Noncommunicable diseases, climate change and iniquities: What COVID-19 has taught us about syndemic.

BACKGROUND: COVID-19 is generating clinical challenges, lifestyle changes, economic consequences. The pandemic imposes to familiarize with concepts as prevention, vulnerability and resilience. METHODS: We analysed and reviewed the most relevant papers in the MEDLINE database on syndemic, noncommunicable diseases, pandemic, climate changes, pollution, resilience, vulnerability, health costs, COVID-19. RESULTS: We discuss that comprehensive strategies must face multifactorial consequences since the pandemic becomes syndemic due to interactions with noncommunicable diseases, climate changes and iniquities. The lockdown experience, on the other hand, demonstrates that it is rapidly possible to reverse epidemiologic trends and to reduce pollution. The worst outcome is evident in eight highly industrialized nations, where 12% of the world population experienced about one-third of all COVID-19-deaths worldwide. Thus, a great economic power has not been fully protective, and a change of policy is obviously needed to avoid irreversible consequences. CONCLUSIONS: We are accumulating unhealthy populations living in unhealthy environments and generating unhealthy offspring. The winning policy should tackle structural inequities through a syndemic approach, to protect vulnerable populations from present and future harms.

Mitochondria Matter: Systemic Aspects of Nonalcoholic Fatty Liver Disease (NAFLD) and Diagnostic Assessment of Liver Function by Stable Isotope Dynamic Breath Tests.

The liver plays a key role in systemic metabolic processes, which include detoxification, synthesis, storage, and export of carbohydrates, lipids, and proteins. The raising trends of obesity and metabolic disorders worldwide is often associated with the nonalcoholic fatty liver disease (NAFLD), which has become the most frequent type of chronic liver disorder with risk of progression to cirrhosis and hepatocellular carcinoma. Liver mitochondria play a key role in degrading the pathways of carbohydrates, proteins, lipids, and xenobiotics, and to provide energy for the body cells. The morphological and functional integrity of mitochondria guarantee the proper functioning of ß-oxidation of free fatty acids and of the tricarboxylic acid cycle. Evaluation of the liver in clinical medicine needs to be accurate in NAFLD patients and includes history, physical exam, imaging, and laboratory assays. Evaluation of mitochondrial function in chronic liver disease and NAFLD is now possible by novel diagnostic tools. "Dynamic" liver function tests include the breath test (BT) based on the use of substrates marked with the non-radioactive, naturally occurring stable isotope 13C. Hepatocellular metabolization of the substrate will generate 13CO2, which is excreted in breath and measured by mass spectrometry or infrared spectroscopy. Breath levels of 13CO2 are biomarkers of specific metabolic processes occurring in the hepatocyte cytosol, microsomes, and mitochondria. 13C-BTs explore distinct chronic liver diseases including simple liver steatosis, non-alcoholic steatohepatitis, liver fibrosis, cirrhosis, hepatocellular carcinoma, drug, and alcohol effects. In NAFLD, 13C-BT use substrates such as α-ketoisocaproic acid, methionine, and octanoic acid to assess mitochondrial oxidation capacity which can be impaired at an early stage of disease. 13C-BTs represent an indirect, cost-effective, and easy method to evaluate dynamic liver function. Further applications are expected in clinical medicine. In this review, we discuss the involvement of liver mitochondria in the progression of NAFLD, together with the role of 13C-BT in assessing mitochondrial function and its potential use in the prevention and management of NAFLD.

Recent advances in understanding and managing cholesterol gallstones.

The high prevalence of cholesterol gallstones, the availability of new information about pathogenesis, and the relevant health costs due to the management of cholelithiasis in both children and adults contribute to a growing interest in this disease. From an epidemiologic point of view, the risk of gallstones has been associated with higher risk of incident ischemic heart disease, total mortality, and disease-specific mortality (including cancer) independently from the presence of traditional risk factors such as body weight, lifestyle, diabetes, and dyslipidemia. This evidence points to the existence of complex pathogenic pathways linking the occurrence of gallstones to altered systemic homeostasis involving multiple organs and dynamics. In fact, the formation of gallstones is secondary to local factors strictly dependent on the gallbladder (that is, impaired smooth muscle function, wall inflammation, and intraluminal mucin accumulation) and bile (that is, supersaturation in cholesterol and precipitation of solid crystals) but also to "extra-gallbladder" features such as gene polymorphism, epigenetic factors, expression and activity of nuclear receptors, hormonal factors (in particular, insulin resistance), multi-level alterations in cholesterol metabolism, altered intestinal motility, and variations in gut microbiota. Of note, the majority of these factors are potentially manageable. Thus, cholelithiasis appears as the expression of systemic unbalances that, besides the classic therapeutic approaches to patients with clinical evidence of symptomatic disease or complications (surgery and, in a small subgroup of subjects, oral litholysis with bile acids), could be managed with tools oriented to primary prevention (changes in diet and lifestyle and pharmacologic prevention in subgroups at high risk), and there could be relevant implications in reducing both prevalence and health costs.