Alessandro Rizzi

Aim: To identify publications that describe RWD databases in the field of diabetes and map their key characteristics. Methods: Databases were searched (MEDLINE, SCOPUS, CINAHL from January 2018 to October 2025) to identify relevant publications describing RWD databases. Eligible studies were identified as RWD databases that contained more than 1000 adults and were followed up for one year or longer. Metadata including population, sample size, and outcomes were then extracted. Results: A total of 610 eligible RWD databases were identified from 1779 included articles. Databases were identified in 74 countries, with the majority collected in Europe ( n = 193). Only 22 databases were identified in lower‐ and‐ middle income countries (as defined by the World Bank). Demographics, prescription, diagnosis, and biochemical information were collected frequently; however, mortality and technology related variables (CGM usage) were found in fewer datasets. Very few databases were open access however 205 mentioned having the possibility for data sharing. Conclusion: We have produced an online dashboard to summarise the RWD databases available in the field of diabetes. We found many RWD databases globally that contain a range of variables related to individuals' health; however, lower‐ and middle‐income nations are underrepresented within these data.

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.

Aims: This review evaluates the mechanisms underlying red blood cell (RBC) membrane fluidity changes in diabetes mellitus (DM) and explores strategies to assess and address these alterations. Emphasis is placed on developing a comprehensive index for membrane fluidity to improve monitoring and management in diabetic patients.Materials and Methods: We reviewed current literature on RBC membrane fluidity, focussing on lipid composition, glycation, oxidative stress, and lipid transport alterations in diabetic patients. Key methodologies include lipidomics, multi‐scale probe assessment, and machine learning integration for standardized fluidity measurement.Results: Diabetic RBCs exhibit increased membrane fluidity, primarily due to oxidative stress, increased glycation, and dysregulated lipid composition. These alterations contribute to vascular complications and impair RBC functionality. Assessing membrane composition as a nutritional marker provides insights into the metabolic impacts of glycaemic management.Conclusions: There is a critical need for a unified and comprehensive membrane fluidity index in DM, which could support personalised interventions through dietary, medicinal, and lifestyle modifications. Future research should prioritise standardising measurement techniques and integrating lipidomic data with machine learning for predictive modelling, aiming to enhance clinical outcomes for diabetic patients.

In physiological conditions, red blood cells (RBCs) demonstrate remarkable deformability, allowing them to undergo considerable deformation when passing through the microcirculation. However, this deformability is compromised in Type 1 diabetes mellitus (T1DM) and related pathological conditions. This study aims to investigate the biomechanical properties of RBCs in T1DM patients, focusing on identifying significant mechanical alterations associated with microvascular complications (MCs). We conducted a case-control study involving 38 T1DM subjects recruited from the Diabetes Care Unit at Fondazione Policlinico Gemelli Hospital, comprising 22 without MCs (control group) and 16 with MCs (pathological group). Atomic Force Microscopy was employed to assess RBC biomechanical properties in a liquid environment. We observed significant RBC stiffening in individuals with MCs, particularly during large indentations that mimic microcirculatory deformations. Univariate analysis unveiled significant differences in RBC stiffness (median difference 0.0006 N/m, p = 0.012) and RBC counts (median difference −0.39 × 10¹²/L, p = 0.009) between the MC and control groups. Bivariate logistic regression further demonstrated that combining these parameters could effectively discriminate between MC and non-MC conditions, achieving an AUC of 0.82 (95% CI: 0.67–0.97). These findings reveal the potential of RBC biomechanical properties as diagnostic and monitoring tools in diabetes research. Exploring RBC mechanical alterations may lead to the development of novel biomarkers, which, in combination with clinical markers, could facilitate the early diagnosis of diabetes-related complications.

Aim: To assess the long‐term glycaemic outcomes, with additional metrics, in adults with type 1 diabetes (T1D) using the Tandem t:slim X2 with Control‐IQ technology advanced hybrid closed‐loop (AHCL) system. Methods: This was a single‐centre, retrospective study involving 56 T1D patients who transitioned to the Tandem t:slim X2 with Control‐IQ system. The primary and secondary endpoints consisted of variations in time in tight range (TiTR; 70‐140 mg/dL) and the glycaemia risk index (GRI), respectively. Additional standardized continuous glucose monitoring (CGM) metrics, mean sensor glucose, coefficient of variation, the glucose management indicator (GMI), HbA1c and insulin daily dose, were also evaluated. Variables were measured at baseline and at 15 days, 3 months, 6 months and 1 year after Tandem t:slim X2 Control‐IQ initiation. Glucose outcomes are expressed as mean (standard deviation). Results: Use of Tandem t:slim X2 with Control‐IQ over 1 year was associated with an increase in mean TiTR, from 38.11% (17.05%) to 43.10% (13.20%) ( P = .059), and with a decline in the GRI, from 41.03 (25.48) to 28.55 (16.27) ( P = .008). CGM metrics, including time in range and time above range, showed consistent improvements. Mean sensor glucose, the GMI and HbA1c decreased significantly over time. After an initial increase, insulin daily dose remained stable throughout the 12 months. Conclusions: The results highlight the sustained effectiveness of Tandem t:slim X2 with Control‐IQ in improving glycaemic outcomes over 1 year and support the use of this technology for the management of T1D.

Background The outcome prioritisation tool (OPT) is a simple tool to ascertain the health outcome priorities of people with MLTC. Use of this tool in people aged under 65 years with MLTC has not previously been investigated. This study investigated the feasibility of using the OPT in people with MLTC aged 45 years or above, in a multi-ethnic primary-care setting, to describe the health outcome priorities of people with MLTC by age, clusters of long-term conditions and demographic factors, and to investigate any differences in prioritisation in light of the COVID-19 pandemic. Methods This was a multi-centre cross-sectional study using a questionnaire for online self-completion by people aged 45 years or above with MLTC in 19 primary care settings across the East Midlands, UK. Participants were asked to complete the OPT twice, first from their current perspective and second from their recollection of their priorities prior to COVID-19. Results The questionnaire was completed by 2,454 people with MLTC. The majority of participants agreed or strongly agreed that the OPT was easy to complete, relevant to their healthcare and will be useful in communicating priorities to their doctor. Summary scores for the whole cohort of participants showed Keeping Alive and Maintaining Independence receiving the highest scores. Statistically significant differences in prioritisation by age, clusters of long-term conditions and employment status were observed, with respondents aged over 65 most likely to prioritise Maintaining independence, and respondents aged under 65 most likely to prioritise Keeping alive. There were no differences before or after COVID-19, or by ethnicity. Conclusions The OPT is feasible and acceptable for use to elicit the health outcome priorities of people with MLTC across both middle-aged and older age groups and in a UK setting. Individual factors could influence the priorities of people with MLTC and must be considered by clinicians during consultations. HIGHLIGHTS Survey data from 2,454 patients with MLTC showed that keeping alive and maintaining independence were the top first-choice priorities from the health outcome priorities tool (OPT). The health outcomes priorities differed by socio-demographics and clusters of long-term conditions. There were no differences in health outcomes priorities before and during COVID-19. OPT is easy and acceptable to implement in a health care setting in a broad patient group. Translation of the OPT into different languages is recommended to address any potential language barrier for people with MLTC completing the OPT