Liraglutide Improves Cardiovascular Risk as an Add-on to Metformin and Not to Insulin Secretagogues in Type 2 Diabetic Patients: A Real-life 48-Month Retrospective Study.

INTRODUCTION: Although liraglutide is widely recognized to have glycemic and extra-glycemic effects, few studies have compared these effects in relation to hypoglycemic treatment starting from the diagnosis of diabetes. We evaluated the effectiveness of liraglutide in reducing the Framingham risk score (FRS) and visceral adiposity index (VAI) in relation to first-line hypoglycemic treatment from diagnosis of type 2 diabetes, continued without any changes. METHODS: We selected 105 diabetic outpatients who were treated with liraglutide for at least 48 months as an add-on therapy to metformin alone (group A, n = 52) or insulin secretagogues (group B, n = 53) from diagnosis time. RESULTS: Although both groups showed a reduction in BMI, waist circumference, blood pressure, HbA1c and triglycerides, only group A showed a significant reduction in FRS (p < 0.001) and VAI (p = 0.012) after 48 months. No significant intergroup difference was found for any parameters at either baseline or 48 months, with the exception of FRS at 48 months, lower in group A (p = 0.002), regardless of duration of disease, improvement in glycemic control and VAI. CONCLUSION: Our data show that during a 48-month follow-up liraglutide was more efficacious in reducing cardiovascular risk than when it was used as add-on therapy to the first-line therapy from diagnosis with metformin and not with insulin secretagogues

One Year of Dapaglifozin Add-On Therapy Ameliorates Surrogate Indexes of Insulin Resistance and Adiposity in Patients with Type 2 Diabetes Mellitus

Introduction: This study investigates the effects of dapagliflozin on the visceral adiposity index (VAI), lipid accumulation product (LAP), product of triglycerides and glucose (TyG) and triglycerides to HDL-cholesterol ratio (TG/HDL-C) in patients with type 2 diabetes mellitus (T2D). Methods: In this real-life study, dapaglifozin was added to metformin alone (group 1, no. 42) or insulin plus metformin (group 2, no. 58) in 100 T2D patients. Results: In group 1, after 6 months of dapaglifozin addition, a significant decrease in BMI (p < 0.001), waist circumference (WC) (p < 0.001), systolic blood pressure (SBP) (p = 0.009), diastolic blood pressure (DBP) (p = 0.012), mean fasting blood glucose (FBG), post-breakfast glucose (PBG), post-lunch glucose (PLG) and post-dinner glucose (PDG) (all p < 0.001), HbA1c (p < 0.001), VAI (p = 0.020), LAP (p = 0.028), Tyg (p < 0.001), TG/HDL-C (p = 0.020) and glutamate pyruvate transaminase (GPT) (p < 0.001) was observed compared to baseline. After 12 months a significant decrease in BMI (p < 0.001), WC (p = 0.006), SBP (p = 0.023), DBP (p = 0.005), mean FPG, PBG, PLG and PDG (all p < 0.001), HbA1c (p < 0.001), total cholesterol (p = 0.038), triglycerides (p = 0.026), VAI (p = 0.013), GPT (p < 0.001), LAP index (p = 0.024), Tyg index (p < 0.001) and TG/HDL-c ratio (p = 0.016) was observed compared to baseline. In group 2, after 6 months of dapaglifozin addition, a significant decrease in BMI (p < 0.001), WC (p < 0.001), SBP (p = 0.015), DBP (p = 0.007), mean FPG, PBG, PLG and PDG (all p < 0.001), HbA1c (p < 0.001), VAI (p = 0.040), LAP (p = 0.047), Tyg (p < 0.001), TG/HDL-C (p = 0.048) and GPT (p < 0.001) was observed compared to baseline. By contrast, after 12 months a significant decrease in BMI (p < 0.001), WC (p < 0.001), SBP (p = 0.001), DBP (p = 0.002), mean FPG, PBG, PLG and PDG (all p < 0.001), HbA1c (p < 0.001), GPT (p < 0.001) and Tyg index (p = 0.003) was observed compared to baseline. Conclusions: Dapagliflozin treatment significantly reduced surrogate indexes of insulin resistance and adiposity in patients with T2D

Correlation between adrenal function, growth hormone secretion, and insulin sensitivity in children with idiopathic growth hormone deficiency

Purpose Patients with growth hormone deficiency (GHD) demonstrate an increased cortisol/cortisone ratio which could potentially explain the metabolic features of GHD, while GH treatment (GHT) could increase the cortisol metabolism. Methods In 35 children (27 M, mean age 10.1 years) with idiopathic GHD at baseline and after 12 months of GHT and in 25 controls, in addition to metabolic parameters, we assessed adrenal function by morning serum cortisol, its peak, and its area under the curve (AUCCOR) during insulin tolerance test (ITT). Results A cortisol peak <18 \ub5g/dl was shown in 22 and 31% of GHD children at baseline and after GHT, respectively. At baseline, GHD children had lower fasting glucose (p < 0.001) and ISI-Matsuda (p = 0.042), with concomitant higher Homa-IR (p = 0.006) and morning cortisol (p = 0.012) than controls. Morning cortisol was negatively correlated with GH (p < 0.001), fasting glucose (p < 0.001) and ISI-Matsuda (p < 0.001) and positively with Homa-IR (p = 0.010). Both cortisol peak and AUCCOR were negatively correlated with GH (all p < 0.001) and ISI-Matsuda (p = 0.016 and p = 0.001, respectively). After 12 months of GHT, a significant increase in fasting glucose (p < 0.001), and Homa-IR (p = 0.011) was documented, with a concomitant decrease in morning cortisol (p = 0.002), AUCCOR (p = 0.038), total (p = 0.003) and LDL-cholesterol (p = 0.016). No significant correlations were found among cortisol levels and all parameters were investigated. Conclusions Cortisol levels correlate with GH secretion and with many metabolic parameters in GHD children, while the metabolic effects during GHT are mainly due to GHT per se and less to cortisol reduction

BCR-ABL1 doubling-times and halving-times may predict CML response to tyrosine kinase inhibitors

In Chronic Myeloid Leukemia (CML), successful treatment requires accurate molecular monitoring to evaluate disease response and provide timely interventions for patients failing to achieve the desired outcomes. We wanted to determine whether measuring BCR-ABL1 mRNA doubling-times (DTs) could distinguish inconsequential rises in the oncogene’s expression from resistance to tyrosine kinase inhibitors (TKIs). Thus, we retrospectively examined BCR-ABL1 evolution in 305 chronic-phase CML patients receiving imatinib mesylate (IM) as a first line treatment. Patients were subdivided in two groups: those with a confirmed rise in BCR-ABL1 transcripts without MR3.0 loss and those failing IM. We found that the DTs of the former patients were significantly longer than those of patients developing IM resistance (57.80 vs. 41.45 days, p = 0.0114). Interestingly, the DT values of individuals failing second-generation (2G) TKIs after developing IM resistance were considerably shorter than those observed at the time of IM failure (27.20 vs. 41.45 days; p = 0.0035). We next wanted to establish if decreases in BCR-ABL1 transcripts would identify subjects likely to obtain deep molecular responses. We therefore analyzed the BCR-ABL1 halving-times (HTs) of a different cohort comprising 174 individuals receiving IM in first line and observed that, regardless of the time point selected for our analyses (6, 12, or 18 months), HTs were significantly shorter in subjects achieving superior molecular responses (p = 0.002 at 6 months; p &lt; 0.001 at 12 months; p = 0.0099 at 18 months). Moreover, 50 patients receiving 2G TKIs as first line therapy and obtaining an MR3.0 (after 6 months; p = 0.003) or an MR4.0 (after 12 months; p = 0.019) displayed significantly shorter HTs than individuals lacking these molecular responses. Our findings suggest that BCR-ABL1 DTs and HTs are reliable tools to, respectively, identify subjects in MR3.0 that are failing their assigned TKI or to recognize patients likely to achieve deep molecular responses that should be considered for treatment discontinuation

TWO CASES OF NON-ALCOHOLIC WERNICKE ENCEPHALOPATHY SUCCESSFULLY TREATED BY THIAMINE REPLACEMENT: DIAGNOSTIC AND THERAPEUTIC CONSIDERATIONS

Wernicke\u2019s encephalopathy (WE) is an acute neurologi- cal disorder, due to a lack of thiamin (vitamin B1) which is observed mainly in alcoholic patients. Unfortunately, the syn- drome is underestimated in clinical practice and most often recognized only on autopsy, especially among non-alcoholics. The common clinical picture include mental status changes, ocular dysfunction, and gait ataxia. Treatment consists of timely thiamine replacement through intravenous infusion. We describe the case of two patients who developed a non-alcoholic WE post-surgical, regressed completely after intravenous infusion of thiamine. These cases suggest intere- sting diagnostic and therapeutic implications

Clinical implications of discordant early molecular responses in CML patients treated with imatinib

A reduction in BCR-ABL1/ABL1IS transcript levels to &lt;10% after 3 months or &lt;1% after 6 months of tyrosine kinase inhibitor therapy are associated with superior clinical outcomes in chronic myeloid leukemia (CML) patients. In this study, we investigated the reliability of multiple BCR-ABL1 thresholds in predicting treatment outcomes for 184 subjects diagnosed with CML and treated with standard-dose imatinib mesylate (IM). With a median follow-up of 61 months, patients with concordant BCR-ABL1/ABL1IS transcripts below the defined thresholds (10% at 3 months and 1% at 6 months) displayed significantly superior rates of event-free survival (86.1% vs. 26.6%) and deep molecular response (≥ MR4; 71.5% vs. 16.1%) compared to individuals with BCR-ABL1/ABL1IS levels above these defined thresholds. We then analyzed the outcomes of subjects displaying discordant molecular transcripts at 3-and 6-month time points. Among these patients, those with BCR-ABL1/ABL1IS values &gt;10% at 3 months but &lt;1% at 6 months fared significantly better than individuals with BCR-ABL1/ABL1IS &lt;10% at 3 months but &gt;1% at 6 months (event-free survival 68.2% vs. 32.7%; p &lt; 0.001). Likewise, subjects with BCR-ABL1/ABL1IS at 3 months &gt;10% but &lt;1% at 6 months showed a higher cumulative incidence of MR4 compared to patients with BCR-ABL1/ABL1IS &lt;10% at 3 months but &gt;1% at 6 months (75% vs. 18.2%; p &lt; 0.001). Finally, lower BCR-ABL1/GUSIS transcripts at diagnosis were associated with BCR-ABL1/ABL1IS values &lt;1% at 6 months (p &lt; 0.001). Our data suggest that when assessing early molecular responses to therapy, the 6-month BCR-ABL1/ABL1IS level displays a superior prognostic value compared to the 3-month measurement in patients with discordant oncogenic transcripts at these two pivotal time points

Practical Approach to the Diagnosis of the Vulvo-Vaginal Stromal Tumors: An Overview

Background: The category of the "stromal tumors of the lower female genital tract" encompasses a wide spectrum of lesions with variable heterogeneity, which can be nosologically classified on the basis of their morphologic and immunohistochemical profiles as deep (aggressive) angiomyxoma (DAM), cellular angiofibroma (CAF), angiomyofibroblastoma (AMFB) or myofibroblastoma (MFB). Despite the differential diagnosis between these entities being usually straightforward, their increasingly recognized unusual morphological variants, along with the overlapping morphological and immunohistochemical features among these tumours, may raise serious differential diagnostic problems. Methods and Results: The data presented in the present paper have been retrieved from the entire published literature on the PubMed website about DAM, CAF, AFMB and MFB from 1984 to 2021. The selected articles are mainly represented by small-series, and, more rarely, single-case reports with unusual clinicopathologic features. The present review focuses on the diagnostic clues of the stromal tumours of the lower female genital tract to achieve a correct classification. The main clinicopathologic features of each single entity, emphasizing their differential diagnostic clues, are discussed and summarized in tables. Representative illustrations, including the unusual morphological variants, of each single tumour are also provided. Conclusion: Awareness by pathologists of the wide morphological and immunohistochemical spectrum exhibited by these tumours is crucial to achieve correct diagnoses and to avoid confusion with reactive conditions or other benign or malignant entities

Diabetic foot ulcers: Retrospective comparative analysis from Sicily between two eras

Aim: The aim of this study was to analyze changes in the incidence, management and mortality of DFU in Sicilian Type 2 diabetic patients hospitalized between two eras, i.e. 2008-2013 and 2014-2019. Methods: We compared the two eras, era1: 2008-13, era2: 2014-19. In era 1, n = 149, and in era 2, n = 181 patients were retrospectively enrolled. Results: In the population hospitalized for DFU in 2008-2013, 59.1% of males and 40.9% of females died, whilst in 2014-2019 65.9% of males and 34.1% of females died. Moderate chronic kidney disease (CKD) was significantly higher in patients that had died than in ones that were alive (33% vs. 43%, p &lt; 0.001), just as CKD was severe (14.5% vs. 4%, p &lt; 0.001). Considering all together the risk factors associated with mortality, at Cox regression multivariate analysis only moderate-severe CKD (OR 1.61, 95% CI 1.07-2.42, p 0.021), age of onset greater than 69 years (OR 2.01, 95% CI 1.37-2.95, p &lt;0.001) and eGFR less than 92 ml/min (OR 2.84, 95% CI 1.51-5.34, p 0.001) were independently associated with risk of death. Conclusions: Patients with DFU have high mortality and reduced life expectancy. Age at onset of diabetic foot ulcer, eGFR values and CKD are the principal risk factors for mortality