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The article discusses Italy has one of the highest 2019 coronavirus disease clinical burdens in the world, with an average of 4,000 new diagnoses per day and a daily increase above 19%. Topics include the floor designated to host the unit has rushed to completion, allowing the first patient admission within three working days; and the main fields of expertise included internal and emergency medicine, pneumology, and surgery.

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.

Hepatocellular carcinomas (HCCs) are highly heterogeneous malignancies. They are characterized by a peculiar tumor microenvironment and dense vascularization. The importance of signaling between immune cells, endothelial cells, and tumor cells leads to the difficult recapitulation of a reliable in vitro HCC model using the conventional two-dimensional cell cultures. The advent of three-dimensional organoid tumor technology has revolutionized our understanding of the pathogenesis and progression of several malignancies by faithfully replicating the original cancer genomic, epigenomic, and microenvironmental landscape. Organoids more closely mimic the in vivo environment and cell interactions, replicating factors such as the spatial organization of cell surface receptors and gene expression, and will probably become an important tool in the choice of therapies and the evaluation of tumor response to treatments. This review aimed to describe the ongoing and potential applications of organoids as an in vitro model for the study of HCC development, its interaction with the host's immunity, the analysis of drug sensitivity tests, and the current limits in this field.

Vaccines prevent a significant number of deaths annually. However, certain populations do not respond adequately to vaccination due to impaired immune systems. Cirrhosis, a condition marked by a profound disruption of immunity, impairs the normal immunization process. Critical vaccines for cirrhotic patients, such as the hepatitis A virus (HAV), hepatitis B virus (HBV), influenza, pneumococcal, and coronavirus disease 19 (COVID-19), often elicit suboptimal responses in these individuals. The humoral response, essential for immunization, is less effective in cirrhosis due to a decline in B memory cells and an increase in plasma blasts, which interfere with the creation of a long-lasting response to antigen vaccination. Additionally, some T cell subtypes exhibit reduced activation in cirrhosis. Nonetheless, the persistence of memory T cell activity, while not preventing infections, may help to attenuate the severity of diseases in these patients. Alongside that, the impairment of innate immunity, particularly in dendritic cells (DCs), prevents the normal priming of adaptive immunity, interrupting the immunization process at its onset. Furthermore, cirrhosis disrupts the gut-liver axis balance, causing dysbiosis, reduced production of short-chain fatty acids (SCFAs), increased intestinal permeability, and bacterial translocation. Undermining the physiological activity of the immune system, these alterations could impact the vaccine response. Enhancing the understanding of the molecular and cellular factors contributing to impaired vaccination responses in cirrhotic patients is crucial for improving vaccine efficacy in this population and developing better prevention strategies.

Acute pancreatitis is a complex inflammatory disease with significant morbidity and mortality. Despite advances in its management, the role of antibiotics in the prophylaxis and treatment of acute pancreatitis remains controversial. The aim of this comprehensive review is to analyze current evidence on the use of antibiotics in acute pancreatitis, focusing on prophylactic and therapeutic strategies. Prophylactic use aims to prevent local and systemic infections. However, recent studies have questioned the routine use of antibiotics for prophylaxis and highlighted the potential risks of antibiotic resistance and adverse effects. In selected high-risk cases, such as infected necrotizing pancreatitis, prophylactic antibiotic therapy may still be beneficial. As for therapeutic use, antibiotics are usually used to treat infected pancreatic necrosis and extrapancreatic infections. When selecting an antibiotic, the microbiologic profile and local resistance patterns should be considered. Combination therapy with broad-spectrum antibiotics is often recommended to cover both Gram-positive and Gram-negative pathogens. Recent research has highlighted the importance of individualized approaches to antibiotic use in acute pancreatitis and underscored the need for a tailored approach based on patient-specific factors. This review also highlights the potential role of new antimicrobial agents and alternative strategies, such as probiotics, in the management of acute pancreatitis.

Fibrosis is an unavoidable consequence of chronic inflammation. Extracellular matrix deposition by fibroblasts, stimulated by multiple pathways, is the first step in the onset of chronic liver disease, and its propagation promotes liver dysfunction. At the same time, chronic liver disease is characterized by alterations in primary and secondary hemostasis but unlike previously thought, these changes are not associated with an increased risk of bleeding complications. In recent years, the role of coagulation imbalance has been postulated as one of the main mechanisms promoting hepatic fibrogenesis. In this review, we aim to investigate the function of microvascular thrombosis in the progression of liver disease and highlight the molecular and cellular networks linking hemostasis to fibrosis in this context. We analyze the predictive and prognostic role of coagulation products as biomarkers of liver decompensation (ascites, variceal hemorrhage, and hepatic encephalopathy) and liver-related mortality. Finally, we evaluate the current evidence on the application of antiplatelet and anticoagulant therapies for prophylaxis of hepatic decompensation or prevention of the progression of liver fibrosis.

The human gut is inhabited by a multitude of bacteria, yeasts, and viruses. A dynamic balance among these microorganisms is associated with the well-being of the human being, and a large body of evidence supports a role of dysbiosis in the pathogenesis of several diseases. Given the importance of the gut microbiota in the preservation of human health, probiotics, prebiotics, synbiotics, and postbiotics have been classically used as strategies to modulate the gut microbiota and achieve beneficial effects for the host. Nonetheless, several molecules not typically included in these categories have demonstrated a role in restoring the equilibrium among the components of the gut microbiota. Among these, rifaximin, as well as other antimicrobial drugs, such as triclosan, or natural compounds (including evodiamine and polyphenols) have common pleiotropic characteristics. On one hand, they suppress the growth of dangerous bacteria while promoting beneficial bacteria in the gut microbiota. On the other hand, they contribute to the regulation of the immune response in the case of dysbiosis by directly influencing the immune system and epithelial cells or by inducing the gut bacteria to produce immune-modulatory compounds, such as short-chain fatty acids. Fecal microbiota transplantation (FMT) has also been investigated as a procedure to restore the equilibrium of the gut microbiota and has shown benefits in many diseases, including inflammatory bowel disease, chronic liver disorders, and extraintestinal autoimmune conditions. One of the most significant limits of the current techniques used to modulate the gut microbiota is the lack of tools that can precisely modulate specific members of complex microbial communities. Novel approaches, including the use of engineered probiotic bacteria or bacteriophage-based therapy, have recently appeared as promising strategies to provide targeted and tailored therapeutic modulation of the gut microbiota, but their role in clinical practice has yet to be clarified. The aim of this review is to discuss the most recently introduced innovations in the field of therapeutic microbiome modulation.

Liver cirrhosis is a chronic disease that can be complicated by episodes of decompensation such as variceal bleeding, hepatic encephalopathy, ascites, and jaundice, with subsequent increased mortality. Infections are also among the most common complications in cirrhotic patients, mostly due to a defect in immunosurveillance. Among them, one of the most frequent is spontaneous bacterial peritonitis (SBP), defined as the primary infection of ascitic fluid without other abdominal foci. SBP is mainly induced by Gram-negative bacteria living in the intestinal tract, and translocating through the intestinal barrier, which in cirrhotic patients is defective and more permeable. Moreover, in cirrhotic patients, the intestinal microbiota shows an altered composition, poor in beneficial elements and enriched in potentially pathogenic ones. This condition further promotes the development of leaky gut and increases the risk of SBP. The first-line treatment of SBP is antibiotic therapy; however, the antibiotics used have a broad spectrum of action and may adversely affect the composition of the gut microbiota, worsening dysbiosis. For this reason, the future goal is to use new therapeutic agents that act primarily on the gut microbiota, selectively modulating it, or on the intestinal barrier, reducing its permeability. In this review, we aim to describe the reciprocal relationship between gut microbiota and SBP, focusing on pathogenetic aspects but also on new future therapies.

The understanding of the host immune response to SARS-CoV-2 variants of concern is critical for improving diagnostics, therapy development, and vaccines. Here, we analyzed the level of neutralizing antibodies against SARS-CoV-2 D614G, Delta, Gamma, Mu, and Omicron variants in D614G infected healthcare workers during a follow-up up to 6 months after recovery. We followed up 76 patients: 60.5% were women and 39.5% men. The 96.1% and 3.9% were symptomatic and asymptomatic, respectively. The most frequent symptoms were headache, myalgia, and cough. The 65.8%, 65.8%, and 92.1% of the infected individuals were positive for neutralizing antibodies against D614G variant at 2, 4, and 6 months of follow-up, respectively. The 26.3%, 48.7% and 65.8% of patients neutralized Delta variant, 19.7%, 32.9% and 52.6% of patients neutralized Gamma, 7.9%, 19.7% and 44.7% of patients neutralized Mu, and 4.0%, 9.2% and 15.8% of patients neutralized Omicron. Low neutralization against Gamma and Mu variants was observed during the follow-up, and very low against the Omicron variant was detected during the same period. The median of neutralizing antibody titers against D614G and Delta variants increased significantly during the follow-up. An association was observed between the levels of neutralizing antibodies against D614G and Delta variants and the severity of the disease. Our results suggest an immune escape from neutralizing antibodies with the Omicron variant because of the many mutations localized in the S protein., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

About one-fourth of adults globally suffer from nonalcoholic fatty liver disease (NAFLD), which is becoming a leading cause of chronic liver disease worldwide. Its prevalence has rapidly increased in recent years, and is projected to increase even more. NAFLD is a leading cause of hepatocellular carcinoma (HCC), the sixth-most prevalent cancer worldwide and the fourth most common cause of cancer-related death. Although the molecular basis of HCC onset in NAFLD is not completely known, inflammation is a key player. The tumor microenvironment (TME) is heterogeneous in patients with HCC, and is characterized by complex interactions between immune system cells, tumor cells and other stromal and resident liver cells. The etiology of liver disease plays a role in controlling the TME and modulating the immune response. Markers of immune suppression in the TME are associated with a poor prognosis in several solid tumors. Immunotherapy with immune checkpoint inhibitors (ICIs) has become the main option for treating cancers, including HCC. However, meta-analyses have shown that patients with NAFLD-related HCC are less likely to benefit from therapy based on ICIs alone. Conversely, the addition of an angiogenesis inhibitor showed better results regarding the objective response rate and progression-free survival. Adjunctive diagnostic and therapeutic strategies, such as the application of novel biomarkers and the modulation of gut microbiota, should be considered in the future to guide personalized medicine and improve the response to ICIs in patients with NAFLD-related HCC., Competing Interests: Conflict-of-interest statement: The authors have no conflict of interest to declare., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Asymptomatic SARS-CoV-2 infection of healthcare workers (HCWs) has been reported as a key player in the nosocomial spreading of COVID-19. Early detection of infected HCWs can prevent spreading of the virus in hospitals among HCWs and patients. We conducted a cross-sectional study to determine the asymptomatic infection of HCWs in a private clinic in the city of Santiago, Chile. Our study was conducted during a period of 5 weeks at the peak of transmission of SARS-CoV-2 in Chile. Nasopharyngeal samples were obtained from 413 HCWs and tested for the presence of SARS-CoV-2 using RT-qPCR. We found that a 3.14% of HCWs were positive for the presence of SARS-CoV-2 (14/413). Out of these, 7/14 were completely asymptomatic and did not develop symptoms within 3 weeks of testing. Sequencing of viral genomes showed the predominance of the GR clade; however, sequence comparison demonstrated numerous genetic differences among them suggesting community infection as the main focus of transmission among HCWs. Our study demonstrates that the protocols applied to protect HCWs and patients have been effective as no infection clusters due to asymptomatic carriers were found in the clinic. Together, these data suggest that infection with SARS-CoV-2 among HCWs of this health center is not nosocomial., Competing Interests: The authors have declared that no competing interests exist

The Madigan Endoscopic Sinus Surgery (ESS) Simulator, developed by a multi-institution team led by Lockheed Martin, includes force-feedback instrument and virtual endoscope interaction with three-dimensional paranasal anatomy models derived from the Visible Human dataset, supplemented by a variety of graphical and auditory instructional aids embedded in the model. Our formal evaluation of Version 1.2 of the system focused on its validity as an ESS simulator. Run-time and survey data were collected for three groups of subjects on a common protocol progressing through the three basic ESS subtasks: navigation, injection, and dissection. Non-MD subjects performed the tasks on a simplified abstract virtual model with instructional aids (hoops for the navigation path, injection targets, dissection spheres, auditory feedback about task completion, and simulated patient heart rhythm). Non-ENT MDs progressed from this "novice" model to a simulated anterior ethmoidectomy on an "intermediate" model with the aids embedded in the reconstructed and segmented paranasal anatomy. Otolaryngologists ranging from second-year ENT residents through senior staff progressed through both the abstract and intermediate models, and then performed the simulated surgical procedure on an "advanced" model, consisting of the anatomy with no instructional aids. The procedural validity of the simulator is supported by a strong correlation between performance on the simulator and degree of prior ESS experience, by convergent correlation among independent measures of subject task performance, and by subjective evaluations by experienced ESS surgeons.