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.

Background: Several prognostic models have been developed to stage hepatocellular carcinoma (HCC) but there is no general consensus on which is the most reliable. We compared three prognostic indices (Okuda, CLIP, and BCLC scoring systems) in a large series of cirrhotic patients with HCC undergoing non-surgical treatment in terms of their ability to classify patients into different risk groups Methods: We retrospectively studied 268 Italian patients with HCC. A total of 146 patients were treated with ablation, 132 with percutaneous ethanol injection, and 14 with radiofrequency ablation; 103 underwent transcatheter arterial chemoembolisation and 19 had supportive care alone. Factors determining survival were analysed by univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard regression models. Okuda, CLIP, and BCLC scores evaluated before treatment were applied. Results: Median survival was 25.7 months. In a multivariate analysis, portal vein thrombosis, α fetoprotein, total bilirubin, and tumour size were significant predictors of survival. Okuda, CLIP, and BCLC scores were all able to predict survival (p<0.001). They identified two, four, and six risk groups, respectively, with a median survival ranging from 27 to 19 months for Okuda, 30 to 5 months for CLIP, and 43 to 7 months for BCLC. Conclusions: Both CLIP and BCLC scores were more effective than the Okuda score in stratifying patients into different risk groups with early-intermediate HCC. However, the BCLC scoring system gave a better prediction of prognosis in patients with disease diagnosis at a very early stage.

Aims of this retrospective study were to analyze the efficacy and safety of percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) in cirrhotic patients with hepatocellular carcinoma (HCC) submitted to orthotopic liver transplantation (OLT). We studied 40 patients undergoing OLT in whom 46 HCC nodules had been treated with PEI (13 nodules), RFA (30 nodules), or PEI+RFA (3 nodules). Child-Turcotte-Pugh class was A in 18 cases, B in 18, and C in 4. The mean waiting time for OLT was 9.5 months. The effectiveness of ablation techniques was evaluated by histological examination of the explanted livers. Complete necrosis was found in 19 nodules (41.3%), partial or absent necrosis in 27 nodules (58.7%). Among the 30 nodules treated by RFA, 14 were completely necrotic (46.7%) and 16 demonstrated partial necrosis (53.3%). Considering the 13 neoplasms undergoing PEI, 3 nodules showed complete necrosis (23.1%), 6 partial necrosis (46.1%), and 4 absent necrosis (30.8%). The rate of complete necrosis was 53.1% for nodules smaller than 3 cm and 14.3% for larger lesions ( P = 0.033) but increased to 61.9% when considering only the lesions smaller than 3 cm treated by RFA. During the follow up, HCC recurred in 3 patients treated by PEI. No cases of HCC recurrence at the abdominal wall level were recorded. Percutaneous ablation procedures are effective treatments in cirrhotic patients with HCC submitted to OLT and are not associated to an increased risk of tumor recurrence. RFA provides complete necrosis in most nodules smaller than 3 cm, and appears to be the best treatment option in these cases.

Aim: The aim of the present study was to describe the clinical presentation of patients aged ≥80 years with coronavirus disease 2019 (COVID‐19), and provide insights regarding the prognostic factors and the risk stratification in this population.Methods: This was a single‐center, retrospective, observational study, carried out in a referral center for COVID‐19 in central Italy. We reviewed the clinical records of patients consecutively admitted for confirmed COVID‐19 over a 1‐month period (1–31 March 2020). We excluded asymptomatic discharged patients. We identified risk factors for death, by a uni‐ and multivariate Cox regression analysis. To improve model fitting and hazard estimation, continuous parameters where dichotomized by using Youden’s index.Results: Overall, 69 patients, aged 80–98 years, met the inclusion criteria and were included in the study cohort. The median age was 84 years (82–89 years is interquartile range); 37 patients (53.6%) were men. Globally, 14 patients (20.3%) presented a mild, 30 (43.5%) a severe and 25 (36.2%) a critical COVID‐19 disease. A total of 23 (33.3%) patients had died at 30 days’ follow up. Multivariate Cox regression analysis showed that severe dementia, pO₂ ≤90 at admission and lactate dehydrogenase >464 U/L were independent risk factors for death.Conclusions: The present data suggest that risk of death could be not age dependent in patients aged ≥80 years, whereas severe dementia emerged is a relevant risk factor in this population. Severe COVID‐19, as expressed by elevated lactate dehydrogenase and low oxygen saturation at emergency department admission, is associated with a rapid progression to death in these patients. Geriatr Gerontol Int 2020; ••: ••–••.

Climate change is widely recognized as one of the most significant challenges facing our planet and human civilization. Human activities such as the burning of fossil fuels, deforestation, and industrial processes release greenhouse gases into the atmosphere, leading to a warming of the Earth’s climate. The relationship between climate change and cardiovascular (CV) health, mediated by air pollution and increased ambient temperatures, is complex and very heterogeneous. The main mechanisms underlying the pathogenesis of CV disease at extreme temperatures involve several regulatory pathways, including temperature-sympathetic reactivity, the cold-activated renin-angiotensin system, dehydration, extreme temperature-induced electrolyte imbalances, and heat stroke-induced systemic inflammatory responses. The interplay of these mechanisms may vary based on individual factors, environmental conditions, and an overall health background. The net outcome is a significant increase in CV mortality and a higher incidence of hypertension, type II diabetes mellitus, acute myocardial infarction (AMI), heart failure, and cardiac arrhythmias. Patients with pre-existing CV disorders may be more vulnerable to the effects of global warming and extreme temperatures. There is an urgent need for a comprehensive intervention that spans from the individual level to a systemic or global approach to effectively address this existential problem. Future programs aimed at reducing CV and environmental burdens should require cross-disciplinary collaboration involving physicians, researchers, public health workers, political scientists, legislators, and national leaders to mitigate the effects of climate change.