International study of the prevalence and outcomes of infection in intensive care units

Importance Nonalcoholic steatohepatitis (NASH) is the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD) and is associated with disease progression, development of cirrhosis, and need for liver transplant. Despite its importance, NASH is underrecognized in clinical practice. Observations NASH affects an estimated 3% to 6% of the US population and the prevalence is increasing. NASH is strongly associated with obesity, dyslipidemia, type 2 diabetes, and metabolic syndrome. Although a number of noninvasive tests and scoring systems exist to characterize NAFLD and NASH, liver biopsy is the only accepted method for diagnosis of NASH. Currently, no NASH-specific therapies are approved by the US Food and Drug Administration. Lifestyle modification is the mainstay of treatment, including dietary changes and exercise, with the primary goal being weight loss. Substantial improvement in histologic outcomes, including fibrosis, is directly correlated with increasing weight loss. In some cases, bariatric surgery may be indicated to achieve and maintain the necessary degree of weight loss required for therapeutic effect. An estimated 20% of patients with NASH will develop cirrhosis, and NASH is predicted to become the leading indication for liver transplants in the US. The mortality rate among patients with NASH is substantially higher than the general population or patients without this inflammatory subtype of NAFLD, with annual all-cause mortality rate of 25.56 per 1000 person-years and a liver-specific mortality rate of 11.77 per 1000 person-years. Conclusions and Relevance Nonalcoholic steatohepatitis affects 3% to 6% of the US population, is more prevalent in patients with metabolic disease and obesity, progresses to cirrhosis in approximately 20% of cases, and is associated with increased rates of liver-specific and overall mortality. Early identification and targeted treatment of patients with nonalcoholic steatohepatitis are needed to improve patient outcomes, including directing patients toward intensive lifestyle modification to promote weight loss and referral for bariatric surgery as indicated for management of obesity and metabolic disease.

https://jamanetwork.com/journals/jama/articlepdf/2763297/jama_sheka_2020_rv_200001.pdf

Nonalcoholic Steatohepatitis: A Review.

Gut microbiota dysbiosis has been repeatedly observed in obesity and type 2 diabetes mellitus, two metabolic diseases strongly intertwined with non-alcoholic fatty liver disease (NAFLD). Animal studies have demonstrated a potential causal role of gut microbiota in NAFLD. Human studies have started to describe microbiota alterations in NAFLD and have found a few consistent microbiome signatures discriminating healthy individuals from those with NAFLD, non-alcoholic steatohepatitis or cirrhosis. However, patients with NAFLD often present with obesity and/or insulin resistance and type 2 diabetes mellitus, and these metabolic confounding factors for dysbiosis have not always been considered. Patients with different NAFLD severity stages often present with heterogeneous lesions and variable demographic characteristics (including age, sex and ethnicity), which are known to affect the gut microbiome and have been overlooked in most studies. Finally, multiple gut microbiome sequencing tools and NAFLD diagnostic methods have been used across studies that could account for discrepant microbiome signatures. This Review provides a broad insight into microbiome signatures for human NAFLD and explores issues with disentangling these signatures from underlying metabolic disorders. More advanced metagenomics and multi-omics studies using system biology approaches are needed to improve microbiome biomarkers.

/pdf/gut-microbiota-and-human-nafld-disentangling-microbial-2b62qctp4x.pdf

Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders

Non-alcoholic fatty liver (NAFLD) is the most common liver disease worldwide, progressing from simple steatosis to necroinflammation and fibrosis (leading to non-alcoholic steatohepatitis, NASH), and in some cases to cirrhosis and hepatocellular carcinoma Inflammation, oxidative stress and insulin resistance are involved in NAFLD development and progression NAFLD has been associated with several cardiovascular (CV) risk factors including obesity, dyslipidemia, hyperglycemia, hypertension and smoking NAFLD is also characterized by atherogenic dyslipidemia, postprandial lipemia and high-density lipoprotein (HDL) dysfunction Most importantly, NAFLD patients have an increased risk for both liver and CV disease (CVD) morbidity and mortality In this narrative review, the associations between NAFLD, dyslipidemia and vascular disease in NAFLD patients are discussed NAFLD treatment is also reviewed with a focus on lipid-lowering drugs Finally, future perspectives in terms of both NAFLD diagnostic biomarkers and therapeutic targets are considered

Non-alcoholic fatty liver disease and dyslipidemia: An update

Given the high prevalence and rising incidence of non-alcoholic fatty liver disease (NAFLD), the absence of approved therapies is striking. Although the mainstay of treatment of NAFLD is weight loss, it is hard to maintain, prompting the need for pharmacotherapy as well. A greater understanding of disease pathogenesis in recent years was followed by development of new classes of medications, as well as potential repurposing of currently available agents. NAFLD therapies target four main pathways. The dominant approach is targeting hepatic fat accumulation and the resultant metabolic stress. Medications in this group include peroxisome proliferator-activator receptor agonists (eg, pioglitazone, elafibranor, saroglitazar), medications targeting the bile acid-farnesoid X receptor axis (obeticholic acid), inhibitors of de novo lipogenesis (aramchol, NDI-010976), incretins (liraglutide) and fibroblast growth factor (FGF)-21 or FGF-19 analogues. A second approach is targeting the oxidative stress, inflammation and injury that follow the metabolic stress. Medications from this group include antioxidants (vitamin E), medications with a target in the tumour necrosis factor α pathway (emricasan, pentoxifylline) and immune modulators (amlexanox, cenicriviroc). A third group has a target in the gut, including antiobesity agents such as orlistat or gut microbiome modulators (IMM-124e, faecal microbial transplant, solithromycin). Finally, as the ongoing injury leads to fibrosis, the harbinger of liver-related morbidity and mortality, antifibrotics (simtuzumab and GR-MD-02) will be an important element of therapy. It is very likely that in the next few years several medications will be available to clinicians treating patients with NAFLD across the entire spectrum of disease.

/pdf/current-and-upcoming-pharmacotherapy-for-non-alcoholic-fatty-2qbpkaa5hx.pdf

Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease

The efficacy and safety of statins for the treatment of non-alcoholic fatty liver disease.

Macrolides and viral infections: focus on azithromycin in COVID-19 pathology.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial and venous thrombotic manifestations and/or pregnancy-related complications in patients with persistently high antiphospholipid antibodies (aPL), the most common being represented by anticardiolipin antibodies (aCL), anti-beta 2 glycoprotein-I (aβ2GPI), and lupus anticoagulant (LAC). A growing number of studies have showed that, in some cases, patients may present with clinical features of APS but with temporary positive or persistently negative titers of aPL. For these patients, the definition of seronegative APS (SN-APS) has been proposed. Nevertheless, the negativity to classic aPL criteria does not imply that other antibodies may be present or involved in the onset of thrombosis. The diagnosis of SN-APS is usually made by exclusion, but its recognition is important to adopt the most appropriate anti-thrombotic strategy to reduce the rate of recurrences. This research is in continuous development as the clinical relevance of these antibodies is far from being completely clarified. The most studied antibodies are those against phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, vimentin/cardiolipin complex, and annexin A5. Moreover, the assays to measure the levels of these antibodies have not yet been standardized. In this review, we will summarize the evidence on the most studied non-criteria aPL, their potential clinical relevance, and the antithrombotic therapeutic strategies available in the setting of APS and SN-APS.

/pdf/seronegative-antiphospholipid-syndrome-refining-the-value-of-5gcbc82jsy.pdf

Seronegative antiphospholipid syndrome: refining the value of "non-criteria" antibodies for diagnosis and clinical management.

Supermagnetic Iron Oxide Nanoparticles (SPIONs) are nanoparticles that have an iron oxide core and a functionalized shell. SPIONs have recently raised much interest in the scientific community, given their exciting potential diagnostic and theragnostic applications. The possibility to modify their surface and the characteristics of their core make SPIONs a specific contrast agent for magnetic resonance imaging but also an intriguing family of tracer for nuclear medicine. An example is 68Ga-radiolabeled bombesin-conjugated to superparamagnetic nanoparticles coated with trimethyl chitosan that is selective for the gastrin-releasing peptide receptors. These receptors are expressed by several human cancer cells such as breast and prostate neoplasia. Since the coating does not interfere with the properties of the molecules bounded to the shell, it has been proposed to link SPIONs with antibodies. SPIONs can be used also to monitor the biodistribution of mesenchymal stromal cells and take place in various applications. The aim of this review of literature is to analyze the diagnostic aspect of SPIONs in magnetic resonance imaging and in nuclear medicine, with a particular focus on sentinel lymph node applications. Moreover, it is taken into account the possible toxicity and the effects on human physiology to determine the SPIONs’ safety.

New Frontiers in Molecular Imaging with Superparamagnetic Iron Oxide Nanoparticles (SPIONs): Efficacy, Toxicity, and Future Applications

Cerebrovascular diseases are well established causes of cognitive impairment. Different etiologic entities, such as vascular dementia (VaD), vascular cognitive impairment, subcortical (ischemic) VaD, and vascular cognitive disorder, are included in the umbrella definition of vascular cognitive impairment and dementia (VCID). Because of the variability of VCID clinical presentation, there is no agreement on criteria defining the neuropathological threshold of this disorder. In fact, VCID is characterized by cerebral hemodynamic alteration which ranges from decreased cerebral blood flow to small vessels disease and involves a multifactorial process that leads to demyelination and gliosis, including blood-brain barrier disruption, hypoxia, and hypoperfusion, oxidative stress, neuroinflammation and alteration on neurovascular unit coupling, cerebral microbleeds, or superficial siderosis. Numerous criteria for the definition of VaD have been described: the National Institute of Neurological Disorders and Stroke Association Internationale pour Recherche'-et-l'Enseignement en Neurosciences criteria, the State of California Alzheimer's Disease Diagnostic and Treatment Centers criteria, DSM-V criteria, the Diagnostic Criteria for Vascular Cognitive Disorders (a VASCOG Statement), and Vascular Impairment of Cognition Classification Consensus Study. Neuroimaging is fundamental for definition and diagnosis of VCID and should be used to assess the extent, location, and type of vascular lesions. MRI is the most sensible technique, especially if used according to standardized protocols, even if CT plays an important role in several conditions. Functional neuroimaging, in particular functional MRI and PET, may facilitate differential diagnosis among different forms of dementia. This systematic review aims to explore the state of the art and future perspective of non-invasive diagnostics of VCID.

Arianna Pani

Papers

The efficacy and safety of statins for the treatment of non-alcoholic fatty liver disease.

Macrolides and viral infections: focus on azithromycin in COVID-19 pathology.

Seronegative antiphospholipid syndrome: refining the value of "non-criteria" antibodies for diagnosis and clinical management.

New Frontiers in Molecular Imaging with Superparamagnetic Iron Oxide Nanoparticles (SPIONs): Efficacy, Toxicity, and Future Applications

Neuroimaging in Vascular Cognitive Impairment and Dementia: A Systematic Review.