IRIS UniSR (’Università Vita-Salute San Raffaele)
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Multi-stage intermediate fusion for multimodal learning to classify non-small cell lung cancer subtypes from CT and PET
No full textAccurate classification of histological subtypes of non-small cell lung cancer (NSCLC) is essential in the era of precision medicine, yet current invasive techniques are not always feasible and may lead to clinical complications. This study presents MINT, a Multi-stage INTermediate fusion approach to classify NSCLC subtypes from CT and PET images. Our method integrates the two modalities at different stages of feature extraction, using voxel-wise fusion to exploit complementary information across varying abstraction levels while preserving spatial correlations. We compare our method against unimodal approaches using only CT or PET images to demonstrate the benefits of modality fusion, and further benchmark it against early and late fusion techniques to highlight the advantages of intermediate fusion during feature extraction. Additionally, we compare our model with the only existing intermediate fusion method for histological subtype classification using PET/CT images. Our results demonstrate that the proposed method outperforms all alternatives across key metrics, with an accuracy and AUC equal to 0.724 and 0.681, respectively. This non-invasive approach has the potential to significantly improve diagnostic accuracy, facilitate more informed treatment decisions, and advance personalized care in lung cancer management
Sequele neurocognitive e neuropsichiatriche a lungo termine di COVID-19: tecnologie avanzate di apprendimento automatico e qualificazione per migliorare il benessere e la qualità della vita.
No full textLa pandemia COVID-19 ha svelato le complesse e durature sequele neuropsichiatriche note collettivamente come Long COVID, ponendo sfide senza precedenti alla salute pubblica. Questo studio esplora le basi neurobiologiche delle sequele neuro-post-acute della COVID-19 (neuro-PASC) utilizzando tecniche di fusione di dati all'avanguardia integrate con l'apprendimento automatico. Sintetizzando i dati di neuroimaging multimodale (DTI, VBM e fMRI allo stato di riposo) con i marcatori immuno-infiammatori, abbiamo identificato firme cerebrali e immunitarie specifiche per sesso associate a disfunzioni cognitive e sintomi psichiatrici nei sopravvissuti alla COVID lunga.
I risultati principali evidenziano modelli neurobiologici distinti: sono state riscontrate interruzioni della materia bianca, cambiamenti corticali e alterazioni dell'attività allo stato di riposo in correlazione con sintomi depressivi e deficit cognitivi. Questi cambiamenti strutturali e funzionali, combinati con una persistente disregolazione immuno-infiammatoria - compresi gli squilibri delle citochine e i marcatori della disfunzione della barriera emato-encefalica - hanno rivelato percorsi di vulnerabilità neuropsichiatrica dipendenti dal sesso. In particolare, le donne hanno mostrato una marcata compromissione dell'attenzione selettiva e della coordinazione psicomotoria, in linea con un profilo immunologico e di neuroimaging unico, mentre gli uomini hanno mostrato profili diversi di disregolazione cognitiva ed emotiva.
Un intervento pilota che prevedeva una terapia di recupero cognitivo (CRT) di sei settimane ha dimostrato miglioramenti promettenti nelle prestazioni cognitive, offrendo una speranza per approcci terapeutici mirati. Questa ricerca sottolinea l'importanza di metodologie integrative e guidate dai dati per decodificare la natura multiforme delle manifestazioni neuropsichiatriche della COVID lunga e per adattare gli interventi a specifici profili demografici e biologici.
Evidenziando le differenze di genere nella fisiopatologia della neuro-PASC, questo studio fornisce spunti critici per strategie personalizzate volte a migliorare la qualità della vita e il benessere dei sopravvissuti alla COVID-19, aprendo la strada a soluzioni terapeutiche più efficaci e orientate all'equità.The COVID-19 pandemic has unveiled the complex and long-lasting neuropsychiatric sequelae collectively known as Long COVID, posing unprecedented challenges to public health. This study explores the neurobiological underpinnings of neuro-post-acute sequelae of COVID-19 (neuro-PASC) using cutting-edge data fusion techniques integrated with machine learning. By synthesizing multimodal neuroimaging data (DTI, VBM, and resting-state fMRI) with immune-inflammatory markers, we identified sex-specific brain and immune signatures associated with cognitive dysfunction and psychiatric symptoms in Long COVID survivors.
Key findings highlight distinct neurobiological patterns: white matter disruptions, cortical changes, and alterations in resting-state activity were found to correlate with depressive symptoms and cognitive deficits. These structural and functional changes, combined with persistent immune-inflammatory dysregulation—including cytokine imbalances and markers of blood-brain barrier dysfunction—revealed sex-dependent pathways of neuropsychiatric vulnerability. Notably, women exhibited pronounced impairments in selective attention and psychomotor coordination, aligning with a unique immunological and neuroimaging profile, while men displayed different patterns of cognitive and emotional dysregulation.
A pilot intervention involving a six-week cognitive remediation therapy (CRT) demonstrated promising improvements in cognitive performance, offering hope for targeted therapeutic approaches. This research underscores the importance of integrative, data-driven methodologies in decoding the multifaceted nature of Long COVID neuropsychiatric manifestations and in tailoring interventions to specific demographic and biological profiles.
By highlighting gender differences in the pathophysiology of neuro-PASC, this study provides critical insights into personalized strategies aimed at improving the quality of life and well-being of COVID-19 survivors, paving the way for more effective, equity-focused healthcare solutions
Preparedness for the Digital Transition in Healthcare: Insights from an Italian Sample of Professionals
No full textBackground: The digital transition is reshaping healthcare systems through the adoption of telemedicine and electronic health records (EHRs). While these innovations enhance efficiency and access, their implementation unfolds within overstretched organizational settings characterized by workforce shortages, bureaucratic demands, and heightened psychosocial risks. Burnout, impostor syndrome, and the quality of organizational support have thus become pivotal constructs in understanding healthcare professionals’ digital preparedness. Methods: A cross-sectional online survey was conducted among 111 professionals employed at two San Donato Group facilities in Bologna, Italy. The battery included socio-demographic and occupational data, perceptions of digitalization, and validated instruments: the Maslach Burnout Inventory (MBI), the Clance Impostor Phenomenon Scale (CIPS), and the Work Organization Assessment Questionnaire (WOAQ). Descriptive analyses were complemented by Classification and Regression Trees (CART) to identify predictors of perceived digital preparedness. Results: Most respondents (88%) acknowledged the relevance of digitalization, yet 18% felt unprepared, especially women and administrative staff. Burnout levels were high, with 51% reporting emotional exhaustion, most notably among nurses and female participants. Impostor syndrome affected 43% of the sample, with nurses exhibiting the highest prevalence. CART analysis identified emotional exhaustion, impostor syndrome, and age as principal discriminators of digital preparedness. Conclusions: Our findings highlight the role of emotional exhaustion, impostor syndrome, and age in shaping perceived digital preparedness, underscoring the need for tailored training and supportive practices to ensure a sustainable digital transition
Clinical and MRI features contributing to the clinico-radiological dissociation in a large cohort of people with multiple sclerosis
Get PDFBACKGROUND: People with Multiple Sclerosis (PwMS) often show a mismatch between disability and T2-hyperintense white matter (WM) lesion volume (LV), that in general is referred to as the clinico-radiological paradox. OBJECTIVES: This study aimed to understand how an extensive clinical, neuropsychological, and MRI analysis could better elucidate the clinico-radiological dissociation in a large cohort of PwMS. METHODS: Clinical scores, such as Expanded Disability Status Scale (EDSS), 9 Hole Peg Test (9HPT), 25-foot Walking Test (25-FWT), Paced Auditory Serial Addition Test at 3 s (PASAT3), Symbol digit Modalities Test (SDMT), demographics, and 3 T-MRI of 717 PwMS and 284 healthy subjects (HS) were downloaded from the INNI database. Considering medians of LV and EDSS scores, PwMS were divided into four groups: low LV and disability (LL/LD); high LV and low disability (HL/LD); low LV and high disability (LL/HD); high LV and disability (HL/HD). MRI measures included: volumes of gray matter (GM), WM, cerebellum, basal ganglia and thalamus, spinal cord (SC) area, and functional connectivity of resting-state networks. RESULTS: The clinico-radiological dissociation involved 36% of our sample. HL/LD showed worse SDMT scores and lower global and deep GM volumes than HS and LL/LD. LL/HD showed lower GM, thalamus, and cerebellum volumes, and SC area than HS, and lower SC area than LL/LD. CONCLUSIONS: A more extensive clinical assessment, including cognitive tests, and MRI evaluation including deep GM and SC, could better describe the real status of the disease and help clinicians in early and tailored treatment in PwMS
Exploiting GDNF as a potential target for neuroprotective therapy in neurodegenerative diseases
No full textDevelopment of a novel gene therapy-based approach to drive a localized and sustained release of the neurotrophic factor GDNF to treat two different diseases associated with neurodegeneration: Parkinson’s Disease (PD) and Temporal Lobe Epilepsy (TLE).Sviluppo di un nuovo approccio basato sulla terapia genica per promuovere il rilascio localizzato e prolungato del fattore neuroftrofico GDNF al fine di trattare due diverse malattie caratterizzate da neurodegenerazione: il Morbo di Parkinson e l’Epilessia del Lobo Temporale
Identification of hepatocyte-primed cholangiocytes in the homeostatic liver by in vivo lentiviral gene transfer to mice and non-human primates
No full textLiver regeneration is supported by hepatocytes and, in certain conditions, biliary epithelial cells (BECs). BECs are facultative liver stem cells that form organoids in culture and engraft in damaged livers. However, BEC heterogeneity in the homeostatic liver remains to be fully elucidated. Here, we exploit systemic lentiviral vector (LV) administration to achieve efficient and lifelong gene transfer to BECs in mice. We find that LV-marked BECs retain organoid formation potential and predominantly respond to liver damage; however, they are less clonogenic and display a hepatocyte-primed transcriptome compared to untransduced BECs. We thus identify a BEC subset committed to hepatocyte lineage in the absence of liver damage, characterized by a transcriptional network orchestrated by hepatocyte nuclear factor 4α. We also report in vivo targeting of such BECs in non-human primates. This work highlights intrinsic BEC heterogeneity and that in vivo LV gene transfer to the liver may persist following BEC-mediated repair of hepatic damage
Hidden Nursing Care” (HNC) negli ambulatori a gestione infermieristica: I risultati preliminari dello studio esplorativo osservazionale descrittivo multicentrico sul territorio italiano (ENLIGHT-Amb)
Get PDFIntroduction: Nursing activities in outpatient settings ensure continuity of care and improved clinical outcomes but the ways in which they are delivered to citizens and the common system of attribution are not clear. This leads to the phenomenon known as Hidden Nursing Care. Objectives: To record, describe and measure the nursing activities provided in outpatient services in Italy. Materials and methods: A cross-sectional descriptive observational study was conducted using a structured survey consisting of 30 questions administered to nursing coordinators/leads and through semi-structured web interviews with nursing managers. Results: The study involved 23 healthcare organizations across 12 Italian regions, surveying a total of 220 outpatient clinics. In 2023, 1.380.337 services were provided to 449.224 patients. Most of the clinics are located within hospital and were officially established through Corporate Resolutions or Departmental Organizational Documents (N = 57; 28,5% each). 42,3% (N = 93) of the clinics fall under medical specialties. “General Nursing Outpatient Clinic” emerged as the most represented category (N = 103; 46,8%). Venous blood sampling was the most frequently provided service (N = 471.836; 34,2%). From the 12 interviews conducted with managers from 8 different regions, it emerged that responsibility for nursing outpatient clinics is often not assigned to nursing managers, and there is no system in place for attributing the costs incurred and revenues generated. Discussion and conclusions: The collected data of this preliminary report, while representing a knowledge contribution of the Hidden Nursing Care pointed out the absence of specific standardized procedures for their delivery and allocation. The introduction of a recognized fee schedule could improve resource allocation, streamline processes, and potentially reduce waiting times.Introduzione: L’attività infermieristica ambulatoriale garantisce continuità delle cure e migliori esiti clinici ma non sono chiari i percorsi della loro erogazione ai cittadini e attribuzione dei costi. Tutto ciò dà origine al fenomeno delle “Hidden Nursing Care”. Obiettivi: Censire, descrivere e misurare le attività infermieristiche erogate nei servizi ambulatoriali in Italia. Materiali e metodi: È stato condotto uno studio osservazionale descrittivo cross-sectional attraverso un’indagine strutturata composta da 30 domande somministrate a coordinatori/referenti infermieristici e da interviste web semi-strutturate ai dirigenti infermieristici. Risultati: Lo studio ha coinvolto 23 aziende in 12 regioni italiane, censendo 220 ambulatori. Nel 2023 sono state erogate 1.380.337 prestazioni a 449.224 pazienti. Gli ambulatori hanno prevalentemente sede negli ospedali e sono stati attivati con Delibere Aziendali o Documenti Organizzativi di Dipartimento (N = 57; 28,5% ciascuno). Il 42,3% (N = 93) degli ambulatori afferisce a specialistiche mediche. L’“Ambulatorio Infermieristico Generale” risulta la categoria più rappresentata (N = 103; 46,8%). Il Prelievo di sangue venoso è la prestazione più frequente (N = 471.836; 34,2%). Dalle 12 interviste effettuate ai dirigenti di 8 diverse regioni, è emerso che la responsabilità degli ambulatori infermieristici spesso non è attribuita ai dirigenti infermieristici e non esiste un sistema di attribuzione dei costi e dei ricavi sostenuti/ottenuti. Discussione e conclusioni: I dati raccolti di questa restituzione preliminare pur rappresentando un contributo conoscitivo delle “Hidden Nursing Care”, hanno evidenziato la mancanza di specifici percorsi standardizzati per la loro erogazione e attribuzione. L’introduzione di un tariffario condiviso potrebbe migliorare l’allocazione delle risorse, ottimizzare i processi e ridurre le liste d’attesa
Beyond P Values: Novel Minimal Important Difference of the Comprehensive Complication Index (CCI®) that reflects a Meaningful Outcome for Patients Undergoing Major Abdominal Surgery
No full textObjective: To estimate the Minimal Important Difference (MID) of the Comprehensive Complication Index® (CCI®) in patients undergoing abdominal surgery. Background: The CCI® is a validated metric that quantifies cumulative surgical morbidity. While the CCI® is a sensitive endpoint to detect treatment effects, a statistically significant effect does not necessarily translate into clinical relevance. Relevant differences from the patients' perspective are best captured by the MID. Methods: Individual patient data were extracted from surgical studies reporting CCI® at 30 days and using Patient Reported Outcome Measures (PROMs) with established MIDs at baseline and 30 days. To determine the MID for the CCI® we used an anchor-based approach as recommended by methods guidelines. A PROM was selected as an anchor only if the Spearman correlation coefficient between its change in score (baseline to 30 d postoperative) and the CCI® was ≥|0.30|. We used linear regression to estimate the MID of the CCI® across different anchors, and triangulation to determine a single MID. Results: Data were extracted from three published randomized controlled trials (RCTs) and one prospective observational study (n=1583 patients) in major abdominal surgery. In colorectal surgery cohorts, two sub-scores of the Short Form-36, two sub-scores of the Multidimensional Fatigue Inventory-20, the EuroQol-5-Dimension Index Score, and the EuroQol Visual Analog Scale showed a correlation with the CCI® of ≥|0.30|. This resulted in MID estimates for the CCI® ranging from 6.1 to 22.2. In hepato-pancreato-biliary surgery, one sub-score of the Short Form-36, and two sub-scores of the PROM Information System-29 questionnaire qualified as anchors providing MID estimates ranging from 6.2 to 13.8. Conclusion: We propose a mean difference of 12 points in the CCI® between treatment groups as a relevant difference in patients undergoing abdominal surgery. This MID provides an important foundation for sample size calculations and interpretation of RCTs and large real world observational studies
Immunological profile of pregnant women with preconception immunity with or without vertical transmission of human cytomegalovirus to the fetus: a retrospective observational study
Get PDFBackground: Vertical transmission of human cytomegalovirus (CMV) to the fetus (congenital CMV infection) can occur in pregnant women with preconception immunity. Maternal immunological features associated with congenital CMV infection have been poorly investigated. We aimed to characterise the immunological features of pregnant women with preconception immunity in cases with and without vertical transmission of human CMV to the fetus. Methods: In this retrospective cohort study, we included pregnant women (aged >18 years) with preconception immunity enrolled between Sept 1, 2017, and Oct 15, 2020, in the Congenital Human Cytomegalovirus Infection in Lombardy (CHILd) study (Italy) with (congenital CMV group) and without (no-congenital CMV group) intrauterine human CMV transmission. Blood was collected at 13 weeks of gestation and at delivery. The following immune parameters were measured and compared between groups: serum neutralising titres, antibody-dependent cell cytotoxicity, human CMV-specific long-term memory T cells (interleukin [IL]-7R+ and IL-2+), and effector memory CD45RA+ (TEMRA) cells. Immune parameters were also compared with those of two groups of pregnant women with human CMV primary infection enrolled at Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) in two previous studies: primary infection group 1 for antibody response (followed up for 12 months; enrolled between Feb 23, 2011, and Sept 1, 2015,) and primary infection group 2 for T-cell response (followed up for 24 months; enrolled between July 10, 2016, and March 18, 2020). Findings: 128 women were included in this study: 56 women from the CHILd study (16 women in the congenital CMV group and 40 women in the no-congenital CMV group) and 72 pregnant women with primary infection (40 in primary infection group 1 [15 with and 25 without vertical transmission] and 32 in primary infection group 2 [11 with and 21 without vertical transmission]). Higher neutralising activity (p≤0·022) but lower antibody-dependent cell cytotoxicity (p=0·0004) was observed in the congenital CMV group versus the no-congenital CMV group. Additionally, the congenital CMV group had a lower percentage of long-term memory T cells than the no-congenital CMV group (p≤0·022). No significant difference was found for TEMRA cells between congenital CMV and no-congenital CMV groups. Immunological parameters of the congenital CMV group were similar to those observed in primary infection groups 1 and 2 within 12–24 months after infection. Interpretation: Immune women with intrauterine human CMV transmission have distinct immunological parameters (different from immune women without CMV transmission, but similar to women with primary infection) and might be those who had a primary human CMV infection within a few years earlier before maternal immunity development was completed. A vaccine able to elicit a fully developed maternal immunity to human CMV is likely to be protective for the fetus. Funding: Fondazione Regionale per la Ricerca Biomedica, and Ministero della Salute
The dual effect of cholesterol on cognitive functions in REM sleep behavior disorder: A pilot study
No full textIsolated REM sleep behavior disorder (iRBD) is widely recognized as a prodromal stage of α-synucleinopathies. However, the factors influencing its clinical progression to a neurological syndrome remain poorly understood. Cholesterol metabolism has increasingly been implicated in the pathophysiology of neurodegenerative diseases, including Parkinson's disease and Dementia with Lewy Bodies. Yet, its role in iRBD has not been previously explored. This pilot study is the first to investigate the relationship between cholesterol levels and cognitive performance in individuals with iRBD. We assessed total cholesterol levels across 77 individuals with video polysomnography-confirmed iRBD, consecutively recruited at the Sleep Disorders Center of IRCSS San Raffaele Hospital in Milan, Italy. All subjects underwent an extensive neuropsychological assessment. Cholesterol levels were positively associated with language and visuospatial long-term memory performance among cognitively unimpaired individuals. Conversely, a trend toward a negative association between cholesterol levels and verbal long-term memory was observed in cognitively impaired participants. These opposite associations suggest that cholesterol may have a differential impact on cognitive function depending on cognitive status in iRBD, highlighting its complex role in early neurodegenerative processes. Further longitudinal studies are needed to confirm these associations and evaluate cholesterol's potential as a modifiable factor in the trajectory of prodromal α-synucleinopathies