obesity (APC +2.12%). CONCLUSIONS: The burden of EOPC has been increasing. The mortality is rising mainly from metabolic factors. There is an urgent need for national policy development for reducing the burden of this disease.

Global and regional burden of alcohol-associated liver disease and alcohol use disorder in the elderly.

Background & Aims: Alcohol-associated liver diseases (ALDs) and alcohol use disorder (AUD) pose a global health risk. AUD is underrecognized in the elderly, and the burden of AUD complications, including ALD, may increase with aging populations and rising alcohol intake. However, there is a lack of epidemiological evidence on AUD and ALD in the elderly. Methods: Using the Global Burden of Disease Study 2019, we analyzed the prevalence, mortality, disability-adjusted life years (DALYs), age-standardized rates (ASRs), and temporal change from 2000 to 2019 of ALD and AUD in the overall population and the elderly (65-89 years). The findings were categorized by sex, region, nation, and sociodemographic index. Results: The prevalence rates of ALD in the elderly were higher than those in adolescents and young adults, whereas AUD levels were lower than those in adolescents and young adults. In 2019, there were 9.39 million cases (8.69% of cases in the overall population) of AUD, 3.23 million cases (21.8% of cases in the overall population) of alcohol-associated cirrhosis, and 68,468 cases (51.27% of cases in the overall population) of liver cancer from alcohol among the elderly. ASRs of the prevalence of ALD and AUD in the elderly increased in most regions; on the contrary, ASRs of death and DALYs decreased in most regions. Nevertheless, ASRs of death and DALYs from liver cancer from alcohol increased in many areas. Conclusions: Our findings highlighted the increased prevalence of ALD in the elderly, with a burden of AUD comparable with that in the overall population. Public health strategies on ALD and AUD targeting the elderly are urgently needed. Impact and implications: The burden of alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) is increasing. Advances in healthcare and education have resulted in a remarkable spike in life expectancy and a consequential population aging. Nevertheless, little is known about the epidemiology of ALD and AUD in the elderly. Our study indicates the increasing burden of ALD and AUD in the elderly population, necessitating early detection, intervention, and tailored care to the unique needs and complexities faced by older individuals grappling with these conditions.

What Is New in Metabolic Dysfunction-Associated Steatotic Liver Disease in Lean Individuals: From Bench to Bedside.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of the world's adult population. While it is associated with obesity and metabolic syndrome, emerging evidence has shown that a substantial number of MASLD patients have a normal body mass index ("lean individuals with MASLD"). In this article, we provide an overview of the definition, epidemiology, pathogenesis, and clinical outcomes associated with lean individuals with MASLD and updates on current management.

From Shadows to Spotlight: Exploring the Escalating Burden of Alcohol-Associated Liver Disease and Alcohol Use Disorder in Young Women.

INTRODUCTION: The burden of alcohol-related complications is considerable, particularly alcohol-associated liver disease and alcohol use disorder (AUD). However, there are deficiencies in comprehensive epidemiological research focusing on these issues, especially among young women who display higher susceptibility to such complications compared with their male counterparts. We thus aimed to determine the global burden of these conditions in this vulnerable group. METHODS: Leveraging data from the Global Burden of Disease Study 2019, we analyzed the prevalence, mortality, and disability-adjusted life years of alcohol-associated cirrhosis (AC), liver cancer from alcohol, and AUD in young women. The findings were categorized by region, nation, and sociodemographic index. RESULTS: The highest age-standardized prevalence rates were observed in AUD (895.96 [95% uncertainty interval (UI) 722.6-1,103.58]), followed by AC (65.33 [95% UI 48.37-86.49]) and liver cancer from alcohol (0.13 [95% UI 0.09-0.19]) per 100,000 people. The highest age-standardized mortality rates were observed in AC (0.75 [95% UI 0.55-0.97]), followed by AUD (0.48 [95% UI 0.43-0.53]) and liver cancer from alcohol (0.06 [95% UI 0.04-0.09]). The highest burdens of AC and AUD were observed in Central Europe, whereas the high-income Asia Pacific had the highest burden of liver cancer from alcohol. DISCUSSION: Throughout the past decade, the trend of AUD varied among regions while the impact of alcohol-associated liver disease has increased, requiring urgent public health strategy to mitigate these complications, particularly in female patients in Europe and the Asia-Pacific region.

Global Epidemiology and Burden of Elderly-Onset Inflammatory Bowel Disease: A Decade in Review.

Inflammatory bowel disease (IBD), once thought to impact younger individuals, now manifests in approximately 10% of patients over 65, characterized by a heightened vulnerability to complications and greater diagnostic intricacies than conventional cases. However, comprehensive global epidemiological data regarding elderly-onset IBD are currently insufficient. Our study addresses this critical gap by analyzing trends in elderly-onset IBD over a decade, encompassing the estimation of annual frequencies and age-standardized rates of elderly-onset IBD burden for both genders, stratifying the data by geographical and sociodemographic factors. Our research highlights a notable increase in the proportion of elderly-onset IBD, constituting around 13% of all IBD cases. We observed a rising incidence in males, contrasted by a decreasing trend in females. The highest surge in incidence rates was seen in the Western Pacific region in both genders, but the highest burden was observed in America. Countries with high sociodemographic index (SDI) carried the greatest burden of elderly-onset IBD, while countries with low SDI had the least. The mortality and disability-adjusted life years (DALYs) rates trend downward in most regions. This study underscores an increasing incidence and proportion of IBD, particularly in elderly-onset IBD, particularly in males. While mortality and DALYs are decreasing in most regions, the overall burden remains highest in America and high-SDI countries. Effective public health interventions and comprehensive studies are required to tackle this mounting burden.

Combined caloric restriction and exercise provides greater metabolic and neurocognitive benefits than either as a monotherapy in obesity with or without estrogen deprivation.

Neurodegeneration, as indicated by brain dysfunction and cognitive decline, is one of the complications associated with obesity and estrogen deprivation. Calorie restriction and exercise regimes improved brain function in neurodegenerative diseases. However, the comparative effects of a combination of calorie restriction with exercise, calorie restriction, and an exercise regime alone on brain/cognitive function in obesity with or without estrogen deprivation have not been investigated. Sixty female rats were fed a normal diet (ND) or a high-fat diet (HFD) for 27 weeks. At week 13, the ND-fed rats underwent a sham operation with sedentary lifestyle, HFD-fed rats were divided into two groups: each having either a sham operation (HFS) or ovariectomy (HFO). At week 20, HFD-fed rats in each group were divided into four subgroups undergoing either a sedentary lifestyle, calorie restriction, exercise regime or a combination of calorie restriction and exercise for 7 weeks. Insulin resistance, cognitive decline and hippocampal pathologies were found in both HFS and HFO rats. HFO rats had higher levels of insulin resistance and hippocampal reactive oxygen species levels than HFS rats. Calorie restriction decreased metabolic disturbance and hippocampal oxidative stress but failed to attenuate cognitive decline in HFS and HFO rats. Exercise attenuated metabolic/hippocampal dysfunctions, resulting in improved cognition only in HFS rats. Combined therapies restored brain function, and cognitive function in HFS and HFO rats. Therefore, a combination of calorie restriction with exercise is probably the greatest lifestyle modification to diminish the brain pathologies and cognitive decline in obesity with or without estrogen deprivation.

Human Blood Bacteriome: Eubiotic and Dysbiotic States in Health and Diseases.

The human gut microbiome is acknowledged as being associated with homeostasis and the pathogenesis of several diseases. Conventional culture techniques are limited in that they cannot culture the commensals; however, next-generation sequencing has facilitated the discovery of the diverse and delicate microbial relationship in body sites and blood. Increasing evidence regarding the blood microbiome has revolutionized the concept of sterility and germ theory in circulation. Among the types of microbial communities in the blood, bacteriomes associated with many health conditions have been thoroughly investigated. Blood bacterial profiles in healthy subjects are identified as the eubiotic blood bacteriome, whereas the dysbiotic blood bacteriome represents the change in bacterial characteristics in subjects with diseases showing deviations from the eubiotic profiles. The blood bacterial characteristics in each study are heterogeneous; thus, the association between eubiotic and dysbiotic blood bacteriomes and health and disease is still debatable. Thereby, this review aims to summarize and discuss the evidence concerning eubiotic and dysbiotic blood bacteriomes characterized by next-generation sequencing in human studies. Knowledge pertaining to the blood bacteriome will transform the concepts around health and disease in humans, facilitating clinical implementation in the near future.

Gut dysbiosis develops before metabolic disturbance and cognitive decline in high-fat diet-induced obese condition.

OBJECTIVES: High-fat diet (HFD) consumption caused metabolic disturbance, gut dysbiosis, brain pathology, microglia hyperactivity, and cognitive decline. However, the exact timeline of these abnormalities following HFD consumption is still elusive. Therefore, the aim of this study was to test the hypothesis that gut dysbiosis, peripheral inflammation, and peripheral insulin resistance occur before the brain inflammatory response, hippocampal synaptic dysplasticity, oxidative stress, apoptosis, and cognitive impairment in HFD-fed rats. METHODS: Male Wistar rats received either a normal diet or an HFD for 2, 8, 12, 20, or 40 wk. At the end of each time point, cognitive functions and metabolic parameters were determined. Gut microbiota, brain immune cell activity, amyloid-ß level, microglia morphology, hippocampal reactive oxygen species and apoptosis, hippocampal synaptic plasticity, and dendritic spine density were measured. RESULTS: We found that HFD-fed rats developed gut dysbiosis at week 2 and peripheral insulin resistance at week 8. Rats fed an HFD for 12 wk displayed hippocampal synaptic dysplasticity, decreased dendritic spine density, an elevation of ionized calcium-binding adapter molecule 1+ cells, increased hippocampal reactive oxygen species levels and hippocampal apoptosis with cognitive decline. The decreased percentage of resident microglia and increased percentage of infiltrated macrophage were observed at weeks 20 and 40. Surprisingly, brain amyloid-ß levels were increased after 40 wk of an HFD diet. CONCLUSIONS: These findings demonstrated that gut dysbiosis develops in the earliest phase of consumption of an HFD, followed by brain pathology, which leads to cognitive decline in obese insulin-resistant rats. Therefore, an improvement in gut dysbiosis should provide beneficial effects in the prevention of neuropathology and cognitive decline in the obese.