FAST and Agile-the MASLD drift: Validation of Agile 3+, Agile 4 and FAST scores in 246 biopsy-proven NAFLD patients meeting MASLD criteria of prevalent caucasian origin.

BACKGROUND: MASLD is a prevalent chronic liver condition with substantial clinical implications. This study aimed to assess the effectiveness of three new, elastography-based, scoring systems for advanced fibrosis ≥F3 (Agile 3+), cirrhosis F4 (Agile 4), and fibrotic NASH: NASH + NAS ≥4 + F≥2 (FAST score), in a cohort of biopsy-proven NAFLD meeting MASLD criteria. Our secondary aim was to compare their diagnostic performances with those of other fibrosis prediction tools: LSM-VCTE alone, and common, easily available scores (FIB-4 or APRI). METHODS: Single-center, retrospective study, on consecutive patients with baseline laboratory tests, liver biopsy, and reliable LSM-VCTE measurements. The discrimination between tests was evaluated by analyzing the AUROCs. Dual cut-off approaches were applied to rule-out and rule-in ≥F3, F4 and fibrotic NASH. We tested previously reported cut-off values and provided our best thresholds to achieve Se ≥85%, Se ≥90%, and Sp ≥90%, Sp ≥95%. RESULTS: Among 246 patients, 113 (45.9%) were women, and 75 (30.5%) presented diabetes. Agile 3+ and Agile 4 demonstrated excellent performance in identifying ≥F3 and F4, achieving AUROCs of 0.909 and 0.968, while the FAST score yielded acceptable results in distinguishing fibrotic NASH. When compared to FIB-4 and LSM-VCTE, both Agile 3+ and Agile 4 performed better than FIB-4 and had a similar performance to LSM-VCTE, but with higher diagnostic accuracy, hence reducing the grey zone. CONCLUSION: Agile 3+ and Agile 4 are reliable, non-invasive tests for identifying advanced fibrosis or cirrhosis in MASLD patients, while FAST score demonstrates moderate performance in identifying fibrotic NASH.

New-onset Diabetes Mellitus after EUS-guided Drainage with LAMS: A Pilot Study.

BACKGROUND AND AIMS: Walled-off necrosis (WON) is a serious complication of severe pancreatitis, patients with necrotizing pancreatitis having an increased risk of developing diabetes mellitus (DM). The aim of this study was to assess the frequency of new-onset diabetes (NOD) in patients with symptomatic WON after endoscopic ultrasound (EUS)-guided drainage with lumen-apposing metal stents (LAMS). METHODS: We retrospectively analyzed a prospectively collected database of patients with symptomatic WON treated by EUS-guided drainage with LAMS in a tertiary referral center. The patients were followed-up for at least 12 months after stent removal. These patients were compared with age- and sex-matched asymptomatic WON controls without interventional treatment and healthy controls to assess the one-year occurrence of DM. Diabetes was defined according to the American Diabetes Association criteria. RESULTS: Of the 50 patients with symptomatic WON included in the study (male/female ratio, 33:17; median age, 60 years), 13 patients (26%) had pre-existing DM and were excluded. Ten of the remaining 37 patients (27%) without prior DM developed NOD within one year after stent removal, this frequency being higher than in asymptomatic WON controls (18.9%, p=0.581) and healthy controls (2%, p = 0.002). In the symptomatic WON group, NOD patients compared to non-DM patients were older (63.5 vs. 56 years old, p=0.042), had more frequent necrosis > 50% of the pancreatic parenchyma (p=0.002) and had a body-tail location of WON (p<0.001). On multivariate analysis, the number of direct endoscopic necrosectomy (DEN) sessions was the only significant factor for NOD occurrence (OR=7.05, p=0.010). NOD patients had poor glycemic control and required more DEN sessions to achieve WON resolution than patients with prior DM (p=0.017). CONCLUSIONS: In patients with symptomatic WON treated by EUS-guided drainage, DM occurred in 27% of previously non-diabetic patients within one year of follow-up. Patients with extensive pancreatic necrosis were more likely to develop NOD, a high number of DEN sessions being a significant risk factor for NOD occurrence.

How to Identify Advanced Fibrosis in Adult Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) Using Ultrasound Elastography-A Review of the Literature and Proposed Multistep Approach.

Non-alcoholic fatty liver disease (NAFLD), and its progressive form, non-alcoholic steatohepatitis (NASH), represent, nowadays, real challenges for the healthcare system. Liver fibrosis is the most important prognostic factor for NAFLD, and advanced fibrosis is associated with higher liver-related mortality rates. Therefore, the key issues in NAFLD are the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis. We critically reviewed the ultrasound (US) elastography techniques for the quantitative characterization of fibrosis, steatosis, and inflammation in NAFLD and NASH, with a specific focus on how to differentiate advanced fibrosis in adult patients. Vibration-controlled transient elastography (VCTE) is still the most utilized and validated elastography method for liver fibrosis assessment. The recently developed point shear wave elastography (pSWE) and two-dimensional shear wave elastography (2D-SWE) techniques that use multiparametric approaches could bring essential improvements to diagnosis and risk stratification.

Nanotechnology Involved in Treating Urinary Tract Infections: An Overview.

Considered as the most frequent contaminations that do not require hospitalization, urinary tract infections (UTIs) are largely known to cause significant personal burdens on patients. Although UTIs overall are highly preventable health issues, the recourse to antibiotics as drug treatments for these infections is a worryingly spread approach that should be addressed and gradually overcome in a contemporary, modernized healthcare system. With a virtually alarming global rise of antibiotic resistance overall, nanotechnologies may prove to be the much-needed 'lifebuoy' that will eventually suppress this prejudicial phenomenon. This review aims to present the most promising, currently known nano-solutions, with glimpses on clinical and epidemiological aspects of the UTIs, prospective diagnostic instruments, and non-antibiotic treatments, all of these engulfed in a comprehensive overview.

Nanocarriers for Drug Delivery: An Overview with Emphasis on Vitamin D and K Transportation.

Mounting evidence shows that supplementation with vitamin D and K or their analogs induces beneficial effects in various diseases, e.g., osteoarticular, cardiovascular, or carcinogenesis. The use of drugs delivery systems via organic and inorganic nanocarriers increases the bioavailability of vitamins and analogs, enhancing their cellular delivery and effects. The nanotechnology-based dietary supplements and drugs produced by the food and pharmaceutical industries overcome the issues associated with vitamin administration, such as stability, absorption or low bioavailability. Consequently, there is a continuous interest in optimizing the carriers' systems in order to make them more efficient and specific for the targeted tissue. In this pioneer review, we try to circumscribe the most relevant aspects related to nanocarriers for drug delivery, compare different types of nanoparticles for vitamin D and K transportation, and critically address their benefits and disadvantages.