Explore the vast range of titles available.

Lipopolysaccharides (LPSs) are bacterial surface glycolipids, produced by Gram-negative bacteria. LPS is known to determine acute inflammatory reactions, particularly in the context of sepsis. However, LPS can also trigger chronic inflammation. In this case, the source of LPS is not an external infection, but rather an increase in endogenous production, which is usually sustained by gut microbiota (GM), and LPS contained in food. The first site in which LPS can exert its inflammatory action is the gut: both GM and gut-associated lymphoid tissue (GALT) are influenced by LPS and shift towards an inflammatory pattern. The changes in GM and GALT induced by LPS are quite similar to the ones seen in IBD: GM loses diversity, while GALT T regulatory (Tregs) lymphocytes are reduced in number, with an increase in Th17 and Th1 lymphocytes. Additionally, the innate immune system is triggered, through the activation of toll-like receptor (TLR)-4, while the epithelium is directly damaged, further triggering inflammation. In this review, we will discuss the importance of the crosstalk between LPS, GM, and GALT, and discuss the possible implications.

The Special Issue titled “Editorial Board Members’ Collection Series: Gastrointestinal and Hepatic Diseases” is a collection of papers from our Editorial Board Members and researchers invited by them [...]

It has been proposed that vaccines may exert an unspecific protective effect against infectious agents, different than expected. Coronavirus disease 2019 (COVID-19) is a pandemic infection with high mortality in older patients due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The high number of vaccinations may be one of the reasons why children show a lower susceptibility to SARS-CoV-2 infection and milder severity when compared to adults. We have designed a study aimed at investigating whether the influenza vaccine may reduce the susceptibility and severity of SARS-CoV-2 infection. We retrospectively enrolled 635 patients who accessed our Emergency Department from March 1st to June 30th, 2020, and were diagnosed with COVID-19 infection confirmed by an RT-PCR on an oropharyngeal swab. Clinical data, outcomes, and influenza vaccination status were collected from the electronic medical records of our Hospital. We also used data from the Italian Health Ministry to compare the prevalence of flu vaccination among the general population of the Lazio Region and our enrolled patients. We then compared clinical outcomes between vaccinated and non-vaccinated patients, by univariate and multivariate analysis. COVID-19-positive patients older than 65 years reported a lower prevalence of flu vaccination when compared to the general population residing in the Lazio (p = 0.004). After correction for gender, age, and comorbidities, we found a lower risk of death at 60 days in patients with flu vaccination than in not vaccinated patients (p = 0.001). Our study shows that flu vaccination could reduce the mortality of COVID-19. Prospective studies are needed to confirm this result.

Background and objectives: the emergency department (ED) is frequently identified by patients as a possible solution for all healthcare problems, leading to a high rate of misuse of the ED, possibly causing overcrowding. The coronavirus disease 2019 (COVID-19) pandemic started in China; it then spread throughout Italy, with the first cases confirmed in Lombardy, Italy, in February 2020. This has totally changed the type of patients referred to EDs. The aim of this study was to analyze the reduction of ED admissions at a Second level urban teaching (Fondazione Policlinico Universitario Agostino Gemelli IRCCS) during the COVID-19 pandemic. Materials and Methods: in this retrospective observational cross-sectional study, we reviewed and compared clinical records of all the patients consecutively admitted to our ED over a 40-day period (21 February –31 March) in the last three years (2018–2019–2020). Mean age, sex, triage urgency level, day/night admission, main presentation symptom, and final diagnosis, according to different medical specialties, hospitalization, and discharge rate, were analyzed. Results: we analyzed 16,281 patient clinical records. The overall reduction in ED admissions in 2020 was 37.6% compared to 2019. In 2020, we observed an increase in triage urgency levels for ED admissions (the main presentation symptom was a fever). We noticed a significant drop in admissions for cardio-thoracic, gastroenterological, urological, otolaryngologic/ophthalmologic, and traumatological diseases. Acute neurological conditions registered only a slight, but significant, reduction. Oncology admissions were stable. Admissions for infectious diseases were 30% in 2020, compared to 5% and 6% in 2018 and 2019, respectively. In 2020, the hospitalization rate increased to 42.9% compared to 27.7%, and 26.4% in previous years. Conclusions: the drastic reduction of ED admissions during the pandemic may be associated with fear of the virus, suggesting that patients with serious illnesses did not go to the emergency room. Moreover, there was possible misuse of the ED in the previous year. In particular, worrisome data emerged regarding a drop in cardiology and neurology admissions. Those patients postponed medical attention, possibly with fatal consequences, just for fear of exposure to COVID-19, leading to unnecessary morbidity and mortality.

Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, frequently resulting in septic shock and multi-organ failure. Emerging evidence highlights the critical role of neutrophil extracellular traps (NETs) in the pathophysiology of sepsis. NETs are extracellular structures composed of chromatin DNA, histones, and granular proteins released by neutrophils through a specialized form of cell death known as NETosis. While NETs contribute to the containment of pathogens, their excessive or dysregulated production in sepsis is associated with endothelial damage, immunothrombosis, and organ dysfunction. Several NET-associated biomarkers have been identified, including circulating cell-free DNA (cfDNA), histones, MPO-DNA complexes, and neutrophil elastase–DNA complexes, which correlate with the disease severity and prognosis. Therapeutic strategies targeting NETs are currently under investigation. Inhibition of NET formation using PAD4 inhibitors or ROS scavengers has shown protective effects in preclinical models. Conversely, DNase I therapy facilitates the degradation of extracellular DNA, reducing the NET-related cytotoxicity and thrombotic potential. Additionally, heparin and its derivatives have demonstrated the ability to neutralize NET-associated histones and mitigate coagulopathy. Novel approaches include targeting upstream signaling pathways, such as TLR9 and IL-8/CXCR2, offering further therapeutic promise.

Background/Objectives: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome, often referred to as PFAPA syndrome, may enigmatically recur for an undetermined time in affected children: a potential reason to explain its recurring pattern for an unpredictable period or its self-limitation is currently unknown. We explored the relationship between different general, demographic, clinical, and laboratory features of PFAPA children and disease evolution over the course of a decade. Methods: We have retrospectively screened 150 Italian children with a history of PFAPA syndrome attending the Outpatients Clinic of Pediatric Rheumatology in our Institution during the period 2014–2024, all without any recognized chronic diseases: 88 males, 62 females, mean age at onset of 2.5 ± 1.7 years, age range of 0.3–9.4 years, and mean age at diagnosis of 4.5 ± 2.0 years. The whole cohort of PFAPA patients had been followed up for a median period of 5 years (IQR: 4–7). Results and Conclusions: After dividing patients into two groups based on either the disappearance or persistence of PFAPA symptoms during follow-up, we found that positive family history of recurring fevers, cervical lymphadenopathy, arthralgia, myalgia, and breastfeeding for more than 6 months were associated with the disappearance of febrile attacks for at least six months. Performing a multivariate analysis adjusted for sex and age, we found that only breastfeeding duration longer than 6 months and higher education level of PFAPA patients’ mothers were independently associated with the resolution of PFAPA symptoms.

Digestive diseases are a rapidly evolving area of clinical and research [...]

Background and Objectives: Shift work and night work are common among emergency physicians. It is necessary to provide continuous care to patients, especially with acute diseases, including throughout the night. Literature studies show that shift and night workers have an altered light exposure, timing of sleep and intake of food. The consequence of this desynchronization with the biological clock can lead these workers to be more exposed to developing some acute and chronic health conditions. In particular, the alteration of the sleep–wake cycle, fatigue, the shortened sleep duration and the misalignment of the body’s hormone production is a codified risk factor of gut dysbiosis that can lead to acute and chronic diseases, also gastrointestinal ones. the aim of this narrative review is to collect and summarize evidence about the association between the disruption of the circadian rhythm, sleep and food timing alterations, gut dysbiosis and the risk of gastrointestinal diseases among shift and night workers. Materials and Methods: we searched for evidence about the association of shift and night work, dysbiosis, gut microbiota and gastrointestinal diseases among shift workers in healthcare settings. Results: shift work and night work are associated with a higher risk of diseases, an inflammatory state and the alteration of the gut microbiota composition; but definitive data are still inconsistent. Conclusions: Until now, obtaining conclusive results in regard to the relationship between shift work, the gut microbiota and the increased risk of gastrointestinal disorders has been particularly complex and not yet feasible. More confirmatory studies are needed to better characterize risk factors and realize preventive measures.

Background: Many literature studies have reported the beneficial effects of probiotics on human health, but few articles have evaluated their “real effects” on the modulation of microbiota after their use. Lactobacillus reuteri (L. reuteri) is one of the most studied probiotics with the best effects on gut microbiota. Aims: The primary aim of our study was the evaluation of the intestinal colonization by L. reuteri-LMG P 27481 and its effects on the modification of the gut bacterial flora. The secondary aim was the evaluation of side effects through the validated Gastrointestinal Symptom Rating Scale (GSRS). Patients and Methods: This is an interventional, open-label study conducted on 20 healthy adults (10 men and 10 women M/F; mean age 34 ±15 years) who received a probiotic Reuterin® LMG (L. reuteri LMG P 27481) for 28 consecutive days in drops at a concentration of 1 × 109 (five drops per day). Microbiota analysis was performed at enrollment (T0), at the end of probiotic supplementation (T1) and after a 14-day follow-up period (T2). Results: In our study we observed interesting quantitative and functional variations as regards the Firmicutes/Bacterioidetes ratio, intestinal permeability, and the production of short-chain fatty acids (SCFA). This probiotic was safe and was able to improve patients’ symptoms. Conclusions: The intake of L. reuteri LMG-P 27481 in healthy subjects showed transitory variations in some functional and metabolic gut functions, especially an improvement in the barrier effect and intestinal permeability, y and an increase in SCFA. Future studies should include target populations to have a greater range for modulation of the gut microbiota.

Pancreatic cystic lesions are increasingly detected in cross-sectional imaging. Intraductal papillary mucinous neoplasm (IPMN) is a mucin-producing subtype of the pancreatic cyst lesions arising from the pancreatic duct system. IPMN is a potential precursor of pancreatic cancer. The transformation of IPMN in pancreatic cancer is progressive and requires the occurrence of low-grade dysplasia, high-grade dysplasia, and ultimately invasive cancer. Jaundice, enhancing mural nodule >5 mm, main pancreatic duct diameter >10 mm, and positive cytology for high-grade dysplasia are considered high-risk stigmata of malignancy. While increased levels of carbohydrate antigen 19-9 (CA 19-9) (>37 U/mL), main pancreatic duct diameter 5–9.9 mm, cyst diameter >40 mm, enhancing mural nodules <5 mm, IPMN-induced acute pancreatitis, new onset of diabetes, cyst grow-rate >5 mm/year are considered worrisome features of malignancy. However, cross-sectional imaging is often inadequate in the prediction of high-grade dysplasia and invasive cancer. Several studies evaluated the role of humoral and intra-cystic biomarkers in the prediction of malignancy in IPMN. Carcinoembryonic antigen (CEA), CA 19-9, intra-cystic CEA, intra-cystic glucose, and cystic fluid cytology are widely used in clinical practice to distinguish between mucinous and non-mucinous cysts and to predict the presence of invasive cancer. Other biomarkers such as cystic fluid DNA sequencing, microRNA (mi-RNA), circulating microvesicles, and liquid biopsy are the new options for the mini-invasive diagnosis of degenerated IPMN. The aim of this study is to review the literature to assess the role of humoral and intracystic biomarkers in the prediction of advanced IPMN with high-grade dysplasia or invasive carcinoma.