Prevalence and Management of Complications of Percutaneous Ethanol Injection for Cystic Thyroid Nodules: A Systematic Review of Literature and Meta-analysis.

Background: We assessed the prevalence of complications from percutaneous ethanol injection (PEI) for benign and cystic thyroid nodules (CTNs) and their management. Methods: We conducted a systematic review with meta-analysis of data from published observational studies on PEI of CTNs. We also included unpublished retrospectively collected data on complications after PEI from all consecutive patients with cytologically benign CTNs who underwent PEI at the Unit of Endocrinology and Metabolic Diseases, AOU University of Campania Luigi Vanvitelli (Naples, Italy) between June 1, 2021, and March 31, 2024. A random effects meta-analysis was performed on the prevalence rate data. Pooled prevalence data were presented with confidence intervals (CIs). The I2 statistic index was used to quantify the heterogeneity. The details of the complications and the management were qualitatively described. Results: The literature search yielded 1189 studies, of which 48 studies were included in the systematic review and meta-analysis, in addition to our institutional experience (3670 CTNs in total). The overall quality of each included study was judged as fair. The prevalence of "Overall" complications of PEI was 32% ([CI 25-40%], I2 92.7%, 967 of 3195 thyroid nodules [TNs]). The prevalence of "Minor" complications of PEI was 32% ([CI 25-40%], I2 92.7%, 952 of 3195 TNs). The prevalence of "Major" complications of PEI was 2% ([CI 1-2%], I2 0%, 22 of 3670 TNs). Sensitivity analyses did not modify the results. The pooled prevalence rate of local pain was 21% (CI [16-27] I2 90.3). Local pain was typically transient and mild, sometimes moderate, and requiring analgesics for few days. The pooled prevalence rate of dysphonia was 1% (CI [1-2], I2 0). Dysphonia was transient and could last from several hours to 12 months after PEI. Conclusions: Complications of PEI for benign and CTNs are relatively common, but most are minor and usually transient, not requiring treatment. Dysphonia was a major complication, but it was uncommon and transient. PEI for CTNs could be considered a generally safe technique.

Cardiometabolic risk factors in MASLD patients with HCC: the other side of the coin.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) constitutes the commonest cause of chronic liver disorder worldwide, whereby affecting around one third of the global population. This clinical condition may evolve into Metabolic Dysfunction-Associated Steatohepatitis (MASH), fibrosis, cirrhosis and hepatocellular carcinoma (HCC), in a predisposed subgroup of patients. The complex pathogenesis of MASLD is severely entangled with obesity, dyslipidemia and type 2 diabetes (T2D), so far so nutritional and lifestyle recommendations may be crucial in influencing the risk of HCC and modifying its prognosis. However, the causative association between HCC onset and the presence of metabolic comorbidities is not completely clarified. Therefore, the present review aimed to summarize the main literature findings that correlate the presence of inherited or acquired hyperlipidemia and metabolic risk factors with the increased predisposition towards liver cancer in MASLD patients. Here, we gathered the evidence underlining the relationship between circulating/hepatic lipids, cardiovascular events, metabolic comorbidities and hepatocarcinogenesis. In addition, we reported previous studies supporting the impact of triglyceride and/or cholesterol accumulation in generating aberrancies in the intracellular membranes of organelles, oxidative stress, ATP depletion and hepatocyte degeneration, influencing the risk of HCC and its response to therapeutic approaches. Finally, our pursuit was to emphasize the link between HCC and the presence of cardiometabolic abnormalities in our large cohort of histologically-characterized patients affected by MASLD (n=1538), of whom 86 had MASLD-HCC by including unpublished data.

Liraglutide for Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease: The STARDUST Randomized Clinical Trial.

Importance: Peripheral artery disease (PAD) in diabetes may lead to diabetic foot ulcer and lower-extremities amputation. Glucagon-like peptide 1 receptor agonists have proven cardiovascular benefits in trials of people with type 2 diabetes at high cardiovascular risk. Objective: To examine the effect of liraglutide on peripheral perfusion measured as peripheral transcutaneous oxygen pressure (TcPo2) in individuals with type 2 diabetes and PAD. Design, Setting, and Participants: This open-label randomized clinical trial was conducted between February 1, 2021, and June 30, 2022, with a final follow-up on December 30, 2022, at University of Campania "Luigi Vanvitelli," Naples, Italy. Fifty-five individuals with type 2 diabetes, PAD, and TcPo2 between 30 and 49 mm Hg were included. Interventions: Patients were randomized to receive 1.8 mg of subcutaneous liraglutide or conventional treatment of cardiovascular risk factors (control group) for 6 months. Main Outcomes and Measures: Coprimary outcomes were the change from baseline of peripheral perfusion between groups and the comparison of the proportion of individuals who reached 10% increase of TcPo2 from baseline in each group. Results: Fifty-five participants (mean [SD] age, 67.5 [8.5] years; 43 [78%] male) were randomized (27 to the liraglutide group and 28 to the control group) and analyzed. Participants had a median (IQR) hemoglobin A1c level of 6.9% (6.5%-7.8%) and a mean (SD) TcPo2 of 40.3 (5.7) mm Hg. Transcutaneous Po2 increased over time in both groups, with significant differences favoring the liraglutide group after 6 months (estimated treatment difference, 11.2 mm Hg; 95% CI, 8.0-14.5 mm Hg; P < .001). The 10% increase of TcPo2 occurred in 24 participants (89%) in the liraglutide group and 13 (46%) in the control group (relative risk, 1.91; 95% CI, 1.26-2.90; P < .001). Compared with the control group, individuals in the liraglutide group had a significant reduction of C-reactive protein (-0.4 mg/dL; 95% CI, -0.7 to -0.07 mg/dL; P = .02), urinary albumin to creatinine ratio (-119.4 mg/g; 95% CI, -195.0 to -43.8 mg/g; P = .003), and improvement of 6-minute walking distance (25.1 m; 95% CI, 21.8-28.3 m; P < .001). Conclusions and Relevance: In this randomized clinical trial of people with type 2 diabetes and PAD, liraglutide increased peripheral perfusion detected by TcPo2 measurement during 6 months of treatment. These results support the use of liraglutide to prevent the clinical progression of PAD in individuals with type 2 diabetes. Trial Registration: ClinicalTrials.gov Identifier: NCT04881110.

Hepatic and adipose tissue transcriptome analysis highlights a commonly deregulated autophagic pathway in severe MASLD.

OBJECTIVE: The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly ramping up due to the spread of obesity, which is characterized by expanded and dysfunctional visceral adipose tissue (VAT). Previous studies have investigated the hepatic transcriptome across MASLD, whereas few studies have focused on VAT. METHODS: We performed RNA sequencing in 167 hepatic samples from patients with obesity and in a subset of 79 matched VAT samples. Circulating cathepsin D (CTSD), a lysosomal protease, was measured by ELISA, whereas the autophagy-lysosomal pathway was assessed by Western blot in hepatic and VAT samples (n = 20). RESULTS: Inflammation, extracellular matrix remodeling, and mitochondrial dysfunction were upregulated in severe MASLD in both tissues, whereas autophagy and oxidative phosphorylation were reduced. Tissue comparative analysis revealed 13 deregulated genes, including CTSD, which showed the most robust diagnostic accuracy in discriminating mild and severe MASLD. CTSD expression correlated with circulating protein, whose increase was further validated in 432 histologically characterized MASLD patients, showing a high accuracy in foreseeing severe liver injury. In addition, the assessment of serum CTSD increased the performance of fibrosis 4 in diagnosing advanced disease. CONCLUSIONS: By comparing the hepatic and VAT transcriptome during MASLD, we refined the concept by which CTSD may represent a potential biomarker of severe disease.

A narrative review about cognitive impairment in metabolic Dysfunction-Associated liver disease (MASLD): Another matter to face through a holistic approach.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic hepatic disorder worldwide in both adults and children. It is well established that MASLD represents the hepatic manifestation of the metabolic syndrome whose definition includes the presence of obesity, type 2 diabetes (T2D), dyslipidemia, hypertension and hypercoagulability. All these conditions contribute to a chronic inflammatory status which may impact on blood brain barrier (BBB) integrity leading to an impaired function of central nervous system (CNS). AIM OF REVIEW: Since the mechanisms underlying the brain-liver-gut axis derangement are still inconclusive, the present narrative review aims to make a roundup of the most recent studies regarding the cognitive decline in MASLD also highlighting possible therapeutic strategies to reach a holistic advantage for the patients. KEY SCIENTIFIC CONCEPTS OF REVIEW: Due to its ever-growing prevalence, the MASLD-related mental dysfunction represents an enormous socio-economic burden since it largely impacts on the quality of life of patients as well as on their working productivity. Indeed, cognitive decline in MASLD translates in low concentration and processing speed, reduced memory, sleepiness but also anxiety and depression. Chronic systemic inflammation, hyperammonemia, genetic background and intestinal dysbiosis possibly contribute to the cognitive decline in MASLD patients. However, its diagnosis is still underestimated since the leading mechanisms are multi-faceted and unexplained and do not exist standardized diagnostic tools or cognitive test strategies. In this scenario, nutritional and lifestyle interventions as well as intestinal microbiota manipulation (probiotics, fecal transplantation) may represent new approaches to counteract mental impairment in these subjects. In sum, to face the "mental aspect" of this multifactorial disease which is almost unexplored, cognitive tools should be introduced in the management of MASLD patients.

Two years with GIOIA 'Effects of gliflozins and gliptins on markers of cardiovascular damage in type 2 diabetes': A prospective, multicentre, quasi-experimental study on sodium-glucose cotransporter 2 and dipeptidyl peptidase-4 inhibitors in diabetes clinical practice.

AIM: To assess and compare the metabolic and vascular effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) in the clinical practice of patients with type 2 diabetes in Italy. MATERIALS AND METHODS: GIOIA is a 2-year prospective, multicentre, quasi-experimental study that enrolled patients with type 2 diabetes initiating SGLT-2i or DPP-4i for inadequate glycaemic control [glycated haemoglobin (HbA1c) >7%] between March 2018 and March 2021. The primary endpoints were changes in markers of organ damage [carotid intima-media thickness (CIMT), albuminuria, myocardial function] and HbA1c from baseline to year 2. RESULTS: In total, 1150 patients were enrolled in the study (SGLT-2i n = 580, DPP-4i n = 570). Patients initiated on SGLT-2i were younger (about 6 years) and heavier (about 11 kg), had higher HbA1c level (1% more), more albuminuria and cardiovascular events (16% more) than patients initiated on DPP-4i. CIMT and echocardiographic parameters were not significantly different. Propensity score matching yielded two groups, each consisting of 155 patients with diabetes with similar baseline characteristics. Despite a significant similar reduction in HbA1c levels in both groups (-0.8%), more patients on SGLT-2i had regression of CIMT and albuminuria (22% and 10%, respectively, p < .001 vs. DPP-4i); more patients on DPP-4i had progression of CIMT and albuminuria (23% and 28%, respectively, p < .001 vs. SGLT-2i). Left ventricular ejection fraction improved slightly (3%, p = .043) on SGLT-2i only. CONCLUSIONS: In a real-world setting, both SGLT-2i and DPP-4i improve glycaemic control persisting after 2 years of treatment, with a robust effect on both CIMT and albuminuria regression for SGLT-2i as compared with DPP-4i in the propensity score matching.

Telemedicine for type 2 diabetes during COVID-19 pandemic: experience from a tertiary diabetes center.

BACKGROUND: Telemedicine was largely employed during COVID-19 pandemic to guarantee continuity of care in a period of dramatic reduction of face-to-face visits. The aim of this study was to describe the clinical characteristics of a cohort of patients with type 2 diabetes followed by tele-visits and to evaluate the changes in the glyco-metabolic control during a 12-month follow-up. METHODS: This retrospective observational study included 136 adults aged >18 years with at least three tele-visits over a 12-month follow-up period, in a Diabetes Center of the Southern Italy, from April 2020 to March 2022. Data related to glycemic and lipid profile, therapy, presence of micro or macrovascular complications, and other clinical features were extracted at three time points, at first visit (T0), after 6 months (T1) and after 12 months (T2). RESULTS: Mean diabetes duration and median HbA1c values were 11.6 years and 7.0%, respectively. Thirty-eight participants (27.9%) presented macro- or microvascular complications. Glycemic control remained stable over time, without clinically significant changes of HbA1c (T0 vs. T1 vs. T2, median [IQR], 7.0 [6.2-7.3], 6.6 [6.0-7.5], 6.9 [6.2-7.5], P=0.095) and fasting glucose. Lipid profile slightly improved, although without significant clinical change. Glucose lowering therapy was modified in 84 patients (61.8%) and remained unchanged in 52 patients (38.2%) during the follow-up. No participant in the study developed any complications during the 12-month follow-up. CONCLUSIONS: People with type 2 diabetes followed by telemedicine were adults with fair glucose control generally free from chronic complications, whose diabetes control did not worsen during a 12-month follow-up.