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THE ROLE OF STEM CELL TRANSPLANTATION IN PATIENTS WITH R/R CLASSICAL HODGKIN LYMPHOMA TREATED WITH CHECKPOINT INHIBITORS: ITALIAN MULTICENTER EXPERIENCE
No full textThere is no agreement on the role and positioning of stem cell transplantation (SCT) in patients (pts) with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) who undertake treatment with checkpoint inhibitors (CPI). The aim of this study is to evaluate the real-world outcomes of R/R cHL pts treated with CPI, particularly the use of consolidation with autologous (autoSCT) and allogeneic SCT (alloSCT). Observational, retrospective, multicenter study which enrolled consecutive pts with R/R cHL aged 18–70 years, treated with CPI monotherapy in Italy from January 2016 to June 2023. Primary objective was the proportion of pts who received consolidation with alloSCT.
We enrolled 126 pts from 15 Italian centers. Median age at CPI start was 36 years (18–70), 54% males, 95% received first-line ABVD, 51% previously received autoSCT and 98% brentuximab vedotin. Eighty-six pts (68%) were treated with pembrolizumab, 40 (32%) with nivolumab. Overall response rate to CPI was 81%, with 49% complete responses (CRs). 107 pts (85%) were considered fit for alloSCT, of those 62 (58%) were planned to receive alloSCT. Ultimately, 41 pts (32%) received alloSCT, 36 (29%) autoSCT and 49 (39%) received no consolidation. Reasons for not performing alloSCT in candidates were progressive disease (PD) (n = 9), donor unavailability (n = 4), patient’s refusal or comorbidities (n = 4), others (n = 4). Twenty-nine out of 41 allo-transplanted pts (70%) had already received an autoSCT before CPI. Reasons for not administering a consolidation after CPI were age/comorbidity (n = 19), center’s choice (n = 9), alloSCT refusal or donor unavailability (n = 9), PD (n = 7), other (n = 5).
In pts who consolidated with alloSCT or autoSCT, median PFS and OS were not reached at a median follow-up of 27 (range 7–90) and 47.5 months (range 4–99) from CPI treatment, respectively. 48-months PFS probability were 80.6% and 81% for alloSCT and autoSCT recipients. Transplant-related mortality after alloSCT was 14.6%. In non-consolidated pts, at a median follow-up of 21 months, median PFS was 27 months. Seventeen pts (35%) were still receiving CPI at last follow-up; the main reason for interruption was PD, in 18/32 pts (56%). In pts who received SCT consolidation there was no difference in terms of PFS according to the obtainment of a CR with CPI (p = 0.93 for alloSCT and p = 0.6 for autoSCT). Instead, pts who didn’t consolidate had a significantly poorer outcome if they didn’t obtain a CR with CPI (median PFS not reached versus 11 months; p < 0.001)—Figure 1.
Outcomes after autoSCT and alloSCT consolidation are excellent, regardless of the response achieved with CPI; alloSCT was burdened by higher toxicity. Pts who achieved a CR with CPI showed good outcomes even without consolidation, however autoSCT should be considered if not performed before. Pts who do not achieve/loss the CR and have already performed autoSCT can be considered for alloSCT. Those who don’t achieve a CR and don’t consolidate have the worst outcome
The Syrian and the Anatolian: Cultural and political frontiers in the post-Hittite Eastern Mediterranean (ca. 1200-700 BCE)
Get PDFThroughout the Bronze Age, Anatolia and Syria had been deeply connected by an intense cultural and political exchange channeled by the Taurus mountains. However, after the collapse of the Hittite empire and the beginning of the Iron Age, regions on the two sides of the Taurus developed independent socio-cultural networks with limited interaction. This broad separation is generally overlooked in past research because obscured by the common cultural background that Iron Age Syro-Anatolian polities mostly inherited from the Hittite period. Warning against conceptualizations of Iron Age Syro-Anatolia as a coherent cultural complex, this paper intends to show that a “Taurus divide” affected various spheres of interaction, ranging from the cultural and linguistic landscapes to the worldviews shaping political practices of Syro-Anatolian polities. I will also argue that this divide found expression in the Assyrian “mental maps” of the area
How Action Shapes Temporal Judgments: A Study in Brain Damaged Patients Through Immersive Virtual Reality
Get PDFBackground/Objectives: Time processing is crucial for managing several aspects of our daily experiences: the continuous interaction with a changing environment requires individuals to make precise temporal judgments. Following right hemisphere damage, patients exhibited a significant alteration in perceiving temporal duration. However, this impairment usually emerges with "abstract" computerized tasks, not in everyday contexts. This study investigates estimation and reproduction of time intervals in left (LBD) and right brain damaged (RBD) patients compared to healthy controls. Methods: We adopt computerized tasks (Experiment 1) and novel virtual reality (VR) tasks where participants judged the duration of their own actions framed within a realistic VR context (Experiment 2). Results: RBD but not LBD patients underestimated time intervals, and reproduced time intervals as longer than they are. Crucially, when participants judged the temporal duration of meaningful actions performed in a realistic context through the VR scenarios, the impairment in processing time observed in RBD patients was reduced. The Voxel-lesion-symptom-mapping (VLSM) analysis revealed the neurocognitive basis of time perception. Conclusions: Our results show that meaningful actions within familiar contexts can provide a channel of information that is essential for optimal time processing, suggesting the importance of assessing time processing in an ecologically controlled manner using VR
Aging in the Skeletal Muscle Revealed by Molecular Immunohistochemical Imaging
Get PDFThe skeletal muscle is a complex organ mainly composed of multinucleated fibres responsible for contractile activity, but it also contains postnatal myogenic stem cells (i.e., satellite cells), connective cells and nervous cells. The skeletal muscle is severely affected by aging, undergoing a progressive reduction in muscle mass, strength and endurance in a condition known as sarcopenia. The mechanisms underlying sarcopenia still need to be completely clarified, but they are undoubtedly multifactorial, involving all cell types constituting the skeletal muscle. Immunohistochemistry has widely been used to investigate skeletal muscle aging, identifying age-related molecular alterations in the various myofibre components, as well as in the satellite cells and peri-fibre environment. The wide range of immunohistochemical data reported in this review is proof of the primary role played by this long-established, yet modern, technique. Its high specificity for the molecules of interest, and the possibility of imaging and quantifying the signal in the real histological or cytological sites where these molecules are located and active, makes immunohistochemistry a unique and irreplaceable tool among the laboratory techniques in biomedicine
Venetoclax therapy in chronic lymphocytic leukaemia patients relapsed after allogeneic haematopoietic stem cell transplantation
No full textAllogeneic hematopoietic stem cell transplantation (alloHSCT) remains an option for young and fit chronic lymphocytic leukaemia (CLL) patients with high-risk disease features. However, allotransplanted patients are generally excluded from clinical trials, making data regarding the use of venetoclax after alloHSCT extremely rare. We report data from 7 CLL patients who received venetoclax after alloHSCT among 53 Italian centers. These patients underwent alloHSCT between 2006 and 2021 after failing chemoimmunotherapy (7/7), ibrutinib (5/7) and/or idelalisib (1/7). Of note, 3/7 patients had already received venetoclax-based therapy before alloHSCT. Post-allo HSCT venetoclax treatment resulted safe, with adverse events not different from what reported in clinical trials. Importantly, no meaningful impact on graft versus host disease (GvHD) course was observed: 4/7 patients with pre-existing chronic GvHD had no exacerbation after venetoclax start, and only one patient developed GvHD during venetoclax therapy, that was managed as per standard clinical practice. Concerning efficacy, 5/7 patients presented a clinical response to venetoclax, with two patients achieving an undetectable minimal residual disease. To our knowledge, this is the largest reported series of CLL patients treated with venetoclax after alloHSCT. In these heavily pretreated and high-risk patients, previous alloHSCT did not compromise the feasibility of venetoclax therapy, that lacked unexpected toxicities and did not exacerbate GvHD
Rapid microwave-assisted synthesis of morphology-controlled luminescent lanthanide-doped Gd2O2S nanostructures
No full textGadolinium oxysulfide (Gd2O2S) is an attractive material of demonstrated suitability for a variety of imaging applications, leveraging its magnetic, scintillating, and luminescent properties, particularly when doped with optically active lanthanide ions (Ln3+). For many of these applications, control over size and morphology at the nanoscale is crucial. This study demonstrates the rapid microwave-assisted synthesis of colloidal Ln2O2S (Ln = Gd and dopants Yb, Er, Tb) nanostructures in as little as 20 min. Structural characterization using X-ray diffraction analysis (XRD), Raman spectroscopy, as well as transmission electron microscopy (TEM), including elemental mapping via energy dispersive X-ray spectroscopy (EDS), unveiled the key role of elemental sulphur (S8) in the reaction mixtures for materials growth. By systematically varying the Ln-to-S ratio from 1 : 0.5 to 1 : 15, controlled morphologies ranging from triangular nanoplatelets to berry- and flower-like shapes were achieved. Doping with Er3+/Yb3+ endowed the nano-triangles with upconverting and near-infrared emitting properties. Tb3+-doped Gd2O2S exhibited the characteristic green Tb3+ emission under UV excitation, while also showing X-ray excited optical luminescence (XEOL), rendering the material interesting as a potential nano-scintillator
Rhetoric and Empire: Constitutional Thought and Literature in the 19th-Century Anglosphere
No full textThe article explores the intersections between constitutional theory and literary discourse in the 19th-century Anglosphere, focusing on the interactions between Britain and the United States, in general, and on “constitutional colonialism” and the related theme of slavery, in particular. Firstly, it examines how constitutional thought was framed through rhetorical, narrative, and literary techniques, also shaping national identity and political ideology. Secondly, it assesses the UK and the U.S. constitutional frameworks through this lens, emphasising the literary and rhetorical features inherent in their constitutional contexts. The article
then investigates the tensions between constitutional promises of justice, autonomy, and citizenship, and the realities of colonial oppression, with a particular focus on slavery as one of the most divisive issues of the 19th century. As literature played a crucial role in raising public awareness and influencing political decisions regarding the theme of slavery, the article will finally highlight how some literary texts, such as Anthony Trollope’s North America, acted simultaneously as a medium of resistance and legal discourse
Green classroom effects on students' perceived restorativeness, achievement emotions, and situational distress.
No full textrestoration; emotions; learnin
Apocalittici e sfigati. Appunti sul mito (che fu) Fantozzi
No full textIl testo analizza il fenomeno Fantozzi dal punto di vista della nascita del mito popolare contemporaneo: un fenomeno di massa eppure di ricerca artistica, letteraria e cinematografica. Il testo approfondisce il ruolo dell'editor Rizzoli Sergio Pautasso, l'analogia con i "nuovi miti e nuovi riti" coniati da Gillo Dorfles, la rediviva creazione del "doppio" espressionista e la reincarnazione di eroi mitici antichi come Sisifo
Is Human Chorionic Gonadotropin a Reliable Marker for Testicular Germ Cell Tumor? New Perspectives for a More Accurate Diagnosis
Get PDFTesticular germ cell tumors (TGCTs) are the most common malignancies affecting young men between the ages of 14 and 44, accounting for about 95% of all testicular cancers. Despite being relatively rare compared to other cancers (~3.0 cases per 100,000 population, with high worldwide variability), TGCTs' incidence is increasing, particularly in industrialized countries. The initial phase of TGCT diagnosis is performed by detecting in the blood the presence of three proteins, i.e., alpha-fetoprotein (AFP), lactate dehydrogenase (LDH), and human chorionic gonadotropin (hCG). Despite these proteins being defined as markers of TGCTs, they present limitations in specificity. Indeed, AFP is not elevated in pure seminomas; LDH serum levels can be elevated in other conditions, such as liver disease or tissue damage, and hCG can be elevated in both seminomas and non-seminomas, reducing its ability to differentiate between tumor types. However, the existence of hCG variants, characterized by distinct glycosylation profiles that are differentially expressed in TGCT types and subtypes, may increase the diagnostic and prognostic potential of this hormone. Furthermore, emerging molecular biomarkers, including miRNAs and tumor cells-related epigenetic status, may offer new promising alternatives to improve diagnostic accuracy. Nonetheless, standardized diagnostic protocols still need to be implemented. Finally, understanding the biological roles of hCG isoforms and their "canonical" (e.g., LHCGR) and "non-canonical" (e.g., TGF-βR) receptor interactions may help in understanding tumor biology and therapeutic targeting