Giuseppe Campagna

Prospective Study of Effectiveness of Ultrasound-Guided Radiofrequency Ablation Versus Control Group in Patients Affected by Benign Thyroid Nodules

CONTEXT Ultrasound-guided radiofrequency ablation (RFA) of solid thyroid nodules (TNs) is a minimally invasive procedure that may induce a volume reduction of symptomatic solid benign TNs. OBJECTIVE The aim of the study was to evaluate the effectiveness and safety of RFA in debulking benign TNs. DESIGN AND PATIENTS Eighty-four consecutive patients with symptomatic and cytologically benign solid nodules were randomly assigned to either a single RFA session (group A; n = 42) or follow-up (group B; n = 42) at our center. Entry criteria were a solid thyroid nodule or predominantly solid (with a fluid component ≤ 30% of the volume), normal thyroid function, no autoimmunity, and no previous thyroid gland treatment. Three subgroups were formed according to the baseline volume of nodules: small (≤ 12 mL), medium (from 12 to 30 mL), or large (>30 mL). METHODS In group A RFA was performed in a single session with the moving-shot technique. Volume and local symptom changes were evaluated 1 and 6 months after RFA. RESULTS In group A, the volume decreased from 24.5.5 ± 19.6 to 8.6 ± 9.5 6 months after RFA (P = .001). The greatest volume reduction was in small nodules. The pressure symptom score improved only in medium and large nodules (P < .001), whereas the cosmetic score improved in all treated patients (P < .001). The rate of thyroid volumetric reduction was not statistically different between solid and predominantly solid nodules. Only one patient experienced permanent right paramedian vocal cord palsy with inspiratory stridor without dysphonia. In group B, nodule volume remained unchanged, whereas the symptom score was worse at the 6-month evaluation (P = .01). CONCLUSIONS RFA is effective in reducing thyroid nodule volume. The best reduction rate was observed in small TNs. The thyroid volumetric reduction does not change according to the sonographic features. The mean treatment duration was longer in larger TNs.

GADA Titer-Related Risk for Organ-Specific Autoimmunity in LADA Subjects Subdivided according to Gender (NIRAD Study 6)

CONTEXT Latent autoimmune diabetes in adults (LADA) includes a heterogeneous population wherein, based on glutamic acid decarboxylase antibody (GADA) titer, different subgroups of subjects can be identified. OBJECTIVE The aim of the present study was to evaluate GADA titer-related risk for β-cell and other organ-specific autoimmunity in LADA subjects. METHODS Adult-onset autoimmune diabetes subjects (n=236) and type 2 diabetes (T2DM) subjects (n=450) were characterized for protein tyrosine phosphatase (IA-2IC and IA-2(256-760)), zinc transporter 8 (ZnT8), thyroid peroxidase, (TPO), steroid 21-hydroxylase (21-OH), tissue transglutaminase (tTG), and antiparietal cell (APC) antibodies. RESULTS High GADA titer compared to low GADA titer showed a significantly higher prevalence of IA-2IC, IA-2(256-760), ZnT8, TPO, and APC antibodies (P≤0.04 for all comparison). 21-OH antibodies were detected in 3.4% of high GADA titer. A significant decreasing trend was observed from high GADA to low GADA and to T2DM subjects for IA-2(256-760), ZnT8, TPO, tTG, and APC antibodies (P for trend≤0.001). TPO was the only antibody showing a different prevalence between gender; low GADA titer and T2DM female patients had a higher frequency of TPO antibody compared to males (P=0.0004 and P=0.0006, respectively), where the presence of high GADA titer conferred an odds ratio of 8.6 for TPO compared to low GADA titer. After subdividing high and low GADA titer subjects according to the number of antibodies, we observed that 73.3% of high GADA titer subjects were positive for at least one or more antibodies, compared to 38.3% of low GADA titer (P<0.0001). CONCLUSIONS In LADA subjects, high GADA titer was associated with a profile of more severe autoimmunity and, in male gender, specifically predisposed to thyroid autoimmunity. A regular screening for other antibodies is recommended in LADA patients according to GADA titer and gender.

High GADA titer increases the risk of insulin requirement in LADA patients: a 7-year follow-up (NIRAD study 7)

OBJECTIVE The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up. METHODS This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression. RESULTS During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes (P<0.0001 for both). A BMI of ≤25 kg/m2 and IA-2IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (P<0.0001 for both). The proportion of LADA patients requiring insulin was significantly higher in the group of subjects treated also with sulfonylurea in the first year from diagnosis compared with those treated with diet and/or insulin sensitizers (P<0.001). The multivariate analysis confirmed that the presence of high GADA titer was a significant predictor of insulin requirement (P<0.0001, OR=6.95). CONCLUSIONS High GADA titer, BMI ≤ 25, ZnT8 and IA-2IC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients.

Tyrosine Phosphatase–Related Islet Antigen 2(256–760) Autoantibodies, the Only Marker of Islet Autoimmunity That Increases by Increasing the Degree of BMI in Obese Subjects With Type 2 Diabetes

OBJECTIVE Since patients with type 2 diabetes and positive for type 1 diabetes–specific antibodies have wide variations in BMI, this study evaluated whether the frequency and pattern of islet autoantibody positivity is related to BMI. RESEARCH DESIGN AND METHODS Clinical and biochemical characteristics and islet autoantibodies including GAD and protein tyrosine phosphatases islet antigen-2 (IA-2)IC and IA-2(256–760) were evaluated in 1,850 patients with type 2 diabetes from the Non–Insulin Requiring Autoimmune Diabetes study cohort. BMI was evaluated in all patients, who were then subdivided in three groups according to BMI (<25, ≥25 to <30, and ≥30 kg/m2). RESULTS Out of 1,850, 120 (6.5%) patients were positive for at least one of the following antibodies: GAD (4.1%), IA-2(256–760) (3.3%), or IA-2IC (1.1%). GAD and IA-2IC antibodies showed decreasing frequencies with increasing BMI (P < 0.0001 and 0.0006, respectively, for trend); in contrast, the frequency of IA-2(256–760) antibodies increased with increasing BMI (P = 0.005 for trend). Patients with type 2 diabetes positive for IA-2(256–760) alone showed a phenotype resembling classical obese type 2 diabetes, with higher BMI, waist circumference, and uric acid (P < 0.005 for all), lower thyroid peroxidase antibodies, and lower progression to insulin requirement than GAD antibody–positive patients (P = 0.04 and P = 0.0005, respectively). CONCLUSIONS The IA-2(256–760) antibody appears to represent an antibody marker that mainly identifies a clinical phenotype very similar to obese type 2 diabetes, suggesting a possible different pathogenetic mechanism.

Serum Sclerostin and Bone Turnover in Latent Autoimmune Diabetes in Adults

Purpose Bone formation is impaired in both type 1 diabetes and type 2 diabetes (T2D), whereas sclerostin, an antagonist of bone formation, is increased in T2D only. No data are available on latent autoimmune diabetes in adults (LADA), an autoimmune type of diabetes that may clinically resemble T2D at diagnosis. We evaluated serum sclerostin and bone turnover markers in LADA compared with those in T2D and whether metabolic syndrome (MetS) affects sclerostin in T2D or LADA. Methods This cross-sectional study included 98 patients with T2D and 89 with LADA from the Action LADA and Non Insulin Requiring Autoimmune Diabetes cohorts. Patients were further divided according to MetS status. Nondiabetic participants (n = 53) were used as controls. Serum sclerostin, bone formation (pro-collagen type 1 N-terminal propeptide [P1NP]), and bone resorption (C-terminal telopeptide of type I collagen [CTX]) were analyzed. Results Patients with T2D had higher sclerostin than did those with LADA [P = 0.0008, adjusted for sex and body mass index (BMI)], even when analysis was restricted to patients with MetS (adjusted P = 0.03). Analysis of T2D and LADA groups separately showed that sclerostin was similar between those with and those without MetS. However, a positive trend between sclerostin and number of MetS features was seen with T2D (P for trend = 0.001) but not with LADA. Patients with T2D or LADA had lower CTX than did controls (P = 0.0003) and did not have significantly reduced P1NP. Sclerostin was unrelated to age or hemoglobin A1c but was correlated with BMI (ρ = 0.29; P = 0.0001), high-density lipoprotein (ρ = -0.23; P = 0.003), triglycerides (ρ = 0.19; P = 0.002), and time since diagnosis (ρ = 0.32; P < 0.0001). Conclusions Patients with LADA presented lower bone resorption than did controls, similar to patients with T2D. Sclerostin is increased in T2D but not in LADA, suggesting possible roles on bone metabolism in T2D only.

Excellent Intra and Inter-Observer Reproducibility of Wrist Circumference Measurements in Obese Children and Adolescents.

In a previous study, we found that wrist circumference, in particular its bone component, was associated with insulin resistance in a population of overweight/obese children. The aim of the present study was to evaluate the intra- and inter-operator variability in wrist circumference measurement in a population of obese children and adolescents. One hundred and two (54 male and 48 female) obese children and adolescents were consecutively enrolled. In all subjects wrist circumferences were measured by two different operators two times to assess intra- and inter-operator variability. Statistical analysis was performed using SAS v.9.4 and JMP v.12. Measurements of wrist circumference showed excellent inter-operator reliability with Intra class Correlation Coefficients (ICC) of 0.96 and ICC of 0.97 for the first and the second measurement, respectively. The intra-operator reliability was, also, very strong with a Concordance Correlation Coefficient (CCC) of 0.98 for both operators. The high reproducibility demonstrated in our results suggests that wrist circumference measurement, being safe, non-invasive and repeatable can be easily used in out-patient settings to identify youths with increased risk of insulin-resistance. This can avoid testing the entire population of overweight/obese children for insulin resistance parameters.

Temporal Trends of HLA, CTLA-4 and PTPN22 Genotype Frequencies among Type 1 Diabetes in Continental Italy

The incidence of type 1 diabetes has, progressively, increased worldwide over the last decades and also in Continental Italian population. Previous studies performed in northern European countries, showed, alongside a general increase in the disease incidence, a decreasing frequency of the highest risk HLA genotype in type 1 diabetes populations, thus emphasizing the role of environmental factors. The aim of the study was to evaluate whether a decreasing trend of high risk HLA, CTLA-4 and PTPN22 genotypes would be present in type 1 diabetes subjects of Continental Italy, a country considered at low incidence of the disease compared to northern European populations. N = 765 type 1 diabetes patients diagnosed from 1980 to 2012 in Lazio region were included. For HLA, CTLA4 and PTPN22 temporal trend evaluation, subjects were subdivided into groups of years according to age at diagnosis. All subjects were typed for HLA-DRB1 and DQB1 by a reverse line blot. The CT60 polymorphism of the CTLA4 and C1858T of the PTPN22 gene were genotyped using ABI PRISM 7900HT (n = 419 and n = 364 respectively). HLA genotypes were divided in high, moderate and low risk categories. The proportion of the HLA risk categories was not statistically different over the three decades in subjects with age of onset <15 years and ≥15 years. The genotype distribution of CT60 polymorphism of CTLA4 gene did not show any change in the frequencies during time. The analysis of the PTPN22 C1858T variant revealed, instead, that the frequency of CT+TT susceptibility genotypes decreased during time (23.9% vs 13.6%, p = 0.017). We can hypothesize that the pressure of the diabetogenic environment could be milder and therefore not sufficient to reduce the need of a strong genetic background (HLA) “to precipitate” diabetes; the increased pressure of the environment could have, instead, some effects on minor susceptibility genes in our population.

Probiotic supplementation in trained trotter horses: effect on blood clinical pathology data and urine metabolomic assessed in field

The attention of sports community toward probiotic supplementation as a way to promote exercise and training performance, together with good health, has increased in recent years. This has applied also to horses, with promising results. Here, for the first time, we tested a probiotic mix of several strains of live bacteria typically employed for humans to improve the training performance of Standardbred horses in athletic activity. To evaluate its effects on the horse performance, we measured lactate concentration in blood, a translational outcome largely employed for the purpose, combined with the study of hematological and biochemical parameters, together with urine from a metabolomics perspective. The results showed that the probiotic supplementation significantly reduced postexercise blood lactate concentration. The hematological and biochemical parameters, together with urine molecular profile, suggested that a likely mechanism underlying this positive effect was connected to a switch of energy source in muscle from carbohydrates to short-chain fatty acids. Three sulfur-containing molecules differently concentrated in urines in connection to probiotics administration suggested that such switch was linked to sulfur metabolism. NEW & NOTEWORTHY Probiotic supplementation could reduce postexercise blood lactate concentration in Standardbred horses in athletic activity. Blood parameters, together with urine molecular profile, suggest the mechanism underlying this positive effect is connected to a switch of energy source in muscle from carbohydrates to short-chain fatty acids. Sulfur-containing molecules found in urines in connection to probiotics administration suggested that such switch was linked to sulfur metabolism.

Wrist circumference is associated with increased systolic blood pressure in children with overweight/obesity

Wrist circumference is a clinical marker for insulin-resistance in overweight/obese children and adolescents. Insulin resistance is considered a major determinant of increased vascular resistance and hypertension. The aim of the study was to investigate the association between wrist circumference and systolic (S) and diastolic (D) blood pressure (BP) in a population of overweight/obese children and adolescents. A population of 1133 overweight/obese children and adolescents (n = 1133) were consecutively enrolled. Multivariate regression analyses were used to investigate the influence of independent variables on the variance of BP. The prevalence of hypertension was 21.74% in males and 28.95% in females (p = 0.048). The results showed that SBP was significantly associated with wrist circumference in both genders (p < 0.0001 for both comparisons). We found no association between DBP and wrist circumference in either gender. Wrist circumference accounted for 17% of the total variance of SBP in males and 14% in females. Wrist circumference, a marker of insulin resistance, is associated with increased SBP in overweight/obese children and adolescents, suggesting a role of insulin resistance in the pathogenesis and development of hypertension.

Efficacy and safety of a single radiofrequency ablation of solid benign non-functioning thyroid nodules

Objective The objective of our study is to evaluate the clinical outcomes and safety of radiofrequency thermal ablation (RFA) for benign thyroid nodules (BTNs) over a 1-year follow-up. Subjects and methods This is a monocentric retrospective study. Forty-eight patients with solid, non-functioning BTNs were treated by RFA using a 17G internally cooled electrode. We categorized thyroid nodules as small (≤ 12 mL), medium (12 to 30 mL), or large (over 30 mL). BTNs volume reduction, thyroid function, cosmetic and compressive score changes and side effect evaluation at 6 and 12 months were evaluated. Results BTN volume decreased significantly from baseline to 6 (mean percentage decrease of BTN volume was 66.8 ± 13.6%, p < 0.001). At 12 months, the mean percentage reduction of BTN volume compared to six months was 13.7 ± 17.1% (p < 0.001). At 6-month, symptom score had improved significantly (p < 0.001) while it does not change significantly between 6 and 12 months. In particular, symptom score improved significantly in the medium (p < 0.001) and large (p < 0.01) subgroups. Cosmetic score improved significantly between baseline and 6 months (p < 0.001) and between 6 and 12 months (p < 0.01). In all the subgroups, cosmetic score improved significantly between baseline and 6 months, while between 6 and 12 months it improved significantly only in the large group (p < 0.05). RFA was well tolerated. Only one patient experienced permanent right paramedian vocal cord palsy. Conclusions A single RFA treatment was effective in reducing BTNs volume, in particular small and medium nodules. Cosmetic score improved in all treated BTNs while symptom score only got better in the medium and large BTNs.