Safety and Efficacy of Eucaloric Very Low-Carb Diet (EVLCD) in Type 1 Diabetes: A One-Year Real-Life Retrospective Experience.

A eucaloric very low carbohydrate diet (EVLCD) is a diet with a daily caloric intake equal to the total daily energy expenditure (TDEE) with a carbohydrate content of <50 g/day. The literature on very low carbohydrate diets (VLCD) in type 1 diabetes (DM 1) is limited, although recently published scientific studies have highlighted their safety and efficacy in managing DM 1. In this retrospective analysis, we report the clinical data of 33 patients affected by DM 1 carrying out insulin therapy who switched voluntarily from their usual diet (high carb, low fat) to an EVLCD. Our aim is to evaluate the glycemic control, the amount of insulin needed in order to maintain glycemic control and safety of EVLCD. The switch improved glycemic control (mean glycated hemoglobin decreased from 8.3% to 6.8% (p < 0.01). The number of patients who reached a glycated hemoglobin value of <7% increased statistically from 12% to 57% (p < 0.01), and there was a statistically significant decrease (p < 0.01) in the units of daily insulin (from 36.7± 14.9 IU to 28.9 ±9.1 IU) A reduction from 54% to 24% in clinical level 2 hypoglycemia episodes was reported. No cases of severe hypoglycemia or ketoacidosis were observed. The results of the study support that EVLCD in DM 1 seems safe and effective when adopted under tight medical supervision.

Evaluating pharmacokinetics of bempedoic acid in the treatment of hypercholesterolemia.

Introduction: Bempedoic acid is a first-in-class low-density lipoprotein cholesterol (LDL-C) lowering agent which offers an important opportunity for further LDL-C lowering in statin-intolerant patients or in patients requiring further LDL-C reduction despite maximally tolerated statin therapy.Areas covered: In this review, we examined the pharmacodynamics, pharmacokinetics, clinical efficacy, and safety of bempedoic acid, based on randomized clinical phase III clinical studies and their meta-analyses.Expert opinion: Unlike statins, bempedoic acid is administered as a prodrug and is converted to active form by a liver-specific enzyme. For the liver-specific mechanism of action, bempedoic acid has the potential to reduce the risk of muscle-related adverse events which can limit the utilization and effectiveness of statin therapy.

Stereotactic body radiotherapy vs radiofrequency ablation for the treatment of hepatocellular carcinoma: a meta-analysis.

Background: There are limited and discording results on the comparison between stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). The aim of this meta-analysis was to compare the two treatments in terms of efficacy and safety.Research design and methods: A bibliographic search was performed on main databases through September 2020. Primary outcome was recurrence-free survival. Overall survival and adverse event rates were the secondary outcomes. Results were expressed as odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI)Results: Nine studies enrolling 6545 patients were included. Recurrence-free survival at 1-year was similar between the two treatments (OR 2.11, 0.67-6.63); recurrence-free survival at 2- and 3-year was significantly in favor of SBRT as compared to RFA (OR 2.06, 1.48-2.88 and 1.86, 1.07-3.26, respectively). In a meta-analysis of plotted HRs, SBRT significantly outperformed RFA (HR 0.50, 0.33-0.76, p = 0.001). Overall survival was similar between the two treatments (HR 1.03, 0.72-1.47). No significant difference in terms of severe adverse event rate was observed (OR 1.38, 0.28-6.71).Conclusions: SBRT prolongs recurrence-free survival as compared to RFA in HCC patients, although no significant survival benefit was demonstrated.

Angiotensin Receptor 1 Blockers Prolong Time to Recurrence after Radiofrequency Ablation in Hepatocellular Carcinoma patients: A Retrospective Study.

Inhibition of angiotensin II synthesis seems to decrease hepatocellular carcinoma recurrence after radical therapies; however, data on the adjuvant role of angiotensin II receptor 1 blockers (sartans) are still lacking. Aim of the study was to evaluate whether sartans delay time to recurrence and prolong overall survival in hepatocellular carcinoma patients after radiofrequency ablation. Data on 215 patients were reviewed. The study population was classified into three groups: 113 (52.5%) patients who received neither angiotensin-converting enzyme inhibitors nor sartans (group 1), 59 (27.4%) patients treated with angiotensin-converting enzyme inhibitors (group 2) and 43 (20.1%) patients treated with sartans (group 3). Survival outcomes were analyzed using Kaplan-Meier analysis and compared with log-rank test. In the whole study population, 85.6% of patients were in Child-Pugh A-class and 89.6% in Barcelona Clinic Liver Cancer A stage. Median maximum tumor diameter was 30 mm (10-40 mm) and alpha-fetoprotein was 25 (1.1-2100) IU/mL. No differences in baseline characteristics among the three groups were reported. Median overall survival was 48 months (42-51) in group 1, 51 months (42-88) in group 2, and 63 months (51-84) in group 3 (p = 0.15). Child-Pugh stage and Model for End-staging Liver Disease (MELD) score resulted as significant predictors of overall survival in multivariate analysis. Median time to recurrence was 33 months (24-35) in group 1, 41 (23-72) in group 2 and 51 months (42-88) in group 3 (p = 0.001). Number of nodules and anti-angiotensin treatment were confirmed as significant predictors of time to recurrence in multivariate analysis. Sartans significantly improved time to recurrence after radiofrequency ablation in hepatocellular carcinoma patients but did not improve overall survival.

Comparison between Y90 Radioembolization Plus Sorafenib and Y90 Radioembolization alone in the Treatment of Hepatocellular Carcinoma: A Propensity Score Analysis.

BACKGROUND: Adjuvant sorafenib may enhance the efficacy of transarterial radioembolization with yttrium-90 in hepatocellular carcinoma patients. The aim of this study is to assess the efficacy and safety of radioembolization plus sorafenib in comparison to radioembolization alone. METHODS: Out of 175 hepatocellular carcinoma (HCC) patients treated with radioembolization between 2011 and 2018, after propensity score matching, two groups were compared: a group of 45 patients that underwent radioembolization while being on sorafenib (Group 1) and a second group of 90 patients that underwent radioembolization alone (Group 2). RESULTS: Baseline characteristics of the two groups were well balanced concerning liver function and tumor burden. No significant differences in survival outcomes were identified (median overall survival 10 vs. 10 months; p = 0.711), median progression-free survival 6 vs. 7 months (p = 0.992) in Group 1 and Group 2). The objective response rate in Group 1 vs. Group 2 was 45.5% vs. 42.8% (p = 1) according to mRECIST. No differences in toxicity nor in liver decompensation rates were registered. CONCLUSIONS: The association of sorafenib does not prolong survival nor delay progression in patients treated with radioembolization. Liver toxicity does not differ among the two therapeutic schemes.

Adiponectin and Orexin-A as a Potential Immunity Link Between Adipose Tissue and Central Nervous System.

Adipose tissue (AT) is strongly associated with development and progression of immune disorders through adipokines secretion, such as adiponectin. This protein has beneficial energetic properties and is involved in inflammation and immunity processes. Three oligomers of circulating adiponectin with different molecular weight are described: High (HMW), Medium (MMW), and Low (LMW). The HMW is the most biologically active oligomers. On binding to its receptors AdipoR1, AdipoR2, and T-cadherin, adiponectin acts on both innate and acquired immunity. The suppression of NF-κB activation and pro-inflammatory cytokine expression in macrophages is mediated by AdipoR1. AdipoR2 mediates polarization of anti-inflammatory M2 macrophages T-cadherin is essential for the M2 macrophage proliferation. Furthermore, adiponectin reduces T cells responsiveness and B cells lymphopoiesis. The immune system is very sensitive to environmental changes and it is not only interconnected with AT but also with the central nervous system (CNS). Cytokines, which are mediators of the immune system, exercise control over mediators of the CNS. Microglia, which are immunity cells belonging to the macrophage family, are present within the CNS. The nervous system is also involved in immunity through the production of neuropeptides such as orexin-A/hypocretin-1. This neuropeptide is involved in metabolic disorders, inflammation and in the immune response. The relationship between adipokines, immunity, and the nervous system is validated by both the role of orexin-A on fat, food intake, and energy expenditure, as well as by role of adiponectin on the CNS. In this review, we focused on the functions of adiponectin and orexin-A as a potential immunity link between AT and CNS.