IRIS UniSR (’Università Vita-Salute San Raffaele)
Not a member yet
54666 research outputs found
Sort by
Two-fold increased risk of cardiovascular events in people with MDR HIV: a matched cohort analysis with data from the PRESTIGIO registry
No full textBackground: Major adverse cardiovascular events (MACEs) may contribute to the high morbidity in people with four-class drug-resistant HIV (4DR-PWH). Objectives: To explore the probability of MACEs in 4DR-PWH compared with non-4DR controls. Methods: This was a retrospective, propensity score-matched cohort study on 4DR-PWH (cases) and non-4DR-PWH (controls), on ART, without previous MACEs. Controls were matched with cases in a 4:1 ratio for age, sex-assigned-at-birth and ART duration. Incidence rates (IRs) and incidence rate ratio (IRR) of MACEs with 95% CIs were modelled by Poisson regression. Cumulative probabilities of the first incident MACE were estimated by Kaplan-Meier curves. A multivariable stepwise Cox proportional hazards model estimated predictors of incident MACEs among covariates with univariable P < 0.100. Results: Overall, 223 4DR-PWH and 797 non-4DR-PWH were evaluated. During a median (IQR) follow-up of 8.2 (5.4-11.1) years [1833 person-years of follow-up (PY)], 23/223 (10.3%) 4DR-PWH developed 29 MACEs, IR = 1.6 (95% CI = 1.1-2.3)/100 PY. During a median follow-up of 8.4 (5.2-11.0) years (6450 PY), 42/797 (5.3%) non-4DR controls had 45 MACEs, IR = 0.7 (95% CI = 0.5-0.9)/100 PY, IRR (4DR/non-4DR) = 2.3 (95% CI = 1.4-3.6). The cumulative probabilities of the first MACE were more than doubled in 4DR-PWH (P = 0.006). At multivariable analysis, an increased risk of MACEs was associated with 4DR status [adjusted hazard ratio (aHR) = 1.9; 95% CI = 1.0-3.4], after adjusting for age, sex-assigned-at-birth, HIV load, CD4+ nadir, total cholesterol, HDL cholesterol, diabetes mellitus, statin use and baseline HCV serostatus. Conclusions: In PWH, MDR is significantly associated with a higher risk of cardiovascular events. Prompt implementation of prevention strategies is mandatory in this fragile population.Background: Major adverse cardiovascular events (MACEs) may contribute to the high morbidity in people with four-class drug-resistant HIV (4DR-PWH). Objectives: To explore the probability of MACEs in 4DR-PWH compared with non-4DR controls. Methods: This was a retrospective, propensity score-matched cohort study on 4DR-PWH (cases) and non-4DR-PWH (controls), on ART, without previous MACEs. Controls were matched with cases in a 4:1 ratio for age, sex-assigned-at-birth and ART duration. Incidence rates (IRs) and incidence rate ratio (IRR) of MACEs with 95% CIs were modelled by Poisson regression. Cumulative probabilities of the first incident MACE were estimated by Kaplan-Meier curves. A multivariable stepwise Cox proportional hazards model estimated predictors of incident MACEs among covariates with univariable P < 0.100. Results: Overall, 223 4DR-PWH and 797 non-4DR-PWH were evaluated. During a median (IQR) follow-up of 8.2 (5.4-11.1) years [1833 person-years of follow-up (PY)], 23/223 (10.3%) 4DR-PWH developed 29 MACEs, IR = 1.6 (95% CI = 1.1-2.3)/100 PY. During a median follow-up of 8.4 (5.2-11.0) years (6450 PY), 42/797 (5.3%) non-4DR controls had 45 MACEs, IR = 0.7 (95% CI = 0.5-0.9)/100 PY, IRR (4DR/non-4DR) = 2.3 (95% CI = 1.4-3.6). The cumulative probabilities of the first MACE were more than doubled in 4DR-PWH (P = 0.006). At multivariable analysis, an increased risk of MACEs was associated with 4DR status [adjusted hazard ratio (aHR) = 1.9; 95% CI = 1.0-3.4], after adjusting for age, sex-assigned-at-birth, HIV load, CD4+ nadir, total cholesterol, HDL cholesterol, diabetes mellitus, statin use and baseline HCV serostatus. Conclusions: In PWH, MDR is significantly associated with a higher risk of cardiovascular events. Prompt implementation of prevention strategies is mandatory in this fragile population
Morphometric vertebral fractures at hospitalization associate with Long COVID occurrence
No full textPurpose: Long COVID is a multisystemic syndrome leading to significant morbidity. To date, a comprehensive characterization of underlying risk factors is still being defined. Osteoporosis and vertebral fractures (VFs) were associated with worse acute COVID-19 and impaired respiratory recovery after hospitalization. Therefore, we aimed to assess the potential relationship between VFs and the occurrence of the Long COVID syndrome. Methods: Patients hospitalized for acute COVID-19 and subsequently seen in our outpatient follow-up clinic 6-months after discharge were evaluated. We retrospectively included patients with available lateral chest X-rays performed at admission suitable for VFs assessments. We excluded patients with active neoplasia, and those managed at home or those hospitalized in ICU. Long COVID was diagnosed with a multidisciplinary evaluation. Results: One-hundred sixty-two patients were included in the study. At least one VF was found in 42 patients at presentation (25.9%). Patients with VFs were significantly older and predominantly males. Long COVID was diagnosed in 25 patients (15.4%). No differences were found between patients with and without Long COVID regarding demographics and comorbidities; however, those with Long COVID were characterized by a higher prevalence of VFs at time of hospitalization for acute COVID-19 (48% vs. 22%, p = 0.01). After matching patients with and without VFs in a 1:1 ratio for demographics, comorbidities, and COVID-19 severity, a total of 84 patients were analysed and those presenting VFs were characterized by a significant higher prevalence of Long COVID (28.6% vs. 9.5%, p = 0.04) and VFs resulted as the only significant independent risk factor for Long COVID occurrence. Conclusions: We observed that prevalent VFs detected at hospital admission were distinctive clinical features of patients presenting with Long COVID 6-months after discharge, independently from acute disease severity and other confounding factors. This highlights a potential detrimental association between skeletal fragility and the development of Long COVID
Survival Outcomes of Durvalumab in Combination with Cisplatin and Gemcitabine in Advanced Biliary Tract Cancer: Real-World Results from a Single Italian Institution
No full textIntroduction: The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a retrospective analysis of its first-line treatment outcomes. Methods: We included patients with unresectable, locally advanced, or metastatic BTC treated with cisplatin, gemcitabine, plus durvalumab. The primary endpoint was overall survival (OS). Results: Thirty-three patients were enrolled. Median OS was NR and median progression free survival (PFS) was 7.6 months, after a median follow-up of 13.5 months. The investigator-assessed overall response rate was 34.5%, with stable disease in 53.0% of patients. High baseline CEA levels were associated with poor survival. Any grade adverse events (AEs) occurred in 97% of patients. Immune-related AEs (irAEs) occurred in 16% (grade >2: 6%). Presence of TP53 mutation was related to a worse OS; conversely the presence of ARID1A genomic alteration was related to a better PFS. A tendence toward a better OS was found for BRCAness patients which did not reach the statistical significance. On the other hand, BRCAness patients showed significantly higher PFS compared to no BRCAness patients. Conclusion: This real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC.Introduction: The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a retrospective analysis of its first-line treatment outcomes. Methods: We included patients with unresectable, locally advanced, or metastatic BTC treated with cisplatin, gemcitabine, plus durvalumab. The primary endpoint was overall survival (OS). Results: Thirty-three patients were enrolled. Median OS was NR and median progression free survival (PFS) was 7.6 months, after a median follow-up of 13.5 months. The investigator-assessed overall response rate was 34.5%, with stable disease in 53.0% of patients. High baseline CEA levels were associated with poor survival. Any grade adverse events (AEs) occurred in 97% of patients. Immune-related AEs (irAEs) occurred in 16% (grade >2: 6%). Presence of TP53 mutation was related to a worse OS; conversely the presence of ARID1A genomic alteration was related to a better PFS. A tendence toward a better OS was found for BRCAness patients which did not reach the statistical significance. On the other hand, BRCAness patients showed significantly higher PFS compared to no BRCAness patients. Conclusion: This real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC
Computed tomography derived predictors of left ventricular obstruction after TAVR
No full textBackground: Left ventricular obstruction (LVO) is an infrequent complication following transcatheter aortic valve replacement (TAVR) that can lead to severe hemodynamic decompensation. Previous studies have analyzed the pathophysiology of this clinical entity; however, little is known about the anatomical characteristics as assessed by computational tomography (CT) of patients at risk. Methods: Data from 349 patients were retrospectively analyzed from a single center registry of patients undergoing TAVR at San Raffaele Hospital, Milan, Italy, between January 2020 and December 2021. All patients with aortic valve stenosis and available pre-procedural CT data were included. Patients with previous heart valve surgery/interventions were excluded. Results: Post-procedurally, a total of 57 patients (16.3 %) developed LVO. They were more frequently older (83.2 vs 81.4, p = 0.04), females (67 % vs. 47 %, p < 0.05) and had smaller body surface areas and weight. CT analysis between the two groups demonstrated an acuter aorto-mitral angle (107 vs 114°, p < 0.001), shorter interventricular septum to leaflet coaptation distance (SLCL, 22.1 vs 28.1 mm, p < 0.001), smaller telo-systolic left ventricular areas (267 vs 714 mm2) and smaller LVOT area (404 vs 470 mm2, p < 0.001) in patients with LVO. Multivariate regression analysis identified as parameters able to predict the occurrence of LVO the telo-systolic LV area (OR, 0.998; 95 % CI 0.996-0.999; p = 0.001) and the anatomical distance between the interventricular septum and the point of leaflet coaptation (OR, 0.92; 95 % CI 0.86-0.99; p = 0.02). Conclusion: This is the first study identifying pre-procedural CT imaging predictors of patients at risk for LVO following TAVR. Further multicenter studies with systematic follow up will be needed to confirm these findings
Trust, Science and Disinformation
No full textIn this dissertation, my aim is to analyse the reasons and causes behind the spread of disinformation. In particular, my main interest is in what I will refer to as “scientific disinformation”, namely the kind of disinformation that regards scientific issues and topics, with a particular focus on climate change. The thesis is divided into five chapters, each with a specific purpose. The first chapter is dedicated to the definition of disinformation. I review the different definitions of disinformation available in literature and argue that it is a necessary condition, for a content to be defined as disinformative, that its creator shares it to mislead the audience. In the second chapter, I analyse the role that the digital environment, and particularly the development of social media platforms, has in the proliferation of disinformation online. I argue that the current digital environment represents a fertile soil for the proliferation of disinformation, however, the spread of the latter is not directly and entirely imputable to it. The deeper reasons and causes for the creation and spread of disinformation are indeed antecedent to the recent technological developments, and inextricably dependent on the behaviour of the users. In the third chapter, I criticise the literature on disinformation for being too anchored in an idea of the digital environment as subordinate to the offline one. I argue that, while the literature on disinformation is rightfully dedicated to verifying the hypothesis that disinformation proliferates as a result of people’s social identity protective attitudes, more research efforts should be invested on the possibility that sharing and receiving disinformation is related to people’s social identity formation processes. In the fourth chapter, I consider the possibility that the spread of scientific disinformation is caused by a diffused distrust in science. I argue that this is largely related to non-epistemic reasons, but also to epistemic ones, and I identify the particular social groups that are more likely to distrust science and share scientific disinformation. In the fifth and last chapter, I consider the possibility that the current communication between science and society presents some shortcomings that could have indirectly facilitated the formation of scientific disinformation. In the conclusive section, I review the various passages of the thesis, the positions endorsed and indicate possible future developments and lines of research.L’obiettivo di questa tesi è fornire un’analisi delle ragioni e cause della proliferazione di disinformazione. Nello specifico, mi concentrerò su un tipo particolare di disinformazione che verte su temi e questioni di natura scientifica, e che per questo chiamerò “disinformazione scientifica”, con particolare attenzione per la disinformazione sul cambiamento climatico e la scienza climatica. La tesi è composta da cinque capitoli. Il fine del primo capitolo è quello di definire in maniera chiara e precisa il concetto di disinformazione. Per farlo, presenterò le varie definizioni di disinformazione che sono state proposte in letteratura, e difenderò una posizione che ritiene sia una condizione necessaria, perché un contenuto possa dirsi disinformativo, che chi lo crea e diffonde abbia intenzione di ingannare la propria audience. Nel secondo capitolo analizzerò il ruolo dell’ambiente digitale, e in particolar modo dei social media, relativamente alla proliferazione di disinformazione. Sebbene alcune caratteristiche rendano l’ambiente digitale un contesto comunicativo all’interno del quale la proliferazione di disinformazione è facilitata, ritengo tuttavia che questo non abbia direttamente e totalmente causato questo fenomeno. Le ragioni profonde della creazione e diffusione di disinformazione sono infatti antecedenti allo sviluppo delle piattaforme digitali, e strettamente legate alla volontà, alle credenze, e al comportamento dei loro utenti. Nel terzo capitolo muovo una serie di critiche alla letteratura sulla disinformazione. In particolare, sostengo che la letteratura è ancora troppo ancorata a una visione secondo la quale l’ambiente digitale è subordinato a quello offline, e che pertanto si ritenga che online le persone si limitino a interagire sulla base delle credenze formate fuori dalla rete. Sebbene l’ipotesi che le persone condividono disinformazione a causa di una propensione a proteggere la propria identità sociale e di gruppo sia supportata dai dati, io ritengo che la ricezione e condivisione di disinformazione siano pratiche che hanno un grande impatto sulla formazione delle identità sociali, e che maggiore attenzione debba essere posta su questo aspetto. Nel quarto capitolo, considero la possibilità che la proliferazione di disinformazione scientifica sia causata da una diffusa sfiducia nei confronti della scienza e delle istituzioni scientifiche. Sostengo che questa sfiducia è soprattutto legata a questioni di natura non epistemica, ma in alcuni casi anche epistemica, e definisco i gruppi sociali che sono più inclini ad accettare e condividere disinformazione scientifica.
Nel quinto e ultimo capitolo, prendo in considerazione la possibilità che la proliferazione di disinformazione scientifica sia stata causata, indirettamente, da alcune inefficienze nella comunicazione tra scienza e società. Nelle conclusioni, mi limito a ripercorre i passaggi principali della tesi, a riassumere le posizioni difese, e a indicare possibili sviluppi di ricerca futuri
The Discrepancy Between Visual Acuity Decline and Foveal Involvement in Geographic Atrophy
No full textPurpose: To investigate the discrepancy between visual acuity (VA) decline and foveal involvement in geographic atrophy (GA) secondary to nonexudative age-related macular degeneration (AMD), and to explore how early retinal changes impact the progression of visual impairment. Design: Retrospective, longitudinal cohort study. Subjects: This study evaluated 80 eyes from 60 patients (mean age, 74.2 ± 10 years) with progressing non-neovascular AMD. Methods: Blue-light fundus autofluorescence (FAF) and spectral-domain OCT (SD-OCT) were utilized to monitor GA progression and the onset of foveal involvement. The study analyzed VA changes over an average follow-up of 60 ± 26.4 months, encompassing 785 observations. Mixed-effects models with natural splines assessed the effects of demographic and ocular characteristics on baseline VA and its rate of decline. Survival analyses compared the timing of anatomic changes with the most rapid functional declines, indicated by the highest first derivative of VA trajectories. Discrepancies between visual and anatomic changes were explored using generalized linear mixed-effects models. Main Outcome Measures: Monthly VA changes, onset and impact of foveal involvement, and factors influencing baseline VA and rate of decline. Results: Visual acuity declined consistently by an average of 0.010 logarithm of the minimum angle of resolution (LogMAR) per month (standard error [SE], 0.0003; P < 0.001). The onset of foveal involvement significantly exacerbated this decline, adding an average loss of 0.15 LogMAR (SE, 0.02; P < 0.001). Stabilization of VA typically occurred around 41 months post-foveal involvement. Significant factors associated with worse baseline VA were older age, female gender, unifocal GA morphology, and drusen-associated forms of GA (P < 0.05). The most rapid declines in VA typically occurred about 9 months (interquartile range, 0–27 months) before detectable subfoveal changes. The reticular FAF pattern (27/46 [59%] vs. 2/13 [15%], P = 0.02) and smaller baseline GA lesions (P = 0.01) were associated with faster deterioration preceding visible foveal damage. Conclusions: This study demonstrates that significant VA loss in GA can precede detectable foveal involvement, suggesting a window for early interventions to slow the progression of visual impairment. Identifying specific GA characteristics and FAF patterns as predictors of rapid VA decline supports the need for personalized treatment strategies to optimize outcomes for patients with nonexudative AMD. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article
Agamben before the Law. Biopolitics and Form-of-Life
Get PDFThis paper explores Agamben’s philosophy of law, highlighting how his view on the topic relies on his reading of sovereignty and biopolitics. Indeed, within the fertile debate on Foucault’s biopower, Agamben provides an original and radical reading of the political inclusion of life. His exegesis embeds biopolitics within a theory of the very essence of Western tradition and its fundamental elements: law and sovereignty. In the paper, deviations from a Foucauldian “orthodoxy” are traced back to the Italian philosopher’s fascination with Heidegger, Benjamin, and Kafka, where a temptation of a leakage from history emerges, as demonstrated by Agamben’s interpretation of the historical a priori. Hence, Agamben develops an unedited method and a positive political proposal. Last, this paper exhibits some shortcomings of his method, as an ontologising approach to politics could obliterate, rather than clarify, the manifold historical manifestations of power and make ineffective the positive strategies against its violence
Effects of atidarsagene autotemcel gene therapy on peripheral nerves in late-infantile metachromatic leukodystrophy
No full textThis study evaluates the efficacy of arsa-cel gene therapy (GT) in mitigating the severity and progression of peripheral neuropathy as assessed by nerve conduction velocity (NCV) in individuals affected by late-infantile metachromatic leukodystrophy (LI-MLD). This is a post-hoc analysis conducted on pre-symptomatic patients affected by LI-MLD treated with ex vivo autologous hematopoietic stem cell GT (atidarsagene autotemcel, "arsa-cel") in the context of prospective open-label, single-arm, interventional trials and expanded access programs. All patients were followed longitudinally with nerve conduction studies (NCSs) of peripheral motor (ulnar - UN, deep peroneal - DPN) and sensory (median - MN, sural - SN) nerves. These results were compared with those from a control group of untreated patients (NHx) studied with the same standardized protocol. We then analyzed the effects of baseline characteristics (age at treatment, severity of neuropathy pre-treatment expressed as age-matched NCV Z-scores) and arylsulfatase A (ARSA) enzyme activity (measured in peripheral blood myeloid CD15+ cells post treatment) on NCVs of treated patients. The primary endpoint of this post-hoc analysis was NCV, reflecting severity of demyelinating neuropathy. Changes in dermal nerve histopathology in skin biopsies were used as an exploratory outcome. Fifteen treated and 16 NHx patients were included in the analyses, with a median age (IQR) at treatment of 13 (9.1;14.5) months. At 36 months of age, treated patients showed higher estimated NCVs in all nerves compared to age-matched controls (∼15 m/s difference in motor nerves). Peripheral neuropathy was observed in the majority of treated patients at their pre-treatment examination (age range 7.3-17.4 months). Severity of pre-treatment neuropathy in treated patients did not have an effect on NCV values at 2 years post-GT, or on the rate of NCV slowing afterwards. A younger age at treatment was associated with higher NCVs of motor UN and sensory MN 2 years post-GT. Overall, ARSA levels in CD15+ cells correlated with NCVs of motor DPN at 2 years post-GT, and ARSA levels were associated with a slower decrease or a slight increase in NCVs of the DPN, UN and MN nerves afterwards. In summary, peripheral neuropathy assessed by NCV is significantly ameliorated in LI patients treated with arsa-cel compared to untreated patients of similar age. In addition to the potential role of early age at treatment in the preservation of myelin, supraphysiological ARSA levels may slow demyelination of the DPN and other peripheral nerves. Arsa-cel may exert a stronger effect on NCV than allogeneic hematopoietic stem cell transplantation due to its greater ARSA expression