Urinary Post-Translationally Modified Fetuin-A (uPTM-FetA) in Chronic Kidney Disease Patients with and without Diabetic Kidney Disease.

Background and Objectives: A novel post-translational modification (PTM) fragment derived from the cleavage of Fetuin-A (PTM-FetA) has recently emerged as a sensitive biomarker for kidney damage in diabetic patients, but evidence in other chronic renal diseases is lacking. In this pilot study, we aimed at evaluating the clinical significance of urinary PTM-FetA (uPTM-FetA) in a mixed cohort of patients with non-advanced chronic kidney disease (CKD) secondary to diabetic kidney disease (DKD) or other causes. Materials and Methods: We enrolled 47 adult patients with CKD (mean CKD-Epi 40.10 ± 16.5 mL/min/1.73 m2) due to DKD (n = 34) or other etiology (n = 13). uPTM-FetA was measured in the urine using a commercially available ELISA kit. Fifteen healthy individuals served as controls. Results: Collectively, all CKD patients displayed remarkably higher levels of uPTM-FetA than controls (0.84 [0.10-1.15] vs. 29.68 [2.50-55.16] ng/mL p = 0.0005), but values were lower in non-DKD than in DKD patients (1.66 [0.09-4.19] vs. 13.9 [0.01-45.02] ng/mL; p = 0.01). uPTM-FetA showed a great diagnostic capacity at ROC analyses to identify the presence of CKD (AUC 0.776; p < 0.001) and, within CKD patients, to discriminate the diabetic and non-diabetic etiology (AUC 0.673; p = 0.02). At multivariate correlation analyses, proteinuria (ß = 0.442; p = 0.02) and BMI (ß = -0.334; p = 0.04) were the sole independent predictors of uPTM-FetA in this study population. Conclusions: uPTM-FetA could be a novel sensitive biomarker at the crossroad of chronic renal damage and metabolic dysfunction. Additionally, this biomarker could also represent a non-invasive, complementary tool for discriminating among different CKD etiologies (DKD vs. non-DKD) in difficult cases or when renal biopsy is not available.

miRNAs in Uremic Cardiomyopathy: A Comprehensive Review.

Uremic Cardiomyopathy (UCM) is an irreversible cardiovascular complication that is highly pervasive among chronic kidney disease (CKD) patients, particularly in End-Stage Kidney Disease (ESKD) individuals undergoing chronic dialysis. Features of UCM are an abnormal myocardial fibrosis, an asymmetric ventricular hypertrophy with subsequent diastolic dysfunction and a complex and multifactorial pathogenesis where underlying biological mechanisms remain partly undefined. In this paper, we reviewed the key evidence available on the biological and clinical significance of micro-RNAs (miRNAs) in UCM. miRNAs are short, noncoding RNA molecules with regulatory functions that play a pivotal role in myriad basic cellular processes, such as cell growth and differentiation. Deranged miRNAs expression has already been observed in various diseases, and their capacity to modulate cardiac remodeling and fibrosis under either physiological or pathological conditions is well acknowledged. In the context of UCM, robust experimental evidence confirms a close involvement of some miRNAs in the key pathways that are known to trigger or worsen ventricular hypertrophy or fibrosis. Moreover, very preliminary findings may set the stage for therapeutic interventions targeting specific miRNAs for ameliorating heart damage. Finally, scant but promising clinical evidence may suggest a potential future application of circulating miRNAs as diagnostic or prognostic biomarkers for improving risk stratification in UCM as well.

In Vitro Evaluation of Ferutinin Rich-Ferula communis L., ssp. glauca, Root Extract on Doxorubicin-Induced Cardiotoxicity: Antioxidant Properties and Cell Cycle Modulation.

The clinical use of anthracycline Doxorubicin as an antineoplastic drug in cancer therapy is limited by cardiotoxic effects that can lead to congestive heart failure. Recent studies have shown several promising activities of different species of the genus Ferula belonging to the Apiaceae Family. Ferula communis is the main source of Ferutinin-a bioactive compound isolated from many species of Ferula-studied both in vitro and in vivo because of their different effects, such as estrogenic, antioxidant, anti-inflammatory, and also antiproliferative and cytotoxic activity, performed in a dose-dependent and cell-dependent way. However, the potential protective role of Ferutinin in myocardium impairment, caused by chemotherapeutic drugs, still represents an unexplored field. The aim of this study was to test the effects of Ferutinin rich-Ferula communis L. root extract (FcFE) at different concentrations on H9C2 cells. Moreover, we evaluated its antioxidant properties in cardiomyocytes in order to explore new potential therapeutic activities never examined before in other experimental works. FcFE, at a concentration of 0.25 µM, in the H9C2 line, significantly reduced the ROS production induced by H2O2 (50 µM and 250 µM) and traced the cell mortality of the H9C2 co-treated with Ferutinin 0.25 µM and Doxorubicin (0.5 µM and 1 µM) to control levels. These results showed that FcFE could protect against Doxorubicin-induced cardiotoxicity. Further molecular characterization of this natural compound may open the way for testing FcFE at low concentrations in vivo and in clinical studies as an adjuvant in cancer therapy in association with anthracyclines to prevent side effects on heart cells.

Urinary Marinobufagenin in Patients with Non-Advanced Chronic Kidney Disease: A Cross-Sectional Study.

Background and Objectives: The global prevalence of chronic kidney disease (CKD) is on the rise, posing important challenges for healthcare systems. Thus, the search for new factors potentially involved in the pathogenesis, progression and complications of early CKD remains urgent. Marinobufagenin (MBG) is a natriuretic endogenous cardiotonic steroid, and increased circulating levels of it may accelerate kidney damage. In this study, we explored the possible clinical significance of measuring urinary marinobufagenin (uMBG) in patients with non-advanced CKD. Materials and Methods: One hundred and eight adult CKD patients (mean age 71.6 ± 10 years, 70.4% male; mean eGFR 40.54 ± 17 mL/min/1.73 m2) were enrolled in this cross-sectional study. uMBG was measured together with a series of clinical, anthropometric, laboratory and instrumental analyses. Twenty-five healthy matched subjects served as controls for the uMBG measurement. Results: The uMBG values were lower in the patients with CKD as compared to those of the controls (0.37 [IQR: 0.25-0.45] vs. 0.64 [0.46-0.78] nmol/L. p = 0.004), and a significant trend in eGFR levels was noticed across the decreasing uMBG tertiles (p = 0.03). Regarding the correlation analyses, the uMBG values remained robustly associated with the eGFR in multivariate models employing either uMBG or eGFR as the dependent variable (ß = 0.248; p = 0.01 and ß = 0.139; p = 0.04, respectively). Besides the eGFR, the independent predictors of uMBG values in this population were the use of statins (ß = -0.326; p = 0.001), the presence of diabetes (ß = 0.243; p = 0.009) and urine sodium (ß = 0.204; p = 0.01). Conclusions: Reduced uMBG excretion may reflect impaired renal clearance, which may contribute to the detrimental effects attributed to this hormone due to systemic accumulation. Future studies are needed to clarify the biological mechanisms placing uMBG at the crossroad of sodium intake and the presence of diabetes in CKD-suffering individuals and to verify whether a statin treatment may somewhat limit the detrimental effects of MBG in the presence of impaired renal function.

Decreased Cathepsin-K Mirrors the Severity of Subclinical Atherosclerosis in Kidney Transplant Recipients.

Background: In kidney transplantation (Ktx) recipients, cardiovascular (CV) disease remains the leading cause of death. Abnormal carotid intima-media thickness (IMT) represents a valid indicator of incipient atherosclerosis also in this setting. Cathepsin-K (CatK) is a cysteine protease involved in vascular remodelling, as well as in progressive atherosclerosis. In this study we evaluated clinical predictors of CatK in Ktx recipients, with a particular focus on its possible relationships with subclinical atherosclerosis. Methods: Circulating CatK was measured in 40 stable Ktx recipients together with several laboratory, clinical and echocardiography parameters. 30 healthy subjects and 30 hemodialysis (HD) patients served as controls for CatK values. Carotid IMT was measured in Ktx and these subjects were then categorized according to age-gender reference cut-offs of normal IMT. Results: CatK levels were similar in Ktx recipients and healthy subjects but significantly reduced as compared to HD (p = 0.0001). In Ktx, at multivariate analyses CatK was associated with the LV end-diastolic volume (LVEDVi) ( ß = 0.514; p = 0.05), Ktx vintage ( ß = -0.333; p = 0.05) and mean IMT ( ß = -0.545; p = 0.05); this latter robust inverse association was confirmed also in another multivariate model with IMT as the dependent variable. Logistic regression analyses confirmed the beneficial meaning of CatK increase towards subclinical atherosclerosis [Odds Ratio (OR) 0.761; 95% Confidence Interval (CI) 0.569-0.918, p = 0.04]. At Receiver Operating Characteristics (ROC) analyses, CatK held a remarkable discriminatory power in identifying Ktx patients with abnormally increased IMT [Area Under the Curve (AUC) 0.763; 95% CI 0.601-0.926; p = 0.001]). Conclusions: In Ktx recipients, reduced CatK levels reflect the time-dependent improvement in the uremic milieu, cardiac adaptations and, above all, the severity of subclinical atherosclerosis. CatK measurement in Ktx may therefore hold significance for improving early CV risk stratification.

Circulating Omentin-1, Sustained Inflammation and Hyperphosphatemia at the Interface of Subclinical Atherosclerosis in Chronic Kidney Disease Patients on Chronic Renal Replacement Therapy.

Background and Objectives: Subclinical atherosclerosis, reflected by abnormal carotid intima-media thickness (cIMT), is pervasive among chronic kidney disease patients on chronic renal replacement therapy (RRT), being mostly influenced by uremia-related rather than traditional risk factors. Materials and Methods: In this pilot study, we measured circulating levels of Omentin-1, a recently discovered adipokine with strong anti-atherogenic properties, in a heterogeneous cohort of 77 asymptomatic RRT individuals (40 chronic kidney transplant recipients, Ktx; and 37 chronic hemodialysis patients, HD) and in 30 age-matched controls. Results: Omentin-1 was increased in RRT individuals as compared with controls (p = 0.03). When stratifying for renal replacement modality, we found Ktx patients to have significantly lower Omentin-1 than HD patients (p = 0.01). Lower Omentin-1 levels were also found among RRT individuals with pathological cIMT (168.7 [51.1-457.8] vs. 474.9 [197.2-1432.1]; p = 0.004). Our multivariate correlations analysis revealed Omentin-1 as the most robust independent predictor of carotid atherosclerosis (ß-0.687; p = 0.03), even more than total cholesterol, diastolic BP and age, and this adipokine was at the crossroad of a complex interplay with sustained inflammation (high CRP and ferritin) and hyperphosphatemia in predicting higher cIMT values. Conclusion: The findings reported extend to renal patients with advanced disease, with the possible involvement of Omentin-1 in the pathogenesis of atherosclerosis. This may set the stage for future interventional studies of Omentin-1 replacement to retard atherosclerosis progression, as it is currently being investigated in other disease settings.

Altered circulating marinobufagenin levels and recurrent intradialytic hypotensive episodes in chronic hemodialysis patients: a pilot, prospective study.

Intradialytic hypotension (IDH) is a sudden and often serious complication of chronic hemodialysis (HD). In this prospective study, we aimed at evaluating the clinical predictors of IDH in a homogeneous cohort of chronic HD patients, with a particular focus on marinobufagenin (MBG), an endogenous cardiotonic steroid which alterations have previously been involved in various cardiovascular disorders. MBG levels in HD patients were significantly higher than in controls (p = 0.03), remained unchanged throughout a single HD session and were not correlated with the absolute or partial fluid loss achieved. During a 30-day follow-up, 19 patients (65.5%) experienced at least one IDH (73 total episodes). An inverse correlation was found between baseline MBG and the number of IDH (R = -0.55; p = 0.001). HD patients experiencing IDH presented remarkably lower baseline MBG as compared to others (p = 0.008) with a statistically significant trend during HD (p = 0.02). At Kaplan-Meier analyses, HD patients with lower MBG manifested a four-to-six fold increased risk of IDH during follow-up (crude Hazard Ratio ranging from 4.37 to 6.68). At Cox regression analyses, MBG measurement at different time points resulted the strongest time-dependent predictors of IDH among all the variables considered (HR ranging from 0.068 to 0.155; p: 0.002 to <0.0001). Findings obtained suggest that differently altered MBG in chronic HD patients may reflect a diverse vascular and hemodynamic tolerance to HD stress, eventually leading to recurrent IDH episodes. Further studies are needed to confirm the prognostic capacity of MBG for identifying HD patients at high risk of IDH, particularly those with apparently optimal fluid status.

Baseline chest X-ray in coronavirus disease 19 (COVID-19) patients: association with clinical and laboratory data.

PURPOSE: To assess the reliability of CXR and to describe CXR findings and clinical and laboratory characteristics associated with positive and negative CXR. METHODS: Retrospective two-center study on consecutive patients admitted to the emergency department of two north-western Italian hospitals in March 2020 with clinical suspicion of COVID-19 confirmed by RT-PCR and who underwent CXR within 24 h of the swab execution. 260 patients (61% male, 62.8 ± 15.8 year) were enrolled. CXRs were rated as positive (CXR+) or negative (CXR-), and features reported included presence and distribution of airspace opacities, pleural effusion and reduction in lung volumes. Clinical and laboratory data were collected. Statistical analysis was performed with nonparametric tests, binary logistic regression (BLR) and ROC curve analysis. RESULTS: Sensitivity of CXR was 61.1% (95%CI 55-67%) with a typical presence of bilateral (62.3%) airspace opacification, more often with a lower zone (88.7%) and peripheral (43.4%) distribution. At univariate analysis, several factors were found to differ significantly between CXR+ and CXR-. The BLR confirmed as significant predictors only lactate dehydrogenase (LDH), C-reactive protein (CRP) and interval between the onset of symptoms and the execution of CXR. The ROC curve procedure determined that CRX+ was associated with LDH > 500 UI/L (AUC = 0.878), CRP > 30 mg/L (AUC = 0.830) and interval between the onset of symptoms and the execution of CXR > 4 days (AUC = 0.75). The presence of two out of three of the above-mentioned predictors resulted in CXR+ in 92.5% of cases, whereas their absence in 7.4%. CONCLUSION: CXR has a low sensitivity. LDH, CRP and interval between the onset of symptoms and the execution of CXR are major predictors for a positive CXR.

Microenvironment Molecular Profile Combining Glycation Adducts and Cytokines Patterns on Secretome of Short-term Blood-derived Cultures during Tumour Progression.

Cancer cells are known to secrete many bioactive factors acting both with paracrine and autocrine mechanisms by which they condition the surrounding microenvironment. At the same time, the intracytoplasmic metabolic activities microenvironment influences the profile of this secretion. It is well known that cancer cells exhibit prevalent glycolytic metabolism and a more oxidative atmosphere compared to their healthy counterparts; this metabolic phenotype promotes glycate adducts formation and secretion. Considering the exacerbation of metabolic changes during the cancer progression, it is suggestive to explore the potential correlation between the increasing rate of glycan adducts and the specific pattern of secreted cytokines in different phases of cancer disease. We analyzed the secretomes of blood-derived cancer cell cultures from cancer patients and healthy subjects. The relative glycate adducts content in cancer secretomes was higher in comparison to that of healthy samples. Moreover, the stratification based on different phases of cancer disease correlated with a specific cytokines panel. The results obtained open a new perspective of observation of the intricate relationship between metabolome and inflammation in cancer. By using the analysis of secretome combined with a standardized protocol of liquid biopsy, it would be possible to identify specific profiles of molecular markers useful to arrange alternative and personalized medicine strategies.

Deep Submicron EGFET Based on Transistor Association Technique for Chemical Sensing.

Extended-gate field-effect transistor (EGFET) is an electronic interface originally developed as a substitute for an ion-sensitive field-effect transistor (ISFET). Although the literature shows that commercial off-the-shelf components are widely used for biosensor fabrication, studies on electronic interfaces are still scarce (e.g., noise processes, scaling). Therefore, the incorporation of a custom EGFET can lead to biosensors with optimized performance. In this paper, the design and characterization of a transistor association (TA)-based EGFET was investigated. Prototypes were manufactured using a 130 nm standard complementary metal-oxide semiconductor (CMOS) process and compared with devices presented in recent literature. A DC equivalence with the counterpart involving a single equivalent transistor was observed. Experimental results showed a power consumption of 24.99 mW at 1.2 V supply voltage with a minimum die area of 0.685 × 1.2 mm². The higher aspect ratio devices required a proportionally increased die area and power consumption. Conversely, the input-referred noise showed an opposite trend with a minimum of 176.4 nVrms over the 0.1 to 10 Hz frequency band for a higher aspect ratio. EGFET as a pH sensor presented further validation of the design with an average voltage sensitivity of 50.3 mV/pH, a maximum current sensitivity of 15.71 mA1/2/pH, a linearity higher than 99.9%, and the possibility of operating at a lower noise level with a compact design and a low complexity.

EGFET-Based Sensors for Bioanalytical Applications: A Review.

Since the 1970s, a great deal of attention has been paid to the development of semiconductor-based biosensors because of the numerous advantages they offer, including high sensitivity, faster response time, miniaturization, and low-cost manufacturing for quick biospecific analysis with reusable features. Commercial biosensors have become highly desirable in the fields of medicine, food, and environmental monitoring as well as military applications, whereas increasing concerns about food safety and health issues have resulted in the introduction of novel legislative standards for these sensors. Numerous devices have been developed for monitoring biological processes such as nucleic acid hybridization, protein⁻protein interaction, antigen⁻antibody bonds, and substrate⁻enzyme reactions, just to name a few. Since the 1980s, scientific interest moved to the development of semiconductor-based devices, which also include integrated front-end electronics, such as the extended-gate field-effect transistor (EGFET) biosensor, one of the first miniaturized chemical sensors. This work is intended to be a review of the state of the art focused on the development of biosensors and chemosensors based on extended-gate field-effect transistor within the field of bioanalytical applications, which will highlight the most recent research reported in the literature. Moreover, a comparison among the diverse EGFET devices will be presented, giving particular attention to the materials and technologies.

Impact of legumes and plant proteins consumption on cognitive performances in the elderly.

BACKGROUND: Numerous studies have investigated the role of the dietary factors in the prevention of cognitive decline but the short-term effects of foods choice on cognitive performances in the elderly are poorly explored. Our aim was to investigate the choice of foods among elderly Italian individuals and the association with cognitive function. METHODS: In this longitudinal study, the participants were 214 individuals aged ≥65 years with a score >20 at the Mini Mental State Examination. The cognitive sub-test of ADAScale was used to detect cognitive decline progression over 12 months. Food choices was measured by a combination of a 24-h recall and a seven-day diet record and Principal Components Analysis. RESULTS: The Principal Components Analysis identified four food and four nutrient patterns. MMSE and ADAS-cog score after 1 year were found to be associated with legumes pattern (B = 0.25, p = 0.007; 95% CI 0.07/0.44; and B = -0.10, p = 0.006; CI -0.79/-0.30, respectively). A dietary pattern including plant proteins was independently associated with an improved ADAS-cog after 1 year (B = 0.584, p = 0.04; OR 1.79, CI 0.04-0.42). CONCLUSIONS: The Principal Components Analysis is useful to investigate the choice of foods and nutrients in the elderly. We demonstrated an association between legumes pattern with cognitive performances.

The correct renal function evaluation in patients with thyroid dysfunction.

Thyroid dysfunction induces several renal derangements involving all nephron portions. Furthermore, dysthyroidism is a recognized risk factor associated with the development of chronic kidney disease. Current data, in fact, demonstrate that either subclinical or overt thyroid disease is associated with significant changes in creatinine, estimated glomerular filtration rate, measured glomerular filtration rate and Cystatin C. Herein, we systematically reviewed several relevant studies aiming at the identification of the most sensitive and specific parameter for the correct renal function evaluation in patients with thyroid dysfunction, that are usually treated as outpatients. Our systematic review indicates that estimated glomerular filtration rate, preferably with CKD-EPI equation, appears to be the most reliable and wieldy renal function parameter. Instead, Cystatin C should be better used in the grading of thyroid dysfunction severity.

Elevations of inflammatory markers PTX3 and sST2 after resuscitation from cardiac arrest are associated with multiple organ dysfunction syndrome and early death.

BACKGROUND: A systemic inflammatory response is observed after cardiopulmonary resuscitation. We investigated two novel inflammatory markers, pentraxin 3 (PTX3) and soluble suppression of tumorigenicity 2 (sST2), in comparison with the classic high-sensitivity C-reactive protein (hsCRP), for prediction of early multiple organ dysfunction syndrome (MODS), early death, and long-term outcome after out-of-hospital cardiac arrest. METHODS: PTX3, sST2, and hsCRP were assayed at ICU admission and 48 h later in 278 patients. MODS was defined as the 24 h non-neurological Sequential Organ Failure Assessment (SOFA) score ≥ 12. Intensive care unit (ICU) death and 12-month Cerebral Performance Category (CPC) were evaluated. RESULTS: In total, 82% of patients survived to ICU discharge and 48% had favorable neurological outcome at 1 year (CPC 1 or 2). At ICU admission, median plasma levels of hsCRP (2.8 mg/L) were normal, while levels of PTX3 (19.1 ng/mL) and sST2 (117 ng/mL) were markedly elevated. PTX3 and sST2 were higher in patients who developed MODS (p<0.0001). Admission levels of PTX3 and sST2 were also higher in patients who died in ICU and in those with an unfavorable 12-month neurological outcome (p<0.01). Admission levels of PTX3 and sST2 were independently associated with subsequent MODS [OR: 1.717 (1.221-2.414) and 1.340, (1.001-1.792), respectively] and with ICU death [OR: 1.536 (1.078-2.187) and 1.452 (1.064-1.981), respectively]. At 48 h, only sST2 and hsCRP were independently associated with ICU death. CONCLUSIONS: Higher plasma levels of PTX3 and sST2, but not of hsCRP, at ICU admission were associated with higher risk of MODS and early death.

New laboratory markers for the management of rheumatoid arthritis patients.

Rheumatoid arthritis, the most prominent of systemic autoimmune rheumatic diseases, represents an important social health problem. Recent insights into the immunopathogenic mechanism of this complex and multiform illness might open new perspectives for a more appropriate laboratory approach. In this review we focus on the most relevant pathogenetic mechanism; indicating the laboratory biomarkers specifically linked to early diagnosis, prognosis, evolutive aspects of the disease, and therapeutic efficacy. Evidence based on laboratory medicine could provide the best outcome for patients.

Early effects of a hypocaloric, Mediterranean diet on laboratory parameters in obese individuals.

Calorie restriction is a common strategy for weight loss in obese individuals. However, little is known about the impact of moderate hypocaloric diets on obesity-related laboratory parameters in a short-term period. Aim of this study was to evaluate the variation of laboratory biomarkers in obese individuals following a Mediterranean, hypocaloric (1400-1600 Kcal/die) diet. 23 obese, pharmacologically untreated patients were enrolled and subjected to the determination of anthropometric variables and blood collection at baseline, 1 and 4 months after diet initiation. After 4 months of calorie restriction, we observed a significant decrease in body weight and BMI (both P < 0.0001), insulin (P = 0.037), HOMA-IR (P = 0.026), leptin (P = 0.008), and LDH (P = 0.023) and an increase in EGF (P = 0.013). All these parameters, except LDH, varied significantly already at 1 month after diet initiation. Also, lower levels of insulin (P = 0.025), leptin (P = 0.023), and EGF (P = 0.035) were associated with a greater (>5%) weight loss. Collectively, our data support a precocious improvement of insulin and leptin sensitivity after a modest calorie restriction and weight reduction. Moreover, EGF and LDH may represent novel markers of obesity, which deserve further investigations.

Coexistence of Hashimoto's Thyroiditis in Differentiated Thyroid Cancer: Post-Operative Monitoring of Anti-Thyroglobulin Antibodies and Assessment of Treatment Response.

INTRODUCTION: Differentiated thyroid carcinoma (DTC) is frequently found in conjunction with autoimmune thyroid disorders, particularly Hashimoto's thyroiditis (HT). This study investigates the impact of coexisting HT on the persistence of an indeterminate response to therapy due to positive anti-thyroglobulin antibodies (AbTg), measured via competitive immunoassay, in a consecutive patient series from Calabria, Southern Italy. METHODS: This retrospective longitudinal study analyzed 259 consecutive DTC patients managed at the Endocrinology Unit of Renato Dulbecco Hospital (Catanzaro, Italy) up to 2023. Patients with medullary and undifferentiated thyroid carcinoma, partial thyroidectomy, less than six months of post-operative monitoring, or missing clinical data were excluded. Demographic information, histological findings, initial tumor stage, and ATA risk category were collected. The response to therapy was assessed based on ATA guidelines. RESULTS: Among the 259 patients, 29% had coexisting HT. Patients with HT exhibited distinct characteristics: a higher proportion of females (87.0% vs. 74.7%), a shorter post-operative monitoring duration (median 3 vs. 5 years), and a higher prevalence of papillary thyroid carcinoma (PTC) (97.4% vs. 86.3%). The tumor size, lymph node involvement, and distant metastasis were similar between the groups, with patients without HT having a higher incidence of extrathyroidal tumor extension. However, the initial TNM stage and ATA risk category did not differ significantly. At the six-month follow-up, HT patients showed a higher rate of indeterminate responses, primarily due to positive AbTg. After 12 months, the response categories aligned, with decreasing AbTg levels in the HT group. After 24 months, most patients with long-term follow-up demonstrated an excellent response to DTC therapy, irrespective of HT coexistence. CONCLUSIONS: While HT does not worsen DTC prognosis, it may result in indeterminate responses. AbTg measurements in the peri-operative period should be encouraged to facilitate post-operative monitoring, emphasizing the importance of using standardized assays. Further research in larger populations with extended follow-up is needed to comprehensively understand the HT-DTC relationship.

Maternal Preconception Body Mass Index Overtakes Age as a Risk Factor for Gestational Diabetes Mellitus.

Introduction-The purpose of this study was to determine the relative impact of modifiable and non-modifiable risk factors in the development of gestational diabetes mellitus (GDM), with a particular focus on maternal preconception body mass index (BMI) and age, two important determinants of insulin resistance. Understanding the factors that contribute most to the current escalation of GDM rates in pregnant women could help to inform prevention and intervention strategies, particularly in areas where this female endocrine disorder has an elevated prevalence. Methods-A retrospective, contemporary, large population of singleton pregnant women from southern Italy who underwent 75 g OGTT for GDM screening was enrolled at the Endocrinology Unit, "Pugliese Ciaccio" Hospital, Catanzaro. Relevant clinical data were collected, and the characteristics of women diagnosed with GDM or with normal glucose tolerance were compared. The effect estimates of maternal preconception BMI and age as risk factors for GDM development were calculated through correlation and logistic regression analysis by adjusting for potential confounders. Results-Out of the 3856 women enrolled, 885 (23.0%) were diagnosed with GDM as per IADPSG criteria. Advanced maternal age (≥35 years), gravidity, reproductive history of spontaneous abortion(s), previous GDM, and thyroid and thrombophilic diseases, all emerged as non-modifiable risk factors of GDM, whereas preconception overweight or obesity was the sole potentially modifiable risk factor among those investigated. Maternal preconception BMI, but not age, had a moderate positive association with fasting glucose levels at the time of 75 g OGTT (Pearson coefficient: 0.245, p < 0.001). Abnormalities in fasting glucose drove the majority (60%) of the GDM diagnoses in this study. Maternal preconception obesity almost tripled the risk of developing GDM, but even being overweight resulted in a more pronounced increased risk of developing GDM than advanced maternal age (adjusted OR for preconception overweight: 1.63, 95% CI 1.320-2.019; adjusted OR for advanced maternal age: 1.45, 95% CI 1.184-1.776). Conclusions-Excess body weight prior to conception leads to more detrimental metabolic effects than advanced maternal age in pregnant women with GDM. Thus, in areas in which GDM is particularly common, such as southern Italy, measures aiming to counteracting maternal preconception overweight and obesity may be efficient in reducing GDM prevalence.

Marinobufagenin, Left Ventricular Hypertrophy and Residual Renal Function in Kidney Transplant Recipients.

BACKGROUND: Left ventricular hypertrophy (LVH), which is a pervasive complication of end-stage kidney disease (ESKD), persists in some uremic individuals even after kidney transplantation (Ktx), contributing to worsening CV outcomes. Marinobufagenin (MBG), an endogenous steroid cardiotonic hormone endowed with natriuretic and vasoconstrictive properties, is an acknowledged trigger of uremic cardiomyopathy. However, its clinical significance in the setting of Ktx remains undefined. METHODS: In a cohort of chronic Ktx recipients (n = 40), we assessed circulating MBG together with a thorough clinical and echocardiographic examination. Forty matched haemodialysis (HD) patients and thirty healthy subjects served as controls for MBG measurements. Patients were then prospectively followed up to 12 months and the occurrence of an established cardio-renal endpoint (death, CV events, renal events, graft rejection) was recorded. RESULTS: Median MBG plasma levels were lower in Ktx as compared with HD patients (p = 0.02), but higher as compared with healthy controls (p = 0.0005). Urinary sodium (ß = 0.423; p = 0.01) and eGFR (ß = -0.324; p = 0.02) were the sole independent predictors of MBG in this cohort, while a strong correlation with left ventricular mass index (LVMi), found in univariate analyses (R = 0.543; p = 0.0007), gained significance only in multivariate models not including eGFR. Logistic regression analyses indicated MBG as a significant predictor of the combined endpoint (OR 2.38 [1.10-5.12] per each 1 nmoL/L increase; p = 0.01), as well as eGFR, LVMi, serum phosphate and proteinuria. CONCLUSIONS: Ktx recipients display altered MBG levels which are influenced by sodium balance, renal impairment and the severity of LVH. Thus, MBG might represent an important missing link between reduced graft function and pathological cardiac remodelling and may hold important prognostic value for improving cardio-renal risk assessment.

Does NUCB2/Nesfatin-1 Influence Eating Behaviors in Obese Patients with Binge Eating Disorder? Toward a Neurobiological Pathway.

Nesfatin-1 is a new anorexigenic neuropeptide involved in the regulation of hunger/satiety, eating, and affective disorders. We aimed to investigate nesfatin-1 secretion in vitro, in murine adipose cells, and in human adipose fat samples, as well as to assess the link between circulating nesfatin-1 levels, NUCB2 and Fat Mass and Obesity Gene (FTO) polymorphisms, BMI, Eating Disorders (EDs), and pathological behaviors. Nesfatin-1 secretion was evaluated both in normoxic fully differentiated 3T3-L1 mouse adipocytes and after incubation under hypoxic conditions for 24 h. Omental Visceral Adipose tissue (VAT) specimens of 11 obese subjects, and nesfatin-1 serum levels' evaluation, eating behaviors, NUCB2 rs757081, and FTO rs9939609 polymorphisms of 71 outpatients seeking treatment for EDs with different Body Mass Index (BMI) were studied. Significantly higher levels of nesfatin-1 were detected in hypoxic 3T3-L1 cultured adipocytes compared to normoxic ones. Nesfatin-1 was highly detectable in the VAT of obese compared to normal-weight subjects. Nesfatin-1 serum levels did not vary according to BMI, sex, and EDs diagnosis, but correlations with grazing; emotional, sweet, and binge eating; hyperphagia; social eating; childhood obesity were evident. Obese subjects with CG genotype NUCB2 rs757081 and AT genotype FTO rs9939609 polymorphisms had higher nesfatin-1 levels. It could represent a new biomarker of EDs comorbidity among obese patients.