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State of the art biology, progression, and clinical management of monoclonal B-cell lymphocytosis (MBL): consensus report from the Intercepting Blood Cancers Workshop Committee
No full textIn March 2023 and 2024, a panel of international experts convened at the first and second Intercepting Blood Cancers (IBC) Workshops, with the aim of better appreciating the diagnostic challenges, pathophysiology, and potential therapeutic interventions for precursor malignant hematology conditions. Here, we report a summary of the proceedings from the sessions focused on monoclonal B-cell lymphocytosis (MBL)/chronic lymphocytic leukemia (CLL). We highlight four main content areas: biology of MBL, clinical implications of MBL, progression of MBL and transformation from indolent CLL to aggressive disease, and opportunities for therapeutic intervention in early CLL. We additionally outline key consensus management recommendations and research goals
“Trying to Straighten a Leaning Measurement: Corrected EROA PISA in Tricuspid Regurgitation”
No full textBECOMING NEW IN OLD AGE. BODILY EXPERIENCE AND PERSONAL FLOURISHING
No full textThis paper aims at investigating ageing as a multifaceted experience in which a redefinition of one’s habitualities of experience, which often comes with a reduction of previous possibilities and a stronger sense of one’s finitude and vulnerability, can still coexist with moments of personal flourishing. I will particularly examine the bodily dimension of ageing, analyzing how one’s body feels in old age and what valences the new experiences of one’s body have for the older person. I will then argue that, despite the fact that the older person’s body often undergoes a physical decline, one’s possible personal flourishing in old age does not exclude the bodily dimension, but can reverberate positively in it, giving room to bright new experiences of one’s embodied personal life
Contextes, modèles de rationalité et histoire de la philosophie politique médiévale. L’exemple du Defensor pacis de Marsile de Padoue
No full textBiomarkers of risk of switching to dexamethasone implant for the treatment of diabetic macular oedema in real clinical practice: a multicentric study
No full textObjective To establish the influence of different optical coherence tomography (OCT) biomarkers at baseline treatment on the potential response to anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular oedema (DME). Methods Multicentric, retrospective, case-series study in patients with DME switched to dexamethasone implant injections (DEX-i) after anti-VEGF in real clinical practice. Biomarkers analysed on OCT images at baseline included intraretinal fluid (IRF), subretinal fluid (SRF), disorganisation of retinal inner layers (DRIL), disorganisation of retinal outer layers (DROL), hyperreflective foci (HRF), hyperreflective cystoid walls (HCW), dense intraretinal cyst (DIR) and vitreomacular interface (VMI) abnormalities. DME was classified according to the European School for Advanced Studies in Ophthalmology classification. Patients who were treated with anti-VEGF injections with an adequate response were selected as the control group. Results 275 eyes were analysed in this study; 209 eyes (76.0%) switched from anti-VEGF to DEX-i were compared with 66 control eyes (24.0%). Patients who required switching were statistically older, showed worse initial BCVA and higher CRT. Logistic regression analyses showed that female gender, age, central retinal thickness, type of diabetes, SRF, HCW, DIR and VMI increase the likelihood of switching. The OR regarding the need to switch generated by the presence of two of these three factors (SRF, HCW, VMI) was 48.95. Having all three multiplies it by 4.56×1016. Conclusion If baseline OCT shows two of SRF, HCW and VMI biomarkers at baseline, the risk of failure of anti-VEGF therapy is close to 50%. In the presence at baseline of all three biomarkers, failure of anti-VEGF therapy is almost certain
The Utility of Smart Multiple Daily Injection Systems in Intensive Insulin-Treated People With Diabetes: An Italian Expert Consensus
No full textBackground: Smart systems for multiple daily injections (Smart MDI) integrate continuous glucose monitoring, connected insulin pens, smartphone apps, and cloud-based data storage to provide bolus and corrective dose suggestions, reminders/alerts, automatic tracking and sharing of insulin therapy, and glycemic data to users, caregivers, and providers. This is an expert consensus on the clinical value of Smart MDI and critical points for implementation in adults and children/adolescents with diabetes. Methods: A nominal group technique combined with the estimate-talk-estimate approach was employed to achieve consensus among panel members from the Italian Intersociety Technology and Diabetes Study Group with expertise in pediatric and adult diabetes care. Results: The expert consensus indicated that glycemic profiles can be improved by using bolus dose suggestions based on glucose values, planned meals, the insulin-to-carbohydrate ratio, correction factors, and consideration of insulin-on-board. Automatic remote sharing of patient data on glycemia and insulin therapy allows clinicians to make more appropriate and timely therapeutic recommendations based on objective data. Dose tracking, bolus reminders/alerts, and reduced hypoglycemia and associated anxiety achieved through Smart MDI may improve adherence. Conclusions: Smart MDI can reduce treatment burden while improving the daily experiences and glycemic outcomes for adults and children/adolescents with type 1 or type 2 diabetes. However, high-quality clinical data are lacking, and more evidence is needed to compare the effects of Smart MDI and other advanced insulin delivery systems on glycemic and patient-reported outcomes
Erratum: Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or Bendamustine/Rituximab in Covalent Bruton Tyrosine Kinase Inhibitor-Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321) (Journal of Clinical Oncology (2025) DOI: 10.1200/JCO-25-00166)
No full textThe article by Sharman et al entitled "Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or Bendamustine/ Rituximab in Covalent Bruton Tyrosine Kinase Inhibitor- Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321)" (Journal of Clinical Oncology 10.1200/JCO-25-00166) was published online June 06, 2025, with errors. Figure A2, Forest plot of TTNT, was duplicated for Figure A1, Forest plot of IRC-assessed PFS. This has been corrected as of July 29, 2025. We apologize for the errors
Functional connectivity in neuropsychiatric diseases
No full textNeuropsychiatric disorders arise from disruptions in cognitive, affective, and behavioral integration, along with impaired neural coordination across brain regions. Over the past decade, the study of functional connectivity (FC) has transformed our understanding of these conditions, shifting the focus from localized dysfunctions to large-scale network disruptions. This chapter explores resting-state FC (Rs-FC) as a crucial tool for investigating psychiatric disorders, including schizophrenia, major depressive disorder, bipolar disorder, obsessive-compulsive disorder (OCD), and post-traumatic stress disorder. We review key findings from functional magnetic resonance imaging, positron emission tomography, electroencephalogram, and magnetoencephalography studies, highlighting common dysconnectivity patterns in the default mode network, salience network, and executive-control network. Additionally, FC-based approaches offer valuable insights into therapeutic interventions, shedding light on the effects of pharmacological and neuromodulator treatment on brain network dynamics. The integration of multimodal neuroimaging techniques enhances our understanding of psychiatric disorder pathophysiology, paving the way for personalized and network-targeted interventions
Smaller is better? Compact vs. Conventional gamma camera for sentinel lymph node localization in patients with breast cancer
No full textPurpose: Sentinel lymph node biopsy (SLNB) has been recognized as “the gold standard” for axillary staging in early breast cancer patients with clinically negative lymph nodes, resulting in significant morbidity decrease and quality of life improvement. This study aims to validate the performance of a newly developed handheld portable gamma camera (PGC) produced by Imagensys (Italy), in detecting and locating sentinel lymph nodes (SLNs) during the preoperative and intraoperative phases in breast cancer patients compared to conventional lymphoscintigraphy. Methods: Adult female patients with histologically confirmed breast cancer, candidates for surgery and SLNB, were prospectively enrolled in this open-label, pre-marketing clinical trial. All patients underwent pre- operative assessment using both the PGC and conventional lymphoscintigraphy. The performance of the two devices was compared using the Poisson regression model for incidence rate ratios (IRRs). The intrinsic sensitivity of the devices was compared using the Wilcoxon Ranked Sign Test. The utility of PGC during intra-operative procedures was also evaluated. The manoeuvrability of the devices was evaluated using operator-satisfaction questioner. Results: Sixty-eight patients (median age 50 years, BMI 21.4) were enrolled, including two patients with bilateral breast cancer, who underwent SLNB on both axillae. The PGC demonstrated superior preoperative lymph node detection rate (IRR 8.01, 95% CI 6.11–10.50; p < 0.0001) and intrinsic device sensitivity (mean counts per second 409 ± 286 vs. 255 ± 1173 for conventional device, p = 0.0003) compared to the conventional gamma camera. Intra-operative assessment with PGC was performed in 62 patients and no additional lymph nodes were visualised. However, the conventional gamma camera demonstrated superior manoeuvrability (p < 0.0001). Conclusion: The PGC handheld gamma camera showed promising results for preoperative SLN assessment in patients with breast cancer. The limited manoeuvrability may be related to the operator’s experience leading to higher inter-operator variability. Appropriate training and frequent use of nuclear medicine and surgical equipment could overcome this limitation
Evolutionary fingerprints of epithelial-to-mesenchymal transition
No full textMesenchymal plasticity has been extensively described in advanced epithelial cancers; however, its functional role in malignant progression is controversial1, 2, 3, 4–5. The function of epithelial-to-mesenchymal transition (EMT) and cell plasticity in tumour heterogeneity and clonal evolution is poorly understood. Here we clarify the contribution of EMT to malignant progression in pancreatic cancer. We used somatic mosaic genome engineering technologies to trace and ablate malignant mesenchymal lineages along the EMT continuum. The experimental evidence clarifies the essential contribution of mesenchymal lineages to pancreatic cancer evolution. Spatial genomic analysis, single-cell transcriptomic and epigenomic profiling of EMT clarifies its contribution to the emergence of genomic instability, including events of chromothripsis. Genetic ablation of mesenchymal lineages robustly abolished these mutational processes and evolutionary patterns, as confirmed by cross-species analysis of pancreatic and other human solid tumours. Mechanistically, we identified that malignant cells with mesenchymal features display increased chromatin accessibility, particularly in the pericentromeric and centromeric regions, in turn resulting in delayed mitosis and catastrophic cell division. Thus, EMT favours the emergence of genomic-unstable, highly fit tumour cells, which strongly supports the concept of cell-state-restricted patterns of evolution, whereby cancer cell speciation is propagated to progeny within restricted functional compartments. Restraining the evolutionary routes through ablation of clones capable of mesenchymal plasticity, and extinction of the derived lineages, halts the malignant potential of one of the most aggressive forms of human cancer