IRIS UniSR (’Università Vita-Salute San Raffaele)
Not a member yet
54666 research outputs found
Sort by
The dual nature of TDC – bridging dendritic and T cells in immunity
No full textT-DC are hematopoietic cells with unique features that provide intriguing insights into the interplay between innate and adaptive immunity. They express a combination of conventional dendritic cell (DC) and T-cell markers and are found in secondary lymphoid organs (SLOs), lungs and liver of na & iuml;ve mice, as well as in human blood. When analyzed ex vivo, T-DC can behave either as DCs or as T cells, depending on the provided stimuli. Notably, T-DC numbers and activation significantly increase in SLOs following viral infection, suggesting a potential role for T-DC in antiviral immune responses. In this review, we discuss the properties of these fascinating cells, which call for more investigation on their physiological role during immune responses to both pathogens and tumors.TDC are hematopoietic cells with unique features that provide intriguing insights into the interplay between innate and adaptive immunity. They express a combination of conventional dendritic cell (DC) and T-cell markers and are found in secondary lymphoid organs (SLOs), lungs and liver of naïve mice, as well as in human blood. When analyzed ex vivo, TDC can behave either as DCs or as T cells, depending on the provided stimuli. Notably, TDC numbers and activation significantly increase in SLOs following viral infection, suggesting a potential role for TDC in antiviral immune responses. In this review, we discuss the properties of these fascinating cells, which call for more investigation on their physiological role during immune responses to both pathogens and tumors
The “Cool Down, Then Ablate” Principle Guides the Treatment of Ventricular Tachycardias in Myocarditis
No full textThe efficacy of streptozotocin in managing pancreatic neuroendocrine neoplasms – A systematic review
No full textPancreatic neuroendocrine tumors (pan-NETs) represent a highly heterogeneous and complex pathology, with therapeutic management and prognosis influenced by several biological and clinical characteristics. Chemotherapy, including regimens based on capecitabine and temozolomide (CAPTEM) or the combination of streptozotocin and 5-fluorouracil (STZ-5FU), is indicated for rapidly growing, symptomatic, or high-burden disease requiring swift cytoreduction. Historical studies provide scientific evidence for the STZ-5FU regimen, often retrospective and frequently analyzing small series. Despite these limitations, the efficacy of this treatment is well-established, and it is included in all guidelines as a therapeutic option. This systematic review aims to gather scientific evidence on using STZ-based chemotherapy to assess its real impact in managing well-differentiated metastatic or unresectable pan-NETs
Using [18F]FDG PET/CT to Identify Optimal Responders to Neoadjuvant Therapy in Breast Cancer—Results from a Prospective Patient Cohort
Get PDFBackground/objectives: Pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer (BC) is a solid indicator of favourable prognosis, potentially also being useful for more conservative patient management. We aim to explore the potential of [18F]FDG PET/CT as a non-invasive method to predict response to NAC. Methods: In this prospective, observational cohort study, we enrolled BC patient candidates for NAC who underwent baseline and preoperative [18F]FDG PET/CT. NAC response was determined using final histopathology. PET images were assessed qualitatively and semi-quantitatively, and the findings correlated with NAC response. Results: In total, 133 BC patients were included. The visual analysis of preoperative PET/CT detected residual disease (RD) with high specificity (>93%) and moderate sensitivity, based on pCR/RD classification and RCB index. Semiquantitative measures (SUVmax, TBR) were significantly higher in non-responders across the classification methods (p < 0.001 for all). Conclusions: These findings highlight the potential of preoperative [18F]FDG PET/CT as a complementary tool for identifying excellent responders to NAC across BC subtypes or response criteria. This could inform personalised treatment and potentially allow for surgery to be omitted in selected patients
Liraglutide treatment reverses unconventional cellular defects in induced pluripotent stem cell-derived β cells harboring a partially functional WFS1 variant
No full text: Wolfram Syndrome 1 (WS1) is a rare genetic disorder caused by WFS1 variants that disrupt Wolframin, an endoplasmic reticulum-associated protein essential for cellular stress responses, Ca2+ homeostasis, and autophagy. Here, we investigated how the c.316-1G>A and c.757A>T WFS1 mutations, which yield partially functional Wolframin, affect the molecular functions of β cells and explored the therapeutic potential of the Glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide. Pancreatic β cells obtained from patient-derived induced Pluripotent Stem Cells (iPSCs) carrying this WFS1 variant exhibited reduced insulin processing and impaired secretory granule maturation, as evidenced by proinsulin accumulation and decreased prohormone convertase PC1/3. Moreover, they exhibited dysregulated Ca2+ fluxes due to altered transcription of Ca2+-related genes, including CACNA1D, and significantly reduced SNAP25 levels, leading to uncoordinated oscillations and poor glucose responsiveness. Affected cells also showed increased autophagic flux and heightened susceptibility to inflammatory cytokine-induced apoptosis. Notably, liraglutide treatment rescued these defects by normalizing Ca2+ handling, enhancing insulin processing and secretion, and reducing apoptosis, likely through modulation of the unfolded protein response. These findings underscore the importance of defining mutation-specific dysfunctions in WS1 and support targeting the GLP-1/GLP-1R axis as a therapeutic strategy
European experience of patients with HER2-positive advanced/metastatic breast cancer accessing trastuzumab deruxtecan through a named patient program: the EUROPA T-DXd study
No full textIntroduction: In January 2021, trastuzumab deruxtecan (T-DXd) received conditional approval in the European Union for the treatment of human epidermal growth factor receptor 2–positive (HER2-positive) unresectable or metastatic breast cancer in patients who had previously received two or more prior anti-HER2–based regimens. In March 2021, a named patient program (NPP) was initiated to enable eligible patients to access T-DXd when not yet locally available. This European, multicenter, multinational, observational, single-arm data collection study included heavily pretreated patients with HER2-positive metastatic breast cancer who received T-DXd under the NPP and was intended to generate real-world insights from routine clinical practice. Methods: Patients with unresectable or metastatic HER2-positive breast cancer who had received ≥2 prior anti-HER2–based regimens and were treated with T-DXd (5.4 mg/kg) under the NPP (DS8201-0002-EAP-MA) were eligible for inclusion in the study. Participation in the data collection was optional and independent of eligibility for the NPP. The primary endpoint was real-world time to treatment discontinuation. Secondary endpoints included real-world progression-free survival, prior HER2-targeted treatment patterns, reasons for T-DXd treatment discontinuation, safety, and antiemetic prophylaxis prior to T-DXd initiation. Adverse events were collected via a pharmacovigilance system. Results: In total, 256 patients (from centers across Ireland, Italy, and Spain) participated in the study. At data cutoff (March 28, 2024), 243 patients (94.9%) had discontinued treatment. The primary endpoint of median (95% confidence interval [CI]) real-world time to treatment discontinuation was 13.0 (11.2, 15.2) months. Median (95% CI) real-world progression-free survival was 15.2 (11.9, 17.3) months. The median number (range) of prior anti-HER2 lines of therapy in the metastatic setting was 3 (0–6). The main reason for T-DXd treatment discontinuation was disease progression (46.1%). Use of an antiemetic regimen with prophylactic intent was reported in 80.9% of patients. No new safety signals were identified. Conclusion: Results from this real-world study are consistent with the clinical benefit observed with T-DXd in patients with HER2-positive metastatic breast cancer in phase II/III clinical trials in the third-line setting and beyond. Clinical trial registration: https://clinicaltrials.gov/study/NCT05458401; identifier NCT0545840
Dissecting aneurysm in poor-grade subarachnoid hemorrhage
No full textObjective: Intracranial dissecting aneurysms (DAs) are rare and challenging lesions, often associated with high rates of rebleeding and poor clinical outcomes. There is limited evidence regarding optimal treatment strategies, timing, and outcomes, especially in the context of poor-grade subarachnoid hemorrhage (pSAH). The authors aimed to describe the clinical features and treatment outcomes of patients with DAs included in a national multicentric registry of pSAH and to identify independent outcome predictors within this subpopulation. Methods: The authors conducted a retrospective analysis of prospectively collected data from the multicenter Poor-Grade Aneurysmal Subarachnoid Hemorrhage (POGASH) registry, including consecutive patients admitted between January 1, 2015, and June 30, 2024. Poor grade was defined as a pretreatment World Federation of Neurosurgical Societies grade IV-V. Outcomes were assessed using the modified Rankin Scale. DAs were classified according to the Mizutani classification. Results: Of the 693 consecutive pSAH patients included in the registry, data from 60 patients with DA were analyzed. Among the 54 treated patients, 88.9% underwent endovascular treatment (vessel occlusion [48%], flow diversion [26%], and coiling [26%]), while 11.1% were treated surgically. The median (IQR) time to treatment was 6 (4-9) hours from symptom onset. Rebleeding occurred in 23.3% of patients, significantly more frequently than in the overall cohort (p < 0.048). Rebleeding independently predicted in-hospital mortality (adjusted OR 7.4; 95% CI 1.5-35.1; p = 0.011) and long-term disability (adjusted OR 0.08; 95% CI 0.007-0.98; p = 0.04). Internal carotid artery blister aneurysms were independently associated with rebleeding (adjusted OR 8; 95% CI 1.2-50; p = 0.027). Conclusions: In the context of pSAH, DAs are characterized by distinct clinicoradiological features and carry a significant risk of ultra-early rebleeding, which strongly influences clinical outcome. These findings suggest a potential benefit of ultra-early or immediate treatment in this patient population, pending further validation
Resolving the problem of surface dyslexia in Italian through inflection of irregular verbs
No full textSurface dyslexia and dysgraphia are considered diagnostic features of semantic variant primary progressive aphasia (svPPA) and are useful signs in English, a language whose attributes afford numerous opportunities to observe these phenomena. This, however, is not the case in many languages, including Italian, that have high transparency between orthography and phonology, making surface reading and spelling errors scarce. This creates a problem in applying the diagnostic recommendations for svPPA in such languages. Surface dyslexia and dysgraphia are examples of 'regularization' errors in which semantic knowledge loss leads to a failure to recognize exceptions that do not follow standard rules of pronunciation. Another form of regularization involves the incorrect inflection of irregular verbs using the rules that govern regular verbs. Unlike irregularly pronounced words, Italian, as with many languages, has numerous irregular verbs. The Italian Verb Inflection Test (IVIT) was developed to test the hypothesis that svPPA would regularize irregular verbs when inflecting them into two Italian past tenses. Results confirmed that people with svPPA made a significantly greater proportion of regularization errors compared to people with typical Alzheimer's disease or logopenic variant PPA. Without recourse to the other diagnostic features of PPA subgroups, the IVIT on its own could separate svPPA from these other two groups with 70% sensitivity and similar to 80% specificity. Regularization of irregular verb inflection offers a solution to the problem of applying the surface dyslexia/dysgraphia criterion for svPPA diagnosis in Italian
An Imaging-Based Marker to Refine Risk Stratification for Transcatheter Mitral Valve Replacement
No full textBackground: The TendyneTM transcatheter heart valve (THV) system is a promising option for high-risk patients with severe mitral regurgitation (MR) who are ineligible for surgery or transcatheter edge-to-edge repair (TEER). As most fatal complications occur within the first 90 days, this study aimed to identify anatomical predictors of in-hospital mortality after transcatheter mitral valve replacement (TMVR). Methods: In this subanalysis of the TENDER registry, data from 110 patients who underwent TMVR across 26 centers between January 2020 and June 2022 were evaluated. Preprocedural imaging parameters were analyzed, including transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), and cardiac 4D computed tomography (CT). Results: We identified LVEDDi as a significant predictor of in-hospital mortality (p = 0.022), with lower values in non-survivors (26.42 ± 3.76 mm/m2 ) than in survivors (30.37 ± 5.58 mm/m2 ). Both indexed and absolute LVEDDi predicted in-hospital complications (p < 0.001 and p = 0.008). In multivariate analysis, LVEDDi (p = 0.048; OR = 0.856) and STS score (p = 0.038; OR = 1.114) remained independent predictors of in-hospital mortality. In an extended model, only LVEDDi persisted as a significant predictor (p = 0.007), highlighting its robustness. Conclusions: This analysis identified a small LVEDDi as a novel, clinically relevant risk factor in TMVR and showed its added value alongside conventional markers. Its easy calculation supports incorporating LVEDDi thresholds into screening to improve patient selection and outcomes