Clinical Effectiveness and Safety of Once-Weekly GLP-1 Receptor Agonist Dulaglutide as Add-On to Metformin or Metformin Plus Insulin Secretagogues in Obesity and Type 2 Diabetes

Aims and methods: The aim of this monocentric retrospective observational study was to evaluate the 18-month safety and effectiveness of GLP-1 receptor agonist (GLP-1 RA) dulaglutide (DU) 1.5 mg/once weekly as an add-on to metformin (MET) or MET plus conventional insulin secretagogues in a study cohort with excess body weight and type 2 diabetes (T2D). Comparative efficacy versus liraglutide (LIRA) 1.2–1.8 mg/once daily in a study sample naïve to GLP-1 RAs, frequency matching for age, gender, T2D duration, degree of glycemic impairment, cardiovascular comorbidities, and medications, was addressed as a secondary aim. Clinical and biochemical data for efficacy outcomes and information on drug discontinuation due to adverse events (AEs) were collected from digital records. Results: Initial analysis included 126 overweight and obese T2D patients (48.4% females). Out of these, 13 discontinued DU due to moderate–severe gastrointestinal AEs after a mean follow-up of 6 (4 standard deviations (SD)) months, while 65 completed 18 months of continuous therapy. At 6 months, there was a significant mean HbA1c reduction of −0.85% (1.17 SD) with respect to baseline values (p < 0.001), which remained stable during 18 months follow-up. These results were accompanied by a moderate weight loss sustained over time, with a mean reduction of −2.0% (4.3 SD) at 6 months and −1.3% (4.8 SD) at 18 months (p = 0.091). At univariate analysis, a negative correlation between baseline body mass index (BMI) and risk of drug discontinuation due to gastrointestinal AEs was observed. The protective effect of obesity against drug discontinuation was confirmed by logistic regression analysis. Neither gender, nor age, nor T2D duration, nor concomitant conventional insulin secretagogue use, nor switching to DU from other GLP-1 RAs influenced its long-term effectiveness. However, higher baseline HbA1c values emerged as predictors of clinically relevant efficacy outcomes, either in terms of HbA1c reduction ≥ 0.5% or body weight loss ≥ 5%. The efficacy outcomes were corroborated by head-to-head comparison with LIRA, a GLP-1 RA with durable beneficial effects on glycemic control and body weight in real-world experiences. With the advantage of once-weekly administration, at 18-month follow-up, a significantly larger fraction of patients on DU therapy reached glycemic targets (HbA1c ≤ 7.0%) when compared to those on LIRA: from 14.8% at baseline (both groups) to 64.8% with DU and 42.6% with LIRA (p = 0.033). Conclusions: Although limited by a retrospective design and lack of constant up-titration for LIRA to the highest dose, these findings indicate that the beneficial responses to DU on a background of MET or MET plus insulin secretagogues are durable, especially in the presence of obesity and greater HbA1c impairment

Adrenal incidentaloma: a case of carcinoma

Adrenal incidentaloma (AI) is a term applied to an accidentally discovered adrenal mass on imaging performed for reasons unrelated to adrenal pathology. The widespread application of abdominal imaging procedure has resulted in an increased frequency of clinically silent adrenal masses. Although most AIs are nonfunctioning benign adenomas, a multidisciplinary approach with biochemical and radiological evaluation is needed to characterize these lesions and identify patients who are at high risk for hormonal or malignant evolution. Herein, we describe a case of a 69-year-old man with a pain at the base of right chest. On the basis of clinical evaluation, biochemical analysis, as well as imaging procedures, a diagnosis of right adrenocortical carcinoma was made. The patient underwent medical treatment

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P &lt; 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P &lt; 0.001), sNox2-dp (r(s), -0.57; P &lt; 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P &lt; 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p &lt; .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p &lt; .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Adrenal incidentaloma: a case of carcinoma

Giovanni Ruotolo1, Maria Raffaella Ambrosio5, Patrizia Rosa Caroleo1, Elvira Bonacci1, Anna Maria Condito2, Alfonso Merante1, Pierpaolo Arcuri3, Bruno Jim Rocca5, Bianca Virginia Palermo4, Saverio Palermo4, Pietro Gareri61Head Physician Geriatric Unit, 2Emergency Medicine Unit, 3Division of Radiology, 4Nuclear Medicine Unit, &ldquo;Pugliese-Ciaccio&rdquo; Hospital, Catanzaro, Italy; 5Department of Human Pathology and Oncology, Pathological Anatomy Section, University of Siena, Siena, Italy; 6Elderly Health Care, ASP Catanzaro, Catanzaro, ItalyAbstract: Adrenal incidentaloma (AI) is a term applied to an accidentally discovered adrenal mass on imaging performed for reasons unrelated to adrenal pathology. The widespread application of abdominal imaging procedure has resulted in an increased frequency of clinically silent adrenal masses. Although most AIs are nonfunctioning benign adenomas, a multidisciplinary approach with biochemical and radiological evaluation is needed to characterize these lesions and identify patients who are at high risk for hormonal or malignant evolution. Herein, we describe a case of a 69-year-old man with a pain at the base of right chest. On the basis of clinical evaluation, biochemical analysis, as well as imaging procedures, a diagnosis of right adrenocortical carcinoma was made. The patient underwent medical treatment.Keywords: adrenal incidentaloma, adrenal mass, adrenocortical carcinom

Appropriate Timing of Gestational Diabetes Mellitus Diagnosis in Medium- and Low-Risk Women: Effectiveness of the Italian NHS Recommendations in Preventing Fetal Macrosomia

Background. Screening strategies for gestational diabetes mellitus (GDM) earlier than 24-28 weeks of gestation should be considered to prevent adverse pregnancy outcomes. Nonetheless, there is uncertainty about which women would benefit most from early screening and which screening strategies should be offered to women with GDM. The Italian National Healthcare Service (NHS) recommendations on selective screening for GDM at 16-18 weeks of gestation are effective in preventing fetal macrosomia in high-risk (HR) women, but the appropriateness of timing and effectiveness of these recommendations in medium- (MR) and low-risk (LR) women are still controversial. Patients and Methods. We retrospectively enrolled 769 consecutive singleton pregnant women who underwent both anomaly scan at 19-21 weeks of gestation and screening for GDM at 16-18 and/or 24-28 weeks of gestation, in agreement with the NHS recommendations and risk stratification criteria. Comparison of maternal characteristics, fetal biometric parameters at anomaly scan (head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC), femur length (FL), estimated fetal weight (EFW)), and neonatal birth weight (BW) percentile among risk groups was examined. Results. 219 (28.5%) women were diagnosed with GDM, while 550 (71.5%) were normal glucose-tolerant women. Out of 164 HR women, only 62 (37.8%) underwent the recommended early screening for GDM at 16-18 weeks of gestation. AC and EFW percentiles, as well as neonates’ BW percentiles, were significantly higher in HR women diagnosed with GDM at 24-28 weeks of gestation with respect to normal glucose-tolerant women, as well as MR and LR women who tested positive for GDM. Comparative analysis between MR and LR women with GDM and women with normal glucose tolerance revealed significant differences in both AC and EFW percentiles (P<0.05), while there was no significant difference in neonatal BW percentiles. Conclusion. In MR and LR women with GDM, a mild acceleration of fetal growth can be detected at the time of anomaly scan. However, in these at-risk categories, the NHS recommendations for screening and treatment of GDM at 24-28 weeks of gestation are still effective in normalizing BW and preventing fetal macrosomia, thus supporting a risk factor-based selective screening program for GDM

First Trimester Combined Test (FTCT) as a Predictor of Gestational Diabetes Mellitus

Background&mdash;The first trimester combined test (FTCT) is an effective screening tool to estimate the risk of fetal aneuploidy. It is obtained by the combination of maternal age, ultrasound fetal nuchal translucency (NT) measurement, and the maternal serum markers free &beta;-human chorionic gonadotropin (&beta;-hCG) and pregnancy-associated plasma protein A (PAPP-A). However, conflicting data have been reported about the association of FTCT, &beta;-hCG, or PAPP-A with the subsequent diagnosis of gestational diabetes mellitus (GDM). Research design and methods&mdash;2410 consecutive singleton pregnant women were retrospectively enrolled in Calabria, Southern Italy. All participants underwent examinations for FTCT at 11&ndash;13 weeks (plus 6 days) of gestation, and screening for GDM at 16&ndash;18 and/or 24&ndash;28 weeks of gestation, in accordance with current Italian guidelines and the International Association Diabetes Pregnancy Study Groups (IADPSG) glycemic cut-offs. Data were examined by univariate and logistic regression analyses. Results&mdash;1814 (75.3%) pregnant women were normal glucose tolerant, while 596 (24.7%) were diagnosed with GDM. Spearman univariate analysis demonstrated a correlation between FTCT values and subsequent GDM diagnosis (&rho; = 0.048, p = 0.018). The logistic regression analysis showed that women with a FTCT &lt;1:10000 had a major GDM risk (p = 0.016), similar to women with a PAPP-A &lt;1 multiple of the expected normal median (MoM, p = 0.014). Conversely, women with &beta;-hCG &ge;2.0 MoM had a reduced risk of GDM (p = 0.014). Conclusions&mdash;Our findings indicate that GDM susceptibility increases with fetal aneuploidy risk, and that FTCT and its related maternal serum parameters can be used as early predictors of GDM

Brain-Behavior-Immune Interaction: Serum Cytokines and Growth Factors in Patients with Eating Disorders at Extremes of the Body Mass Index (BMI) Spectrum

Alterations of the immune system are known in eating disorders (EDs), however the importance of cytokine balance in this context has not been clarified. We compared cytokines and growth factors at opposite ends of BMI ranges, in 90 patients classified in relation to BMI, depressive and EDs comorbidities. Serum concentrations of interleukin (IL)-1&alpha;, IL-1&beta;, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (IFN-&gamma;), tumor necrosis factor-alpha (TNF-&alpha;), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were determined by a biochip analyzer (Randox Labs). Differences were calculated through ANOVA. Possible predictors of higher cytokine levels were evaluated through regression analysis. IL-1&alpha;, IL-10, EGF, and IFN-&gamma; were altered individuals with anorexia nervosa (AN) and binge eating disorder (BED). Night-eating was associated with IL-8 and EGF levels, IL-10 concentrations with post-dinner eating and negatively with sweet-eating, long fasting with higher IFN-&gamma; levels. IL-2 increase was not linked to EDs, but to the interaction of depression and BMI. Altogether, for the first time, IL-1&alpha;, IL-10, EGF, and IFN-&gamma; were shown to differ between AN and HCs, and between AN and individuals with obesity with or without BED. Only IL-2 was influenced by depression. Dysfunctional eating behaviors predicted abnormal concentrations of IL-10, EGF, IL-8 and IFN-&gamma;