Endothelial dysfunction (ED) is the in the background of multiple metabolic diseases and a key process in liver disease progression and cirrhosis decompensation. ED affects liver sinusoidal endothelial cells (LSECs) in response to different damaging agents, causing their progressive dedifferentiation, unavoidably associated with an increase in intrahepatic resistance that leads to portal hypertension and hyperdynamic circulation with increased cardiac output and low peripheral artery resistance. These changes are driven by a continuous interplay between different hepatic cell types, invariably leading to increased reactive oxygen species (ROS) formation, increased release of pro-inflammatory cytokines and chemokines, and reduced nitric oxide (NO) bioavailability, with a subsequent loss of proper vascular tone regulation and fibrosis development. ED evaluation is often accomplished by serum markers and the flow-mediated dilation (FMD) measurement of the brachial artery to assess its NO-dependent response to shear stress, which usually decreases in ED. In the context of liver cirrhosis, the ED assessment could help understand the complex hemodynamic changes occurring in the early and late stages of the disease. However, the instauration of a hyperdynamic state and the different NO bioavailability in intrahepatic and systemic circulation—often defined as the NO paradox—must be considered confounding factors during FMD analysis. The primary purpose of this review is to describe the main features of ED and highlight the key findings of the dynamic and intriguing relationship between ED and liver disease. We will also focus on the significance of FMD evaluation in this setting, pointing out its key role as a therapeutic target in the never-ending battle against liver cirrhosis progression.

Antibiotics, widely used medications that have significantly increased life expectancy, possess a broad range of effects beyond their primary antibacterial activity. While some are recognized as adverse events, others have demonstrated unexpected benefits. These adjunctive effects, which have been defined as “pleiotropic” in the case of other pharmacological classes, include immunomodulatory properties and the modulation of the microbiota. Specifically, macrolides, tetracyclines, and fluoroquinolones have been shown to modulate the immune system in both acute and chronic conditions, including autoimmune disorders (e.g., rheumatoid arthritis, spondyloarthritis) and chronic inflammatory pulmonary diseases (e.g., asthma, chronic obstructive pulmonary disease). Azithromycin, in particular, is recommended for the long-term treatment of chronic inflammatory pulmonary diseases due to its well-established immunomodulatory effects. Furthermore, antibiotics influence the human microbiota. Rifaximin, for example, exerts a eubiotic effect that enhances the balance between the gut microbiota and the host immune cells and epithelial cells. These pleiotropic effects offer new therapeutic opportunities by interacting with human cells, signaling molecules, and bacteria involved in non-infectious diseases like spondyloarthritis and inflammatory bowel diseases. The aim of this review is to explore the pleiotropic potential of antibiotics, from molecular and cellular evidence to their clinical application, in order to optimize their use. Understanding these effects is essential to ensure careful use, particularly in consideration of the threat of antimicrobial resistance.

Background: Lynch syndrome (LS) is a genetic disease with increased risk of colorectal cancer and other malignancies. There are few reported cases of thyroid cancer in LS patients. The aim of this study is to investigate the presence of thyroid nodules in LS patients and to explore their association with the genetic features of the disease. Methods: A retrospective and descriptive analysis was conducted to include all LS patients followed at the CEMAD (Centro Malattie Apparato Digerente) of Fondazione Policlinico Universitario A. Gemelli IRCCS. The characteristics of LS disease, gene mutations, and previous history of thyroid disease were evaluated. Majority of patients underwent thyroid ultrasound (US), and nodule cytology was performed when needed. Results: Of a total of 139 patients with LS, 110 patients were included in the study. A total of 103 patients (74%) underwent thyroid ultrasound examinations, and 7 patients (5%) had a previous history of thyroid disease (cancer or multinodular goiter). The mean age was 51.9 years. Thyroid nodules were found in 62 patients (60%) who underwent US, and 9 of them (14%) had suspicious features of malignancy, inducing a fine-needle aspiration biopsy. A cytologic analysis classified 7 of 9 cases (78%) as TIR2 and 2 (22%) as TIR3a. Between patients with nodular thyroid disease (single nodule, multinodular goiter, and cancer), most of them (25 patients, 36% of total) were carriers of the MSH6 mutation, while 22 (32%), 17 (24%), and 5 (7%) had MSH2, MLH1, and PMS2 mutations, respectively. Conclusions: A high prevalence of thyroid nodules was found in patients with LS, especially in MSH6-carrying patients. Performing at least one thyroid ultrasound examination is suggested for the detection of nodular thyroid disease in LS patients. Systematic investigations are needed to estimate their prevalence, features, and risk of malignant transformation.

Background: Liver involvement in adults with acute myeloid leukemia is uncommon. Most of the case reports describe acute liver failure or obstructive jaundice, while acute hepatitis is rarely mentioned. We report a patient with acute myeloid leukemia who presented with clinical, biochemical, and radiological signs of acute hepatitis that totally regressed after chemotherapy. Case presentation: A 38-year-old Caucasian man presented with fever, cough, and mild fatigue. Laboratory workup showed anemia, thrombocytopenia, severe leukocytosis, transaminitis, and hyperbilirubinemia. Imaging of the abdomen (ultrasound and magnetic resonance) showed hepatomegaly, splenomegaly, upper limits portal veins diameters, increased thickness of the gallbladder wall, and significant abdominal lymph nodes. Peripheral blood smear and bone marrow evaluation were consistent with acute myeloid leukemia, and liver biopsy showed massive sinusoidal and portal infiltration by leukemic cells. After remission-inducing chemotherapy, there was complete normalization of liver function tests, and liver, spleen, and portal vein size. Conclusions: This case highlights the importance of taking acute myeloid leukemia into account as a possible cause of liver damage to make a rapid diagnosis and start appropriate treatment that may lead to hematological remission and hepatic dysfunction resolution.

Eosinophilic esophagitis (EoE) first-line therapy is represented by budesonide orodispersible tablets (BOT), but a very low number of patients develop oral and esophageal candidiasis. The aim of the study is to evaluate risk factors for the development of oral and esophageal candidiasis during budesonide therapy in EoE patients. A retrospective study was conducted to include all EoE patients in BOT therapy referred to our center. Prevalence, localization, and time of presentation of candidiasis, eosinophilic count in gastroscopy before BOT therapy, and concomitant treatment with proton pump inhibitors (PPI) and its dosage were reviewed. A total of 46 EoE patients in BOT therapy were included in the study. 7 patients (15%) developed oral and/or esophageal candidiasis. 4 patients (57%) of this group were in concomitant PPI therapy, all at 40 mg per day or more dosage, whereas 38% of patients without mycosis were taking this medication (41% at 40 mg per day or more). The mean eosinophil count before treatment was 45/HPF in patients with candidiasis infection and 33/HPF for the others without. Concomitant PPI therapy and high eosinophilic count may represent risk factors in developing mycosis in EoE patients.