Alcohol, Inflammation, and Microbiota in Alcoholic Liver Disease.

Alcoholic liver disease (ALD) is a consequence of excessive alcohol use. According to many studies, alcohol represents a significant socioeconomic and health risk factor in today's population. According to data from the World Health Organization, there are about 75 million people who have alcohol disorders, and it is well known that its use leads to serious health problems. ALD is a multimodality spectrum that includes alcoholic fatty liver disease (AFL) and alcoholic steatohepatitis (ASH), consequently leading to liver fibrosis and cirrhosis. In addition, the rapid progression of alcoholic liver disease can lead to alcoholic hepatitis (AH). Alcohol metabolism produces toxic metabolites that lead to tissue and organ damage through an inflammatory cascade that includes numerous cytokines, chemokines, and reactive oxygen species (ROS). In the process of inflammation, mediators are cells of the immune system, but also resident cells of the liver, such as hepatocytes, hepatic stellate cells, and Kupffer cells. These cells are activated by exogenous and endogenous antigens, which are called pathogen and damage-associated molecular patterns (PAMPs, DAMPs). Both are recognized by Toll-like receptors (TLRs), which activation triggers the inflammatory pathways. It has been proven that intestinal dysbiosis and disturbed integrity of the intestinal barrier perform a role in the promotion of inflammatory liver damage. These phenomena are also found in chronic excessive use of alcohol. The intestinal microbiota has an important role in maintaining the homeostasis of the organism, and its role in the treatment of ALD has been widely investigated. Prebiotics, probiotics, postbiotics, and symbiotics represent therapeutic interventions that can have a significant effect on the prevention and treatment of ALD.

Aging of Liver in Its Different Diseases.

The proportion of elderly people in the world population is constantly increasing. With age, the risk of numerous chronic diseases and their complications also rises. Research on the subject of cellular senescence date back to the middle of the last century, and today we know that senescent cells have different morphology, metabolism, phenotypes and many other characteristics. Their main feature is the development of senescence-associated secretory phenotype (SASP), whose pro-inflammatory components affect tissues and organs, and increases the possibility of age-related diseases. The liver is the main metabolic organ of our body, and the results of previous research indicate that its regenerative capacity is greater and that it ages more slowly compared to other organs. With age, liver cells change under the influence of various stressors and the risk of developing chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH) and hepatocellular carcinoma (HCC) increases. It has been proven that these diseases progress faster in the elderly population and in some cases lead to end-stage liver disease that requires transplantation. The treatment of elderly people with chronic liver diseases is a challenge and requires an individual approach as well as new research that will reveal other safe and effective therapeutic modalities.

Point-of-Care Echocardiographic Characteristics of COVID-19 Patients with Pulmonary Embolism.

INTRODUCTION: Thrombotic complications, such as pulmonary embolism, are common in COVID-19 patients. Point-of-care ultrasound is a highly recommended tool for orientation in critically ill patients with suspected or confirmed complications. METHODS: An observational study was conducted on 32 consecutive patients with confirmed pulmonary embolism and COVID-19 infection treated in the Intensive Care Unit of the University Hospital Medical Center "Bezanijska kosa", Belgrade, Serbia, between April 2021 and March 2022. Predictors of the need for oxygen support were determined, while point-of-care echocardiographic parameters and various anamnestic, laboratory, and clinically significant parameters were correlated with the Pulmonary Embolism Severity Index (PESI) score. RESULTS: More than two-thirds of patients in our study had PE symptoms present at hospital admission (68.8%). The majority of patients had segmental pulmonary embolism (48.4%), with high to very high PESI score values in 31.3% of patients. Pneumonia was present in 68.8% of the study population. The PESI score was negatively correlated with diastolic blood pressure and SaO2 at the time of PE diagnosis, LV ejection fraction, and PVAT. A positive correlation was found between the PESI score, maximum CRP, and D-dimer at the time of PTE diagnosis. A larger right ventricular diameter was associated with a greater need for oxygen support. CONCLUSION: Point-of-care echocardiography is a valuable tool for the risk assessment of COVID-19 patients with pulmonary embolism. Right ventricular size stood out as a significant marker of disease severity.

Factors Predicting Malignant Occurrence and Polyp Recurrence after the Endoscopic Resection of Large Colorectal Polyps: A Single Center Experience.

Background: The aim of this study was to identify risk factors contributing to the malignancy of colorectal polyps, as well as risk factors for recurrence after the successful endoscopic mucosal resection of large colorectal polyps in a referral center. Materials and Methods: This retrospective cohort study was performed in patients diagnosed with large (≥20 mm diameter) colorectal polyps and treated in the period from January 2014 to December 2019 at the University Hospital Medical Center Bezanijska Kosa, Belgrade, Serbia. Based on the endoscopic evaluation and classification of polyps, the following procedures were performed: en bloc resection, piecemeal resection or surgical treatment. Results: A total of 472 patients with large colorectal polyps were included in the study. The majority of the study population were male (62.9%), with a mean age of 65.7 ± 10.8 years. The majority of patients had one polyp (73.7%) less than 40 mm in size (74.6%) sessile morphology (46.4%), type IIA polyps (88.2%) or polyps localized in the descending colon (52.5%). The accessibility of the polyp was complicated in 17.4% of patients. En bloc resection was successfully performed in 61.0% of the patients, while the rate of piecemeal resection was 26.1%. Due to incomplete endoscopic resection, surgery was performed in 5.1% of the patients, while 7.8% of the patients were referred to surgery directly. Hematochezia (p = 0.001), type IIB polyps (p < 0.001) and complicated polyp accessibility (p = 0.002) were significant independent predictors of carcinoma presence in a multivariate logistic regression analysis. Out of the 472 patients enrolled in the study, 364 were followed after endoscopic resection for colorectal polyp recurrence, which was observed in 30 patients (8.2%) during follow-up. Piecemeal resection (p = 0.048) and incomplete resection success (p = 0.013) were significant independent predictors of polyp recurrence in the multivariate logistic regression analysis. Conclusions: Whenever an endoscopist encounters a complex colorectal lesion (i.e., a polyp with complicated accessibility), polyp size > 40 mm, the Laterally Spreading Tumor nongranular (LST-NG) morphological type, type IIB polyps or the presence of hematochezia, malignancy risk should be considered before making the decision to either resect, refer to an advanced endoscopist or perform surgery.

Point-of-Care Abdominal Ultrasonography (POCUS) on the Way to the Right and Rapid Diagnosis.

Point-of-Care ultrasound (POCUS) is based on target ultrasound that is performed wherever a patient is being treated, and by a non-radiologist directly involved in the patient's care. It is used either for quick diagnosis or procedural guidance. Abdominal pain is one of the most common complaints in emergency departments, and POCUS can help in the differentiation of patients who need additional diagnostic tests or hospital treatment, which eventually reduces the overall costs of health care. POCUS has high sensitivity and specificity in abdominal pathology, it can be helpful in the evaluation of biliary, intestinal, and urinary tract, and it is especially used in trauma. Additionally, the gold standard for abdominal aortic aneurysm detection, follow up and screening is precisely this diagnostic procedure. Unfortunately, the quality of ultrasound examination can be affected by the experience of the physician performing it and the patient's body weight. There is no doubt that POCUS is being increasingly recognized, but all motivated physicians should be provided with dedicated tutors and enough time for learning. This would certainly help to implement this diagnostic method as a routine in emergency and critical care departments, and significantly shorten the time until definitive diagnosis.

Elevated Transaminases as Predictors of COVID-19 Pneumonia Severity.

BACKGROUND: This study aimed to calculate the frequency of elevated liver enzymes in hospitalized patients with coronavirus disease 2019 (COVID-19) infection and to test if liver enzyme biochemistry levels on admission could predict the computed tomography (CT) scan severity score of bilateral interstitial pneumonia. METHODS: This single-center study comprised of 323 patients including their demographic data, laboratory analyses, and radiological findings. All the information was taken from electronic health records, followed by statistical analysis. RESULTS: Out of 323 patients, 115 of them (35.60%) had aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) over 40 U/L on admission. AST was the best predictor of CT scan severity score of bilateral interstitial pneumonia (R2 = 0.313, Adjusted R2 = 0.299). CT scan severity score in the peak of the infection could be predicted with the value of AST, neutrophils, platelets, and monocytes count (R2 = 0.535, Adjusted R2 = 0.495). CONCLUSION: AST, neutrophils, platelets, and monocytes count on admission can account for almost half (49.5%) of the variability in CT scan severity score at peak of the disease, predicting the extensiveness of interstitial pneumonia related to COVID-19 infection. Liver enzymes should be closely monitored in order to stratify COVID-19 patients with a higher risk of developing severe forms of the disease and to plan the beforehand step-up treatment.

Lipotoxicity as the Leading Cause of Non-Alcoholic Steatohepatitis.

The emerging issues nowadays are non-alcoholic fatty liver disease (NAFLD) and its advanced stage non-alcoholic steatohepatitis (NASH), which further can be a predisposing factor for chronic liver complications, such as cirrhosis and/or development of hepatocellular carcinoma (HCC). Liver lipotoxicity can influence the accumulation of reactive oxygen species (ROS), so oxidative stress is also crucial for the progression of NASH. Moreover, NASH is in strong connection with metabolic disorders, and supporting evidence shows that insulin resistance (IR) is in a close relation to NAFLD, as it is involved in the progression to NASH and further progression to hepatic fibrosis. The major issue is that, at the moment, NASH treatment is based on lifestyle changes only due to the fact that no approved therapeutic options are available. The development of new therapeutic strategies should be conducted towards the potential NAFLD and NASH treatment by the modulation of IR but also by dietary antioxidants. As it seems, NASH is going to be the leading indication for liver transplantation as a consequence of increased disease prevalence and the lack of approved treatment; thus, an effective solution is needed as soon as possible.