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Pre-admission beta-blocker therapy and outcomes in cardiogenic shock: Insights from the Altshock-2 Registry
No full textAimsWe aimed to assess the impact of pre-admission beta-blocker (BB) therapy on the clinical characteristics, in-hospital treatment and outcomes of patients with cardiogenic shock (CS).MethodsAll patients enrolled in the multicentre prospective Altshock-2 registry since March 2020 with available data on pre-admission BB therapy were included. Clinical characteristics, in-hospital management, haemodynamic parameters and clinical outcomes were compared in patients with versus without BB therapy. The primary endpoint was in-hospital mortality.ResultsA total of 668 patients were included [median age 66 (56-74) years, male sex 76.5%]: 299 patients (44.8%) with and 369 patients (55.2%) without previous BB therapy. Patients receiving pre-admission BB therapy had more frequently heart failure-related CS (43.8% vs. 17.9%) and less frequently cardiac arrest at presentation (20.1% vs. 27.8%, P = 0.027). Levosimendan was used less frequently and dobutamine was used more frequently in patients with baseline BB therapy (P = 0.033 and P = 0.043, respectively). Differences in the early haemodynamic response to vasoactive drugs were observed between patients with and without previous BB therapy, with a significant impact of baseline BB on mean arterial pressure (MAP) response during norepinephrine infusion (P = 0.012) and with dobutamine having a reduced response in MAP and heart rate in patients receiving BBs before admission (P = 0.023 and P = 0.001, respectively). In-hospital mortality was not significantly different between the BB and no-BB groups (40% vs. 33.7%; adjusted odds ratio 1.32, 95% confidence interval 0.84-2.07, P = 0.224). Similarly, baseline BB therapy was not independently associated with 48 h mortality (12.7% vs. 14.6%; adjusted odds ratio 1.09, 95% confidence interval 0.64-1.87, P = 0.749). The lack of association between baseline BB therapy and mortality was also confirmed at inverse probability of treatment weighting-adjusted analysis.ConclusionsIn a real-world, contemporary cohort of patients with CS, previous BB therapy influenced the haemodynamic response to vasoactive drugs, but it was not associated with in-hospital mortality
The role of insulin resistance and APOE genotype on blood–brain barrier integrity in Alzheimer's disease
Get PDFINTRODUCTION: Growing evidence suggests a connection between insulin resistance and apolipoprotein E (APOE) genotype in Alzheimer's disease (AD) pathogenesis, but the mechanisms are unclear. We examined effects of insulin resistance and APOE genotype on blood–brain barrier (BBB) integrity in AD. METHODS: BBB integrity was measured in 196 biologically-confirmed non-diabetic patients with AD evaluating CSF/serum albumin ratio, kappa and lambda free light chains (FLCs). Insulin resistance was assessed using triglyceride–glucose index (TyG). The impact of TyG on BBB integrity, and its interaction with APOE genotypes, was analyzed using multivariate models. RESULTS: Sixty-four percent of patients with AD showed altered TyG, with the 21.8% classified as high TyG. TyG subgroups were associated with BBB abnormalities, with similar AD clinical and biomarkers profile. A significant interaction between TyG and APOE ε4/ε4 genotype on BBB permeability was found in multivariate analyses. DISCUSSION: Insulin resistance is a common feature in non-diabetic AD and correlates with altered BBB permeability, interacting synergistically with APOE genotype. Highlights: Insulin resistance and apolipoprotein E (APOE) genotype are well-recognized risk factors for Alzheimer's disease (AD). Insulin resistance shows high prevalence in patients with AD. Insulin resistance is related to damage in blood–brain barrier (BBB) integrity. The association between the triglyceride–glucose (TyG) index and BBB permeability varies in relation to APOE genotype; patients with the APOE ε4/ε4 displayed higher BBB permeability
Impact of Manganese on Neuronal Function: An Exploratory Multi-Omics Study on Ferroalloy Workers in Brescia, Italy
Get PDFBackground: There is growing interest in the potential role of manganese (Mn) in the development of Alzheimer’s Disease and related dementias (ADRD). Methods: In this nested pilot study of a ferroalloy worker cohort, we investigated the impact of chronic occupational Mn exposure on cognitive function through β-amyloid (Aβ) deposition and multi-omics profiling. We evaluated six male Mn-exposed workers (median age 63, exposure duration 31 years) and five historical controls (median age: 60 years), all of whom had undergone brain PET scans. Exposed individuals showed significantly higher Aβ deposition in exposed individuals (p < 0.05). The average annual cumulative respirable Mn was 329.23 ± 516.39 μg/m3 (geometric mean 118.59), and plasma Mn levels were significantly elevated in the exposed group (0.704 ± 0.2 ng/mL) compared to controls (0.397 ± 0.18 in controls). Results: LC-MS/MS-based pathway analyses revealed disruptions in olfactory signaling, mitochondrial fatty acid β-oxidation, biogenic amine synthesis, transmembrane transport, and choline metabolism. Simoa analysis showed notable alterations in ADRD-related plasma biomarkers. Protein microarray revealed significant differences (p < 0.05) in antibodies targeting neuronal and autoimmune proteins, including Aβ (25–35), GFAP, serotonin, NOVA1, and Siglec-1/CD169. Conclusion: These findings suggest Mn exposure is associated with neurodegenerative biomarker alterations and disrupted biological pathways relevant to cognitive decline
Sustainable Water Resources Management in Large River Basins under Climate Change Scenarios- A Case Study: Euphrates-Tigris River Basin
No full textIl bacino idrografico del Tigri-Eufrate è uno dei sistemi idrici più significativi del Medio Oriente, storicamente parte della Mezzaluna Fertile, una regione che ha ospitato alcune delle più antiche civiltà della storia. Tuttavia, le sfide contemporanee, in particolare i cambiamenti climatici e le trasformazioni dell’uso del suolo, hanno esercitato una forte pressione sulle risorse idriche del bacino. Questi fattori di stress ambientale aggravano le già complesse questioni legate alla sicurezza idrica regionale, alle tensioni geopolitiche e alla sostenibilità ecologica.
Per affrontare efficacemente le sfide dello sviluppo sostenibile nel bacino del Tigri-Eufrate, è fondamentale esaminare l'evoluzione storica dei principali fattori ambientali e idrologici. Tra questi rientrano i modelli di siccità, i cambiamenti dell’uso e della copertura del suolo (LULC), le tendenze dell’aridità e la sostenibilità idrologica, tutti elementi che giocano un ruolo cruciale nel determinare la scarsità d’acqua e la vulnerabilità della regione ai cambiamenti climatici. Comprendere queste dinamiche fornisce spunti essenziali sulle trasformazioni a lungo termine che hanno influenzato la disponibilità idrica e la salute degli ecosistemi all'interno del bacino.
Alla luce di queste problematiche, il principale obiettivo della nostra analisi è fornire un'analisi storica della situazione idrologica, offrendo approfondimenti sulle complessità interconnesse della siccità, delle variazioni LULC e della sostenibilità idrologica. La ricerca valuta in modo sistematico la sostenibilità idrologica del bacino attraverso l’integrazione dell’analisi dei dati meteorologici, del telerilevamento e delle tecniche di modellizzazione GIS. Lo studio copre il periodo 1975-2022, concentrandosi su eventi storici di siccità, cambiamenti nell'uso del suolo, tendenze dell'evapotraspirazione, indici di aridità e idoneità delle colture in condizioni climatiche variabili.The Tigris-Euphrates river basin is one of the most significant water systems in the Middle East, historically forming part of the Fertile Crescent, a region that once supported some of the earliest civilizations. However, contemporary challenges, particularly climate change and land use changes, have placed substantial pressure on water resources of the basin. These environmental stressors exacerbate existing complexities related to regional water security, geopolitical tensions, and ecological sustainability.
To effectively address the challenges of sustainable development in the Tigris-Euphrates river basin, it is essential to examine the historical dynamics of key environmental and hydrological factors. These include drought patterns, land use and land cover (LULC) changes, aridity trends, and hydrological sustainability, all of which play a crucial role in shaping the region’s water scarcity and vulnerability to climate change. Understanding these dynamics provides critical insights into the long-term transformations that have affected water availability and ecosystem health in the basin.
In light of these challenges, the primary objective of our analysis is to provide a historical situation analysis that offers insights into the interconnected complexities of drought, LULC changes, and hydrological sustainability. This research systematically evaluates the hydrological sustainability of the basin by integrating meteorological data analysis, remote sensing, and GIS-based modeling techniques. The study covers the period 1975–2022, with a focus on historical drought occurrences, land-use and land-cover (LULC) changes, evapotranspiration trends, aridity indices, and crop suitability under varying climatic conditions
Eredità storica e trasformazione del paesaggio urbano. Un esempio di infrastruttura montana dell'Alta Valle Camonica (1855-1858)
No full textITA: Alla fine degli anni Quaranta del XIX secolo, l’esigenza di aggiornare lo snodo viario verso l’Aprica e il Tonale investì l’Alta Valle Camonica, un’area cruciale per i collegamenti con la Svizzera e l’Austria. Il progetto avviato, almeno amministrativamente, già durante il periodo rivoluzionario e napoleonico venne ereditato da quello austriaco. Tra il 1855 e il 1858 l’ingegnere Carlo Porro, nipote del più noto Carlo Donegani, assunse l’incarico di intervenire sul tratto passante per il comune di Edolo (BS), allargandone il sedime. Grazie a nuove risultanze documentarie emerse negli archivi di Stato di Milano, Bergamo e Brescia e agli incartamenti conservati a Edolo, si intende contestualizzare e motivare l’intervento facendo emergere come, fin dalla sua progettazione, questo si rivelò una scelta mirata alla tutela del patrimonio urbano, sociale ed economico locale. Si considerano le scelte progettuali, le tecniche costruttive e i materiali adottati; viene discusso anche il tema della ripartizione economica degli oneri. ENG: The road that connects the Upper Camonica Valley to Aprica and Tonale passes, a strategic area for connections with Switzerland and Austria, was designed at the end of the 1940s. The radical redesign of the road system was first oriented, from an administrative point of view, during the revolutionary and Napoleonic period and reconsidered during Austrian period. Eng. Carlo Porro, grandson of the more famous engineer Carlo Donegani, planned the widening of the road that crosses the municipality of Edolo (1855-1858). The paper discusses the road project and construction phases referring to new documents found in the State archives of Milan, Bergamo and Brescia, and to documentation preserved in Edolo (BS). The main topics are: analysis of the design choices; construction techniques adopted, materials used and economic contribution of Treasury and Municipality
Impact of GDMT on outcomes after mitral valve edge-to-edge repair stratified by SMR proportionality
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Neuro-toxoplasmosis in haploidentical haematopoietic stem cell transplant
No full textAllogeneic haematopoietic stem cell transplant is a routine procedure for several haematological disorders though infections are the main cause of morbidity and mortality. Rare infections, such as protozoan reactivations, can be life-threatening and clinicians should be aware of these possibilities. Herein, we present a case of neuro-toxoplasmosis post haploidentical haematopoietic stem cell transplant
What is the role of intrauterine transfusion after single intrauterine death in monochorionic twin pregnancies? Evidence from a systematic review and meta-analysis
No full textObjective: To investigate the role of intrauterine transfusion (IUT) in affecting the outcome of the surviving twin showing sign of fetal anemia after a single intrauterine fetal death (IUFD) in monochorionic (MC) twin pregnancies. Methods: PubMed, Medline and Embase databases were searched (2010-2024). The inclusion criteria were studies reporting the outcome of fetuses showing signs of fetal anemia, defined as the presence of the peak systolic velocity (PSV) of the middle cerebral artery (MCA) >1.5 MoM, after single IUFD receiving compared to those not receiving IUT. The outcomes observed were preterm birth (PTB) <34 and 28 weeks of gestation, either iatrogenic or spontaneous, co-twin intra-IUFD, co-twin neonatal death (NND), anomalies at pre- or post-natal brain imaging, abnormal neurodevelopmental outcome. Risk of bias of the included studies was assessed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. The GRADE methodology was used to assess the quality of the body of retrieved evidence. Random effect meta-analyses of proportions were used to analyze the data. Results: Six studies (78 twin pregnancies complicated by single IUFD showing signs of fetal anemia) were included in the systematic review. Assessment of risk of bias of observational studies according to the ROBINS-I tool is presented. Only one study reported a non-matched comparison between anemic fetuses undergoing compared to those not undergoing IUT, so we could not calculate the summary odd ratios, and we reported the results as pooled proportions. PTB occurred in 51.25% (95% CI 35.76-66.62) of cases < 34 weeks and in 17.99% (95% CI 5.84-34.91) < 28 weeks of gestation. Co-twin IUFD and NND were reported in 8.02% (95% CI 2.30-16.78) and 15.49% (95% CI 7.89-25.05), while abnormal findings at pre-or post-natal brain imaging in 20.30% (95% CI 11.61-30.69). Abnormal neurodevelopmental outcome was reported in 5.93% (95% CI 2.50-18.30). Conclusion: There is a very low grade of evidence that IUT can affect the outcome of anemic fetuses after single IUFD in MC pregnancies. The findings how this systematic review, in view of the limitations of the included studies, highlighted the need for large multicenter studies sharing objective protocols of prenatal management and post-natal assessment of pregnancies complicated by single IUFD are needed to report whether IUT in the anemic fetus after single IUFD can prevent mortality and neuromorbidity
Application of Ultrasound Imaging in Functional Assessment of Musculoskeletal System and Non-Invasive Characterization of Peripheral Nervous Structures
No full textIntroduzione
Le tecnologie avanzate ed abilitanti trovano un’ampia applicazione in numerosi settori della sanità. All’interno dello scenario della salute, il campo della riabilitazione è sicuramente uno di quelli maggiormente influenzati dai più recenti progressi tecnologici, probabilmente anche a causa della pandemia di COVID-19, che ne ha ulteriormente velocizzato la diffusione e l’utilizzo. Teleriabilitazione, realtà estesa, riabilitazione robotica, sistemi di analisi del movimento umano e sistemi di imaging avanzato sono diventati sempre più parte integrante di una “rivoluzione” tecnologica all’interno del sistema sanitario. All’interno di questo contesto, l’imaging ecografico presenta sicuramente innumerevoli vantaggi, e vede la sua applicazione anche all’interno del percorso riabilitativo. Questa tecnologia rappresenta infatti una modalità di imaging economica, portatile, non-invasiva e di rapida esecuzione, in quanto non richiede una preparazione specifica del paziente o del soggetto da sottoporre all’esame, e consente inoltre di effettuare una valutazione in vivo dei tessuti molli, sia in condizioni statiche che dinamiche. L’imaging ecografico può essere utilizzato infatti sia a scopo diagnostico che valutativo, oppure come strumento di misurazione nella ricerca clinica, integrato anche ad altri sistemi, come ad esempio i sistemi di analisi del movimento umano, le tecnologie indossabili per il motion tracking, i dispositivi per l’elettromiografia di superficie.
Obiettivo
L’obiettivo generale di questa tesi di dottorato è stato quindi quello di integrare differenti tecnologie abilitanti all’interno di specifici percorsi di valutazione funzionale e strutturale, con particolare attenzione per il sistema muscolo-scheletrico e nervoso. Al fine di raggiungere questo obiettivo generale, sono stati identificati quattro obiettivi specifici, in particolare: 1) analizzare l’uso integrato di tecnologie nella valutazione funzionale di disordini e delle patologie muscolo-scheletriche; 2) analizzare la possibilità di utilizzo di soluzioni tecnologiche avanzate per l’analisi del movimento umano in fase di supporto alla diagnosi; 3) analizzare l’utilizzo dell’imaging ecografico nella valutazione delle problematiche muscolo-scheletriche; 4) analizzare l’utilizzo dell’imaging ecografico nella caratterizzazione non-invasiva del sistema nervoso periferico.
Seguendo la definizione di questi obiettivi, la presente tesi di dottorato include quattro paper pubblicati su riviste scientifiche internazionali e tre studi pilota, di cui due realizzati presso lo Human Performance Lab dell’Università degli Studi di Brescia, ed uno realizzato al Rehab Technologies Lab dell’Istituto Italiano di Tecnologia.
Conclusioni
I lavori inclusi in questa tesi, concentrati prevalentemente sull’utilizzo dell’imaging ecografico, evidenziano come la collaborazione interprofessionale professionisti sanitari/ingegneri porti a vantaggi per entrambi i mondi, con un interscambio di informazioni che portano ad una più veloce e precisa risposta ai quesiti clinici, grazie alla possibilità di utilizzo di supporti tecnologici sempre più avanzati. Questo si traduce in una migliore e più veloce capacità di valutazione/diagnosi e cura, a vantaggio dei pazienti.Introduction
Advanced and enabling technologies find broad application in numerous sectors of healthcare. Within the health landscape, the field of rehabilitation is certainly one of those most influenced by the latest technological advancements, likely accelerated by the COVID-19 pandemic, which further boosted its spread and usage. Telerehabilitation, extended reality, robotic rehabilitation, human movement analysis systems, and advanced imaging systems have increasingly become integral parts of a technological "revolution" in the healthcare system. Within this context, ultrasound imaging undoubtedly offers numerous advantages, with applications in rehabilitation, too. This technology represents an economical, portable, non-invasive, and rapid imaging method that does not require specific preparation of the patient or the subject under examination and allows for in vivo evaluation of soft tissues, both in static and dynamic conditions. Ultrasound imaging can be used for diagnostic and evaluative purposes or as a measurement tool in clinical research, integrated with other systems such as human movement analysis systems, wearable motion tracking technologies, and surface electromyography devices.
Objective
Therefore, this doctoral thesis aims to integrate different enabling technologies within specific functional and structural evaluation pathways, particularly concerning the musculoskeletal and nervous systems. To achieve this general goal, four specific objectives were identified, in particular: 1) to analyse the integrated use of technologies in the functional assessment of musculoskeletal disorders and pathologies; 2) to explore the potential use of advanced technological solutions for human movement analysis in diagnostic support; 3) to analyse the use of ultrasound imaging in the evaluation of musculoskeletal issues; 4) to study the use of ultrasound imaging in the non-invasive characterisation of the peripheral nervous system.
Following the definition of these objectives, this doctoral thesis includes four papers published in international scientific journals and three pilot studies, two conducted at the Human Performance Lab of the University of Brescia and one at the Rehab Technologies Lab of the Italian Institute of Technology.
Conclusions
The works included in this thesis, mainly focused on the use of ultrasound imaging, highlight how interprofessional collaboration between health professionals and engineers brings benefits to both worlds, with an exchange of information leading to a faster and more precise answer to clinical questions, thanks to the possibility of using technological supports increasingly advanced. This results in better and faster assessment/diagnosis and care capabilities for the benefit of patients