Tommaso Piticchio

Objective: Automated insulin delivery (AID) systems have significantly improved the management of type 1 diabetes (T1D), leading to better glycemic control and reduced hypoglycemia. However, older adults (≥ 65 years) remain underrepresented in clinical trials, and evidence specific to this population is limited. Design and patients: This narrative review synthesizes current evidence on the efficacy, safety, and usability of AID systems in older adults (≥ 65 years) with T1D. A comprehensive literature search of MEDLINE/PubMed was conducted using the PICO framework to identify relevant RCTs, observational studies, and systematic reviews, supplemented by literature studies on cognitive, functional, and psychosocial factors impacting technology adoption. Results: While data from randomized trials and meta-analyses in the general population consistently demonstrate improvements in time in range (TIR, 70–180 mg/dL) and reductions in hypoglycemia, evidence in older adults is still emerging. Frail individuals and those with multiple comorbidities are often underrepresented or excluded from current studies. Nevertheless, the available evidence suggests that many of these benefits are also maintained in older populations, particularly regarding hypoglycemia reduction. At the same time, factors such as cognitive impairment, functional limitations, caregiver dependence, and reduced digital literacy may affect the adoption and effective use of these technologies. Conclusions: AID systems appear effective and generally safe in selected older adults, with benefits in glycemic control and hypoglycemia reduction. However, given the marked heterogeneity of this population, further studies are needed to better define their role and applicability in routine clinical practice.

Diabetic gastroparesis (DGP) is a chronic and frequently underrecognized complication of diabetes mellitus, characterized by delayed gastric emptying in the absence of mechanical obstruction. It represents a clinically significant manifestation of diabetic autonomic neuropathy and arises from a complex interplay of sustained hyperglycemia, oxidative and nitrosative stress, advanced glycation end-product accumulation, impaired insulin/IGF-1 signaling, lipid dysmetabolism, and inflammatory activation. These mechanisms converge to damage autonomic and enteric neurons, reduce interstitial cells of Cajal density, and disrupt gastric smooth muscle function, ultimately leading to impaired and unpredictable gastric motility. Beyond gastrointestinal symptoms, DGP profoundly affects metabolic control. The altered timing and variability of gastric emptying disturb the physiological coordination between nutrient absorption and insulin pharmacokinetics, generating a temporal mismatch that predisposes patients to early postprandial hypoglycemia followed by late hyperglycemia. This pattern increases glycemic variability, complicates insulin dose adjustment, and contributes to oxidative stress and vascular risk. In this narrative review, we examine the current understanding of DGP pathophysiology and its clinical implications for insulin therapy. We discuss diagnostic strategies, nutritional interventions, and pharmacological treatments, with particular attention to insulin timing modulation. We also analyze the emerging role of diabetes technologies, including continuous glucose monitoring and automated insulin delivery systems, as well as future perspectives such as glucose-responsive insulins and regenerative approaches targeting gastric neuromuscular dysfunction. A mechanism-based, personalized therapeutic strategy may improve metabolic stability and patient outcomes.

Background: Pain may be absent in a substantial proportion of elderly patients with acute abdominal conditions. This study explored the association between type 2 diabetes mellitus (T2DM) and asymptomatic presentation. Methods: We conducted a cross-sectional analysis of 215 patients aged ≥ 65 years admitted with acute abdominal conditions. Demographic, clinical, and laboratory data were extracted from medical records. Descriptive statistics and multivariable logistic regression were used to identify associative predictors of asymptomatic acute abdomen (AAA). Results: The median age was 82 years [77–86]; 54.4% ( n = 117) were female; 31.2% ( n = 67) had T2DM. Overall, 33.5% ( n = 72) presented without abdominal pain. T2DM prevalence was higher in AAA than symptomatic patients (44.4% vs. 24.5%, p < 0.01). In multivariable analysis, T2DM (OR 1.95, 95% CI 1.10–3.45, p = 0.02), lower heart rate (OR 0.83, 95% CI 0.71–0.96, p = 0.01), and absence of fever (OR 0.50, 95% CI 0.26–0.95, p = 0.03) were associated with AAA. Among patients with T2DM, longer diabetes duration (12.5 years [10.5–14.5] vs. 8.8 years [5.0–11.0]; p < 0.01) and higher HbA1c (8.2% [7.2–8.7] vs. 7.5% [6.8–7.6]; p = 0.02) were associated with asymptomatic presentation. Conclusions: Asymptomatic acute abdomen is common among elderly patients. Long-standing and poorly controlled T2DM is associated with absent pain. Prospective studies are needed to clarify causal mechanisms, and early glyco-metabolic assessment may aid recognition of at-risk patients.

Objective: Differentiated thyroid carcinoma (DTC) has an excellent prognosis, but recurrence remains a clinical concern, especially in intermediate‐risk patients. Current stratification systems focus primarily on tumor characteristics, overlooking the host's biological capacity to counteract tumor progression. To investigate this aspect, we assessed systemic inflammatory and nutritional status using hematological indices. The study aimed to evaluate the prognostic value of these markers in predicting recurrence risk in patients with intermediate‐risk DTC. Methods: We retrospectively analyzed consecutive patients with intermediate‐risk DTC who met the following criteria: (1) were classified as intermediate risk according to ATA guidelines; (2) showed an excellent or indeterminate response 12 months after initial treatment; and (3) had at least three consecutive years of follow‐up at our center after thyroidectomy. Nine hematological indices were calculated from blood samples collected on the day of RAI administration. Statistical analyses included ROC curve analysis, logistic regression, and Kaplan–Meier analysis. Results: A total of 282 patients were included, with a median follow‐up of 91 months. Among the indices tested, the monocyte‐to‐lymphocyte ratio (MLR) predicted recurrence better than the others. A cut‐off of 0.188 yielded 82.9% sensitivity and 54.7% specificity (AUC: 0.70). In multivariate analysis, high MLR (OR = 4.94, p < 0.001), tumor size, vascular invasion, and lymph node metastases were independently associated with recurrence. Cox regression confirmed MLR as an independent predictor of shorter recurrence‐free survival (HR = 3.01, p < 0.001). Nutritional indices showed no prognostic value. Conclusions: Pre‐RAI MLR may serve as a simple marker to refine recurrence risk stratification and personalize follow‐up in intermediate‐risk DTC.

Background: Papillary thyroid carcinoma (PTC) has an excellent prognosis, yet recurrence remains a clinical concern. Patients at intermediate risk may benefit from additional prognostic markers. We aimed to evaluate whether tumor desmoplasia predicts recurrence in intermediate-risk PTC patients and to assess its prognostic clinical utility. Methods: We conducted a retrospective study with follow-up of at least 36 months at a high-volume tertiary endocrine center. We included 121 patients with intermediate-risk PTC who achieved an excellent or indeterminate response to initial therapy at 12 months. Tumor desmoplasia was assessed on hematoxylin–eosin-stained thyroid sections by two pathologists. Desmoplasia was graded on a semi-quantitative 4-point scale based on the proportion of tumor area occupied by fibrotic stromal tissue. Patients were followed for the occurrence of biochemical or structural recurrence, which was defined as the primary study endpoint. Results: Desmoplasia was significantly associated with recurrence (odds ratio = 2.99; 95% CI: 1.51–6.34; P < 0.01). Receiver operating characteristic analysis identified grade 2 as the optimal cut-off for predicting recurrence. Notably, the negative predictive value reached 95% in patients with absent or mild desmoplasia. Kaplan–Meier analysis confirmed a significant difference in recurrence-free survival between patients with mild versus severe desmoplasia (hazard ratio = 3.00; 95% CI: 1.45–6.24; P = 0.003). Conclusion: Desmoplasia is an independent predictor of recurrence in intermediate-risk PTC. Patients with minimal or no desmoplasia have an extremely low risk of recurrence. These findings support the potential role of desmoplasia as a prognostic feature in risk stratification and personalized management of intermediate-risk PTC.

Objectives: Oncocyte-rich indeterminate thyroid nodules (O-ITNs) present diagnostic and management challenges due to overlapping features between benign and malignant lesions and differing cytological classifications. This study aimed primarily to assess the ultrasound (US) characteristics and US-based risk of O-ITNs using the American College of Radiology Thyroid Imaging Reporting And Data Systems (ACR TI-RADS). A secondary objective was to compare the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) and Italian Consensus for the Classification and Reporting of Thyroid Cytology (ICCRTC) cytological systems regarding classification and clinical management implications for O-ITNs. Methods: A retrospective study was conducted on 177 ITNs (TIR3A and TIR3B) evaluated between June 2023 and December 2024 at CTO-Alesini, Rome (Italy). Nodules were assessed with US, cytology, and histology. Oncocyte predominance was defined as >70% oncocytes on fine-needle aspiration (FNA). US features were analyzed according to ACR TI-RADS. Nodules were reclassified by BSRTC, and potential differences in clinical case management (CCM) were analyzed. Results: O-ITNs comprised 47.5% of the sample. Compared to non-O-ITNs, O-ITNs were larger and more frequently showed low-risk US features, including a higher prevalence of ACR TI-RADS 3 nodules. However, no progressive increase in the risk of malignancy (ROM) was observed across ACR TI-RADS classes within O-ITNs. Histological malignancy was identified in 47.1% of O-ITNs, a lower proportion compared to non-O-ITNs, though the difference was not statistically significant. Classification discordance with potential management impact was lower in O-ITNs (20.2%) than in non-O-ITNs (38.7%). Conclusions: O-ITNs typically exhibit benign-appearing US features and lower classification discordance between BSRTC and ICCRTC, yet US risk stratification fails to differentiate malignancy risk within O-ITNs. A tailored approach integrating cytology and cautious US interpretation is essential for optimal O-ITN management.

Background: The Mediterranean diet (MedD) exerts anti-inflammatory and anti-oxidant effects that are beneficial in autoimmune thyroid diseases (ATD). Recently, a gluten-free diet (GFD) has been proposed for non-celiac patients with Hashimoto’s thyroiditis (HT), but its usefulness is under debate. The present pilot study evaluates the effects of these two dietary regimes, with a focus on redox homeostasis, in HT. Patients and Methods: 45 euthyroid HT patients (30 F; median age 42 years) were randomly assigned to different dietary regimes: MedD (n = 15), GFD (n = 15) and free diet (FD, n = 15). Thyroid function tests, autoantibodies, and oxidative stress markers (Advanced glycation end products, AGEs; glutathione peroxidase (GPx), thioredoxin reductase (TRxR), and total plasma antioxidant activity (TEAA) were measured at baseline and after 12 weeks. Results: In the MedD group, significantly lower values of AGEs and higher values of GPX, TRX and TEAA with anti-oxidant action were detected (p < 0.05) at 12 weeks compared to baseline, and compared to the GFD and FD groups, in which the oxidative stress parameters did not change significantly (p > 0.05). No significant differences in serum levels of TSH, FT4, Ab-Tg, Ab-TPO compared to baseline were found in any group. Conclusions: This pilot study confirms the protective effect of the MedD against oxidative stress, while a GFD does not significantly influence markers of oxidative stress and/or thyroid autoimmunity/function parameters.

Macro‐thyroid‐stimulating hormone (macro‐TSH) is a complex formed by monomeric TSH with anti‐TSH antibodies, causing falsely elevated TSH levels and potential misdiagnosis of hypothyroidism. Identification of macro‐TSH is essential for proper treatment and patient follow‐up. Its diagnostic gold standard is gel filtration chromatography (GFC), which is very expensive, time‐consuming, and rarely available. Polyethylene glycol (PEG) precipitation is more accessible and inexpensive. The aim of the study was to review evidence on PEG precipitation for the detection of macro‐TSH to standardize its application in clinical practice.Methods: According to PRISMA guidelines, we conducted up to August 2024 a comprehensive search of PubMed and Scopus databases, using terms related to macro‐TSH and PEG precipitation.Results: We included 23 studies with 4476 subjects, encompassing 10 observational studies and 13 case series/reports. All studies showed a low risk of bias. They were conducted in tertiary centres and included newborns to elderly subjects. The most of evidence about the procedure has been achieved with PEG concentrations of 12.5%. The PEG‐precipitable TSH of the macro‐TSH cases was always higher than 75% ranging on average from 81% to 90%. No‐macro‐TSH cases (controls) showed a PEG‐precipitable TSH percentage ranging from 44.1% to 61.8%.Conclusions: PEG precipitation can be taken into account as a useful diagnostic tool for macro‐TSH. However, it is necessary to perform PEG precipitation in cases with a highly suspicious clinical picture and at the same time perform all available ancillary tests. PEG‐precipitable TSH > 75% can be considered a reliable diagnostic threshold for macro‐TSH cases.