Pegvisomant (PEGV) is widely used, alone or with somatostatin analogs (SSA), for GH-secreting pituitary tumors poorly controlled by SSAs alone. No information is available on specific indications for or relative efficacies of PEGV?+?SSA versus PEGV monotherapy. Aim of our study was to characterize real-life clinical use of PEGV vs. PEGV?+?SSA for SSA-resistant acromegaly (patient selection, long-term outcomes, adverse event rates, doses required to achieve control). A retrospective analysis of data collected in 2005–2010 in five hospital-based endocrinology centers in Rome was performed. Sixty-two adult acromegaly patients treated ≥6 months with PEGV (Group 1, n?=?35) or PEGV?+?SSA (Group 2, n?=?27) after unsuccessful maximal-dose SSA monotherapy (≥12 months) were enroled. Groups were compared in terms of clinical/biochemical characteristics at diagnosis and before PEGV or PEGV?+?SSA was started (baseline) and end-of-follow-up outcomes (IGF-I levels, adverse event rates, final PEGV doses). Group 2 showed higher IGF-I and GH levels and sleep apnea rates, higher rates residual tumor tissue at baseline, more substantial responses to SSA monotherapy and worse outcomes (IGF-I normalization rates, final IGF-I levels). Tumor growth and hepatotoxicity events were rare in both groups. Final daily PEGV doses were similar and significantly increased with treatment duration in both groups. PEGV and PEGV?+?SSA are safe, effective solutions for managing SSA-refractory acromegaly. PEGV?+?SSA tends to be used for more aggressive disease associated with detectable tumor tissue. With both regimens, ongoing monitoring of responses is important since PEGV doses needed to maintain IGF-I control are likely to increase over time.

Continuous glucose monitoring (CGM) might be an effective tool to improve glycemic control in gestational diabetes mellitus (GDM). Few data are available about its utilization as a diagnostic tool to find potential alterations of glycemia in subjects with normal oral glucose tolerance test (OGTT). In this preliminary prospective real-life observational study, we aimed to analyze the glycemic pattern in normal and gestational diabetes mellitus (GDM) women by continuous glucose monitoring (CGM) in order to detect potential differences between the two groups and glycemic alterations despite a normal OGTT. After the screening for GDM, subjects were connected to a CGM system for seven consecutive days. The areas under the curve of the first 60 minutes after each meal and 60 minutes before breakfast were analyzed. Women with normal OGTT that during CGM showed impaired glycemic values (more than 95 fasting or more than 140 one hour after meals or more than 120 two hours after meals) performed one week of self-monitoring of blood glucose (SMBG). After OGTT, 53 women considered normal and 46 affected by GDM were included. CGM parameters did not show any differences between the two groups with impaired glycemic excursions found in both groups. After CGM period, 33 women with normal OGTT showed abnormal glycemic patterns. These 33 women then performed one week of SMBG. After evaluation of one week of SMBG, 21 required diet therapy and 12 required insulin treatment and were followed until the delivery. An increase in gestational weight gain was observed in normal women with normal OGTT but this was not significant. No significant data were found regarding neonatal outcomes in the two groups of women. In conclusion, CGM use in pregnancy might help to detect glycemic fluctuations in women with normal OGTT, improving their treatment and outcomes.

Background: Telemedicine use in chronic disease management has markedly increased during health emergencies due to COVID-19. Diabetes and technologies supporting diabetes care, including glucose monitoring devices, software analyzing glucose data, and insulin delivering systems, would facilitate remote and structured disease management. Indeed, most of the currently available technologies to store and transfer web-based data to be shared with health care providers. Objective: During the COVID-19 pandemic, we provided our patients the opportunity to manage their diabetes remotely by implementing technology. Therefore, this study aimed to evaluate the effectiveness of 2 virtual visits on glycemic control parameters among patients with type 1 diabetes (T1D) during the lockdown period. Methods: This prospective observational study included T1D patients who completed 2 virtual visits during the lockdown period. The glucose outcomes that reflected the benefits of the virtual consultation were time in range (TIR), time above range, time below range, mean daily glucose, glucose management indicator (GMI), and glycemic variability. This metric was generated using specific computer programs that automatically upload data from the devices used to monitor blood or interstitial glucose levels. If needed, we changed the ongoing treatment at the first virtual visit. Results: Among 209 eligible patients with T1D, 166 completed 2 virtual visits, 35 failed to download glucose data, and 8 declined the visit. Among the patients not included in the study, we observed a significantly lower proportion of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) users (n=7/43, 16% vs n=155/166, 93.4% and n=9/43, 21% vs n=128/166, 77.1%, respectively; P<.001) compared to patients who completed the study. TIR significantly increased from the first (62%, SD 18%) to the second (65%, SD 16%) virtual visit (P=.02); this increase was more marked among patients using the traditional meter (n=11; baseline TIR=55%, SD 17% and follow-up TIR=66%, SD 13%; P=.01) than among those using CGM, and in those with a baseline GMI of ≥7.5% (n=46; baseline TIR=45%, SD 15% and follow-up TIR=53%, SD 18%; P<.001) than in those with a GMI of <7.5% (n=120; baseline TIR=68%, SD 15% and follow-up TIR=69%, SD 15%; P=.98). The only variable independently associated with TIR was the change of ongoing therapy. The unstandardized beta coefficient (B) and 95% CI were 5 (95% CI 0.7-8.0) (P=.02). The type of glucose monitoring device and insulin delivery systems did not influence glucometric parameters. Conclusions: These findings indicate that the structured virtual visits help maintain and improve glycemic control in situations where in-person visits are not feasible.

Background: this study investigated the expression of parathyroid hormone-related protein (PTH-rP) and PTH/PTH-rP receptor PTH-R1 in placentas from women with gestational DM (GDM), and the relationship between PTH-R1 and PTH-rP expression and pregnancy characteristics. Methods: we prospectively enrolled 78 pregnant women with GDM, and immunochemistry for PTH-rP and PTH-R1 was performed on placentas. Patients were grouped according to the positivity of PTH-R1 or PTH-rP expression, and pregnancy characteristics were compared between the two groups. Results: PTH-rP and PTH-R1 expression were highest in the extravillous cytotrophoblast and in the decidua. In extravillous cytotrophoblast, PTH-rP expression was higher in women with abnormal at fasting glycemia compared to women with abnormal 60′ or 120′ glycemia (25/25, 50% vs. 6/28, 21.4%, χ2 = 6.12, p = 0.01), and PTH-R1 expression was higher in women with abnormal oral glucose tolerance test (OGTT) at fasting glycemia compared to women with abnormal 60′ or 120′ glycemia (37/50, 74% vs. 15/28, 53.6%, χ2 = 3.37, p = 0.06). In syncytiotrophoblast, PTH-rP-positive placentas were characterized by higher incidence of 1 min Apgar score < 7 (2/9, 22.2% vs. 2/69, 2.9%, χ2 = 6.11, p = 0.01) and maternal obesity (4/9, 44.4% vs. 11/69, 16.7%, χ2 = 3.81, p = 0.05). Conclusion: placental PTH-rP and PTH-R1 expression is dependent on the type of maternal hyperglycemia, and it is associated with adverse pregnancy outcomes.

Extracellular vesicles (EVs) are increasingly recognized as promising non-invasive biomarkers for cancer and other diseases, but their clinical translation remains limited by the lack of comprehensive characterization strategies. Spectroscopic approaches such as Fourier-transform infrared (FTIR) spectroscopy can provide a global biochemical fingerprint of intact EVs, but their interpretation requires advanced analytical tools. In this study, we applied an autoencoder-based framework to attenuated total reflection FTIR (ATR-FTIR) spectra of blood-derived components, including plasma, red blood cells (RBCs), RBC-ghosts, and EVs, comprising 278 samples collected from 135 patients, to obtain latent features capable of capturing biologically meaningful variability. The autoencoder compressed spectra into 12 latent features while preserving spectral information with low reconstruction error. Unsupervised UMAP projection of the latent features separated the blood components into different clusters, supporting their biological relevance. The model was then applied to EV spectra from patients with hepatocellular carcinoma (HCC) and cirrhotic controls. Four features significantly differed between the two groups, and an elastic-net regularized logistic model evaluated with a leave-one-out cross-validation framework retained a single latent feature, achieving an out-of-fold ROC AUC of 0.785 (95% CI 0.602–0.967), with performance broadly comparable to that typically reported for AFP, the most commonly used biomarker for HCC. This study provides the first proof-of-concept that an autoencoder can be applied to FTIR spectra of EVs, extracting biologically relevant latent features with potential application in cancer detection.

In this work, we will investigate if red blood cell (RBC) membrane fluidity, influenced by several hyperglycemia-induced pathways, could provide a complementary index of HbA1c to monitor the development of type 2 diabetes mellitus (T2DM)-related macroangiopathic complications such as Peripheral Artery Disease (PAD). The contextual liquid crystalline (LC) domain spatial organization in the membrane was analysed to investigate the phase dynamics of the transition. Twenty-seven patients with long-duration T2DM were recruited and classified in DM, including 12 non-PAD patients, and DM + PAD, including 15 patients in any stage of PAD. Mean values of RBC generalized polarization (GP), representative of membrane fluidity, together with spatial organization of LC domains were compared between the two groups; p-values < 0.05 were considered statistically significant. Although comparable for anthropometric characteristics, duration of diabetes, and HbA1c, RBC membranes of PAD patients were found to be significantly more fluid (GP: 0.501 ± 0.026) than non-PAD patients (GP: 0.519 ± 0.007). These alterations were shown to be triggered by changes in both LC microdomain composition and distribution. We found a decrease in Feret diameter from 0.245 ± 0.281 μm in DM to 0.183 ± 0.124 μm in DM + PAD, and an increase in circularity. Altered RBC membrane fluidity is correlated to a spatial reconfiguration of LC domains, which, by possibly altering metabolic function, are associated with the development of T2DM-related macroangiopathic complications.