IRIS UniSR (’Università Vita-Salute San Raffaele)
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Erratum: Author Correction: Metabolic reprogramming of naïve regulatory T cells by IL-7 and IL-15 promotes their persistence and performance upon adoptive transfer (Communications biology (2025) 8 1 DOI: 10.1038/s42003-024-07381-1.)
No full textThe relationship between gleason score and 11c-choline pet/ct positive detection rate in prostate cancer patients with biochemical failure after radical prostatectomy: biological and methodological factors
No full textBackground: Several factors predict the detection rate of 11C-choline PET/CT in prostate cancer (PCa) patients. The role of the Gleason score (GS) is disputed. Objective: To assess whether GS predicts 11C-choline PET/CT in PCa patients. Methods: 520 PCa patients with biochemical failure after radical prostatectomy were retrospectively recruited. Univariate and multivariate binary regressions analysis was used to assess the role of predictive factors. Results: Patients with GS > 7 had significantly (P < 0.05) greater number of positive 11C-choline PET/CT than both patients with GS < 7 and patients with GS = 7. 11C-choline PET/CT positive detection rate in patients with GS = 7 did not significantly differ from patients with GS < 7 (P > 0.05). The predictive effect of GS could be detected only in patients never treated with anti-androgen therapy (ADT). Patients with GS > 7 had, in comparison to both patients with GS < 7 and to patients with GS = 7, significantly (P < 0.05) higher number of pathological 11C-choline uptake sites in pelvic or retroperitoneal lymph nodes, and in the skeleton, but not in the prostatectomy bed. However, at multivariate analysis, statistical significance was preserved by age, pathological stage and biochemical failure during ADT, but not by GS. Conclusion: Only GS > 7 predicted positive 11C-choline PET/CT and this effect was limited to drug-free and drug-naïve PCa patients, and to univariate analysis. The power of GS to predict positive 11C-choline PET/CT is lower than that of other biological factors. Methodological and biological factors affecting these results are discussed
Advancing multiple sclerosis management in older adults
No full textMultiple sclerosis (MS) typically presents in early to middle adulthood, but owing to advancements in health care, many individuals with MS now live a normal lifespan, and approximately half of the people currently living with MS are >= 50 years of age. As people living with MS age, their diagnosis, treatment and disease management become more complex owing to the effects of ageing, immunosenescence and comorbidities. Furthermore, diagnosis of late-onset MS (onset above 50 years of age) often requires additional tests, such as spinal cord imaging and cerebrospinal fluid analysis, to differentiate the disease from age-associated conditions such as cerebrovascular disease. Monitoring disease progression also becomes more complicated with increasing age, as physiological age-related changes can confound MRI findings and measurements of disability and cognition. Treatment decisions in older people with MS are also challenging, as high-efficacy treatments carry increased risks with ageing and their benefits can be reduced, yet little evidence is available to guide treatment in older adults. In this Consensus statement, we present the outcomes of an International Advisory Committee on Clinical Trials (IACCT) in MS workshop on ageing and MS; we review the current status of the field and identify knowledge gaps, and provide recommendations to advance the areas of unmet need
MicroRNA-142-3p shuttling in extracellular vesicles marks regulatory T cell dysfunction in multiple sclerosis
No full textCD4+CD25hiFoxP3+ regulatory T cells (Treg cells) are key controllers of immune self-tolerance, and their suppressive function is impaired in people with relapsing-remitting multiple sclerosis (pwRR-MS). Because the mechanisms underlying this condition are still ill-defined, we investigated the role of Treg cell–derived extracellular vesicles (Treg-EVs) in Treg cell dysfunction observed in pwRR-MS. We found that Treg-EVs from healthy individuals inhibit CD4+ conventional T (Tconv) cells by shuttling miR-142-3p from the Treg cell to the Tconv cell. There, miR-142-3p down-regulated mRNAs necessary for Tconv cell growth and effector functions, such as the redox controller cystine carrier SLC7A11. However, Treg cells from pwRR-MS released EVs containing reduced amounts of miR-142-3p, resulting in impaired suppressive function. Furthermore, Treg-EV miR-142-3p inversely correlated with the disability score and gadolinium-enhancing lesions in pwRR-MS. Together, our results elucidate a molecular mechanism involving miR-142-3p shuttled by Treg-EVs in the control of immune self-tolerance and unveil its pathogenetic implications in human autoimmunity
Tracking prodromal α-synucleinopathies: novel fluid- and tissue-based biomarker approaches for iRBD phenoconversion
No full textIsolated rapid eye movement sleep (REM) behavior disorder (iRBD) represents the strongest predictor of alpha-synucleinopathies, with over 90% of patients developing Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy after a decade. As such, iRBD provides a critical window for early diagnosis and intervention. While molecular imaging techniques have been widely explored as powerful biomarkers for early disease detection, validated, more accessible tests based on biospecimens capable of reliably predicting phenoconversion remain lacking, creating a crucial gap in the clinical management of at-risk individuals. This review provides a critical overview of the latest findings in biofluid and tissue-based biomarkers in iRBD, emphasizing the most promising candidates and outlining key directions for future research and clinical applications. While cerebrospinal fluid (CSF)-based alpha-synuclein has widely proven high diagnostic and prognostic accuracy, blood, urine, stool, skin, olfactory, and oral mucosa samples offer a feasible approach for scalable, population-level screenings in prodromal alpha-synucleinopathies. The development of multimodal biomarker panels combining accessible biofluids and tissue samples may pave the way for early intervention and more effective risk stratification in future neuroprotective trials for alpha-synucleinopathies.Statement of Significance This review provides an up-to-date synthesis of the most recent and high-impact studies on biomarkers in isolated rapid eye movement sleep (REM) sleep behavior disorder (iRBD). The growing emphasis on the applicability of less invasive and more clinically accessible biofluids and peripheral tissues reflects a broader clinical shift toward noninvasive approaches capable of supporting population-level screening and targeted interventions. Currently, no validated laboratory tests exist in clinical practice to reliably predict iRBD phenoconversion to overt alpha-synucleinopathies, creating a critical gap in early stage disease management. The insights presented here will be essential for developing early diagnostic tools and refining patient stratification strategies, both of which are essential for upcoming disease-modifying trials targeting early stage alpha-synucleinopathies
Gender and Age as Preoperative Predictors of Early Disease Progression in Patients Undergoing Surgery for Pancreatic Neuroendocrine Tumors with Liver Metastases
No full textBackground: Pancreatic neuroendocrine tumor liver metastases (PanNET LMs) are traditionally classified into three types based on their distribution. Surgery is generally considered for patients with type I/II LMs, while those with type III LMs are typically regarded as unresectable; however, type III LMs encompass a wide range of clinical scenarios, some of which may allow surgical resection. Objective: The aim of this study was to identify preoperative predictors of early progression following surgery (≤6 months) in patients with PanNETs and LMs. Methods: Consecutive patients with PanNETs and LMs who underwent surgery at San Raffaele Hospital (2010-2023) were included. Results: After a median follow-up of 56 months, 18/54 patients (34%) experienced early disease progression. Female gender was identified as a protective factor (hazard ratio [HR] 0.373, p = 0.049), while age ≥ 70 years emerged as a significant risk factor (HR 2.744, p = 0.042) for early postoperative progression. When overall disease progression was considered as an outcome, female gender was confirmed as protective (HR 0.426, p = 0.010), while type III LMs significantly increased the risk of progression (HR 2.500, p = 0.012). In the subgroup of patients with type III LMs (n = 37), female gender was confirmed as the only predictor of longer progression-free survival (HR 0.332, p = 0.006). Conclusions: This study highlights the potential role of surgery for patients with resectable or potentially resectable PanNETs and LMs. For patients with type III LMs, the role of surgery remains controversial. Nevertheless, surgery may still be an option in selected cases, particularly in younger patients and females, as part of a multidisciplinary treatment strategy
Neurovisual rehabilitation of patients with geographic atrophy secondary to age-related macular degeneration with AvDesk system
No full textPurpose The aim of this study is to evaluate the efficacy of neurovisual rehabilitation using the AvDesk training system (Linari Medical, Pisa, Italy) in patients with geographic atrophy (GA) due to age-related macular degeneration (AMD) in their eye with better visual acuity. Methods This study employed a prospective, observational, single-centre case series design. All patients underwent neurovisual rehabilitation using an AvDesk device. The protocol included sessions twice a week for a duration of 3 consecutive weeks. Before and at the end of the protocol, all patients underwent a standardized ophthalmic examination. MAIA microperimeter was used to assess fixation parameters, using bivariate contour ellipse area (BCEA) at both 63% and 95% confidence intervals, and macular sensitivity (MS). Additionally, the NEI-VFQ 25 questionnaire was administered to evaluate the clinical response. Results 17 eyes from 17 patients were included in the study. The mean (SD) best-corrected visual acuity (BCVA) at baseline was 0.55 (0.28), improving to 0.39 (0.26) LogMAR (p = 0.0002), after completing the training. The mean (SD) MS did not change, ranging from 8.81 (6.08) d ss to 8.60 (5.99) d ss (p = 0.30). Following training, both BCEA 63% and 95% values exhibited a modest reduction, although these changes did not reach statistical significance (p > 0.05). Absolute scotomas remained stable (24.41 before treatment vs. 24.65 after treatment; p = 0.83). The NEI-VFQ 25 overall score improved from 55.05 to 62.18 post-treatment (p < 0.01). Conclusions The AvDesk training system is an effective tool for neurovisual rehabilitation in AMD patients with GA, yielding improvements in BCVA, fixation stability and quality of life
