IRIS UniSR (’Università Vita-Salute San Raffaele)
Not a member yet
54666 research outputs found
Sort by
Health-Related Quality of Life and Dietary Supplement Use in Physically Active People and Athletes: A Cross-Sectional Study
No full textThe use of dietary supplements is widespread among athletes and physically active individuals, yet their impact on health-related quality of life (HRQoL) remains insufficiently understood. This study investigated the associations between supplement use, physical activity patterns, and HRQoL in a heterogeneous sample of 537 adults engaged in sports at amateur, professional, or recreational levels. Participants completed an online survey assessing demographics, supplement use, physical activity habits, and quality of life using the SF-36 questionnaire. Statistical analyses included chi-square tests and independent-samples t-tests to explore relationships between supplement use, body mass index (BMI), motivational variables, and HRQoL outcomes. Results indicated that 46.7% of participants reported consuming at least one supplement or substance, with an average of 1.91 products. The primary motivations included performance enhancement (30.7%) and combined performance and aesthetic goals (12.1%). A significant association emerged between supplement use and the consistency of physical activity over time, as well as the individual's motivation for engaging in exercise. Participants who maintained stable activity levels and those driven by performance or competitive motives were more likely to use supplements. In contrast, individuals exercising primarily for physical and psychological health were less likely to report supplement use. When comparing HRQoL scores, supplement users showed significantly lower levels of impairment due to emotional issues (RE), social functioning (SF), and bodily pain (BP). Among these variables, only Bodily Pain presented a small effect size, suggesting a meaningful difference between users and non-users. These findings highlight that while supplements are commonly used in athletic contexts, their association with improved quality of life is limited, and may even reflect attempts to manage physical discomfort. Further research is needed to clarify the directionality of these relationships and inform safe and evidence-based consumption
HER2 Pathway in Biliary Tract Cancer: A Snapshot of the Current Understanding and Future Directions
No full textBiliary tract cancers (BTCs) are a wide class of malignancies with dismal prognosis. The therapeutic scenario of metastatic BTCs has profoundly changed during recent years. The combination of cisplatin-gemcitabine plus immunotherapy is currently the gold standard in the first line. The more extensive comprehension of the mechanisms at the basis of BTCs and the identification of several molecular alterations has led to the introduction of target-directed therapies in the second line and beyond that have expanded the therapeutic armamentarium alongside the standard FOLFOX regimen, and for the near future, the results of some trials with targeted therapies in first line are expected. HER2 represents a promising therapeutic target detected in BTCs, being overexpressed in approximately 15–20% of cases, with a strong predilection for gallbladder carcinoma and extrahepatic cholangiocarcinoma, although a small proportion of HER2 overexpression can be detected even in intrahepatic cholangiocarcinoma. The efficacy and safety of different HER2 inhibitors have been investigated in several studies in the second line and beyond with encouraging results. This comprehensive review is intended to provide a summary of existing evidence and future perspectives on HER2 altered BTCs.Biliary tract cancers (BTCs) are a wide class of malignancies with dismal prognosis. The therapeutic scenario of metastatic BTCs has profoundly changed during recent years. The combination of cisplatin-gemcitabine plus immunotherapy is currently the gold standard in the first line. The more extensive comprehension of the mechanisms at the basis of BTCs and the identification of several molecular alterations has led to the introduction of target-directed therapies in the second line and beyond that have expanded the therapeutic armamentarium alongside the standard FOLFOX regimen, and for the near future, the results of some trials with targeted therapies in first line are expected. HER2 represents a promising therapeutic target detected in BTCs, being overexpressed in approximately 15–20% of cases, with a strong predilection for gallbladder carcinoma and extrahepatic cholangiocarcinoma, although a small proportion of HER2 overexpression can be detected even in intrahepatic cholangiocarcinoma. The efficacy and safety of different HER2 inhibitors have been investigated in several studies in the second line and beyond with encouraging results. This comprehensive review is intended to provide a summary of existing evidence and future perspectives on HER2 altered BTCs
Gamma Knife radiosurgery for primary and recurrent glioblastoma: Systematic review and meta-analysis with target- and protocol-based stratification
No full textStereotactic radiosurgery has been explored as monotherapy or in combination with systemic agents in newly diagnosed and recurrent Glioblastoma (GBM). Data specific to Gamma Knife radiosurgery (GKSR) remains sparse, and its role is not clearly defined in guidelines. A systematic review and meta-analysis were conducted. Pubmed, Embase, and Web of Science were searched for articles reporting median progression-free survival (PFS) and overall survival (OS) times, actuarial survival, adverse events (AREs), and radionecrosis (RN) rates following salvage or adjuvant GKSR in GBM. Subgroup analyses were performed based on target delineation and treatment protocol. A total of 33 studies encompassing 1732 patients were included. In the recurrent (rGBM) cohort (n = 1082), the pooled median PFS was 5.6 months and OS 21.4 months, with an RN of 13 %. The addition of bevacizumab was associated with an extended median PFS of 7.9 months and OS of 25.7 months, along with a reduced rate of recurrence (9 %). Expanding the treatment field did not significantly affect PFS, OS, or RN rates. In the adjuvant setting (n = 647), GKSR achieved a median PFS of 9.4 months, OS of 18.3 months, and an RN rate of 13 %. Progression-free survival outcomes were broadly comparable to those of other salvage modalities and appeared to be further enhanced when combined with bevacizumab. While current evidence remains insufficient to support its routine use, GKSR may be considered an adjunctive component within individualized, multimodal treatment strategies, particularly when the therapeutic goal is to enhance local disease control with minimal added toxicity. PROSPERO ID: CRD420251072605
Immunoterapia oncologica indipendente dall'HLA: ottimizzazione della terapia CIK nel glioblastoma e prospettive per le cellule NK nei tumori solidi
No full textIl glioblastoma (GBM) è il tumore maligno primario cerebrale più comune e presenta una prognosi sfavorevole nonostante i trattamenti attuali. L'immunoterapia non è riuscita a migliorare la prognosi del GBM a causa della notevole capacità del tumore di sfuggire alla sorveglianza immunitaria. I meccanismi alla base di questa refrattarietà, come l'eterogeneità tumorale, la presenza di un microambiente tumorale immunosoppressivo e il limitato traffico e infiltrazione tumorale da parte delle cellule immunitarie, rappresentano sfide comuni per l'applicazione dell'immunoterapia adottiva nei tumori solidi.
In questo progetto, abbiamo valutato il potenziale di due prototipi di immunoterapia indipendente dall'antigene, le cellule killer indotte da citochine (CIK) e le cellule natural killer (NK), come opzioni terapeutiche per i tumori solidi, con un particolare focus sul GBM.
Dato il loro consolidato utilizzo in ambito clinico, abbiamo valutato la terapia con cellule CIK per ottimizzarla nei pazienti con GBM. Abbiamo dimostrato che il lisato piastrinico umano aumenta significativamente il tasso medio di espansione delle cellule CIK derivate da pazienti con GBM (p = 0,004), mentre terapie concomitanti come la temozolomide (TMZ) e il desametasone (Dex) mostrano effetti citotossici su queste cellule (TMZ 0,1 mM; p = 0,01; Dex 10 μM; p = 0,048). Abbiamo sviluppato una pipeline basata sulla letteratura per selezionare controlli esterni adeguati, gettando le basi per un nuovo trial clinico di Fase II per valutare la terapia con cellule CIK nei pazienti con GBM. Inoltre, abbiamo ottimizzato una piattaforma di co-coltura in vitro con organoidi di GBM derivati da pazienti, dimostrando che l'inibizione del rilascio di MICA/B aumenta significativamente l'attività citotossica delle cellule CIK contro le cellule staminali del glioma (p = 0,03).
Nella seconda parte dello studio, abbiamo esplorato l'uso dell'immunoterapia con cellule NK contro i tumori solidi, concentrandoci sulla validazione del checkpoint endogeno Calcium Homeostasis Modulator 2 (CALHM2) nelle cellule NK primarie umane. CALHM2 è emerso come un target convergente da uno screening CRISPR per perdita di funzione condotto in quattro modelli murini di tumori solidi, incluso il GBM. La riduzione dell'espressione di CALHM2 ha aumentato l'attività citotossica delle cellule NK contro diversi modelli tumorali, migliorando anche la degranulazione e la produzione di citochine effettrici.
Ottimizzando l'applicabilità ed esplorando il potenziale di queste due immunoterapie indipendenti dall'antigene, in questo lavoro sottolineiamo il loro ruolo nel progresso della prossima generazione di immunoterapie in neuro-oncologia.Glioblastoma (GBM) is the most common malignant primary brain tumor and has a poor prognosis despite current treatments. Immunotherapy has failed to improve the prognosis of GBM due to the tumor's robust ability to evade immunosurveillance. The mechanisms underlying this refractoriness—such as tumor heterogeneity, the presence of an immunosuppressive tumor microenvironment, and limited tumor trafficking and infiltration—represent common challenges for the application of adoptive immunotherapy in solid tumors.
In this project, we evaluated the potential of two antigen-independent immunotherapy prototypes, cytokine-induced killer (CIK) cells and natural killer (NK) cells, as therapeutic options for solid tumors, with a particular focus on GBM.
Given their established applicability in the clinical setting, CIK cell therapy was evaluated for its optimization in GBM patients. We demonstrated that human platelet lysate significantly increased the mean expansion rate of CIK cells derived from GBM patients (p = 0.004), while concomitant therapies, such as temozolomide (TMZ) and dexamethasone (Dex), exhibited cytotoxic effects on these cells (TMZ 0.1 mM; p = 0.01; Dex 10 μM; p = 0.048). Furthermore, we developed a literature-based pipeline to select suitable external controls, laying the groundwork for a new Phase II clinical trial to evaluate CIK cell therapy in GBM patients. Additionally, we optimized an in vitro co- culture platform with patient-derived GBM organoids and demonstrated that inhibiting MICA/B shedding significantly enhanced the cytotoxic activity of CIK cells against glioma stem cells (p = 0.03).
In the second part of the study, we explored the use of NK cell immunotherapy against solid tumors, focusing on the validation of the endogenous checkpoint Calcium Homeostasis Modulator 2 (CALHM2) in human primary NK cells. CALHM2 emerged as a convergent hit from a loss-of-function CRISPR screen conducted in four solid tumor mouse models, including GBM. Knocking down CALHM2 increased NK cells killing activity against various cancer models, as well as enhanced degranulation and the production of effector cytokines.
By optimizing the applicability and exploring the potential of these two antigen- independent immunotherapies, we highlight their role in advancing the next generation of immunotherapy in neuro-oncology
Ivosidenib for IDH1-Mutant Intrahepatic Cholangiocarcinoma: Insights From a Multicenter Real-World Study
No full textBackground & Aims: Cholangiocarcinoma (CCA) is a rare cancer with limited therapeutic options and a poor prognosis. While first-line combination therapies have improved outcomes, second-line treatment remains challenging. Ivosidenib, an IDH1 inhibitor, has shown promise in treating IDH1 mutant CCA, but real-world data is limited. This study aims to evaluate ivosidenib's efficacy and safety in a large cohort of patients and compare it with second-line chemotherapy. Methods: This observational, retrospective, multicenter study included patients with advanced IDH1 mutant CCA treated with ivosidenib at 11 European institutions from May 2021 to September 2024. The primary endpoint was progression-free survival (PFS); the main secondary objectives were overall survival (OS), disease control rate (DCR), overall response rate (ORR) and safety. As a pre-planned exploratory objective, mPFS and OS of second-line ivosidenib and FOLFOX/CAPOX were compared by means of inverse probability of treatment weights (IPTW)-adjusted analysis. Results: The study included 46 patients treated with Ivosidenib; 43.5% received ivosidenib as second line and 56.5% as ≥ third line. Median PFS and OS were 3.7 (95% CI, 2.2–36.5) and 11.5 months (95% CI, 9.5–36.5). DCR was 50.0%. Grade ≥ 3 adverse events occurred in 8.7% of patients. IPTW-adjusted mPFS was 6.9 months with ivosidenib and 2.1 months with FOLFOX/CAPOX (HR: 0.36, 95% CI, 0.20–0.64, p = 0.0005), while the mOS was 15.9 and 9.0 months with ivosidenib and FOLFOX/CAPOX, respectively (HR: 0.47, 95% CI, 0.23–0.96, p = 0.0405). Conclusion: This study suggests that ivosidenib is a valid option for patients affected by metastatic IDH1 mutant CCA after at least one line of standard treatment
Coronary computed tomography angiography to predict myocardial injury in patients undergoing high-risk cancer surgery
No full textBACKGROUND: Myocardial injury is one of the most common complications after surgery and is associated with increased mortality in high-risk patients. The aim of this study was to evaluate whether preoperative coronary computed tomography angiography can predict the occurrence of myocardial injury in cancer patients undergoing high-risk surgery. METHODS: Patients diagnosed with solid tumors who possessed at least two cardiovascular risk factors and were scheduled for high-risk surgeries between August 2017 and July 2021 were included. All subjects underwent preoperative coronary computed tomography angiography, and troponin levels were measured immediately after surgery and daily within the first three days after surgery. The primary outcome was the occurrence of myocardial injury within 72 hours, defined as high-sensitivity troponin T values ≥0.014 ng/mL. RESULTS: A total of 184 patients were included. The median age was 66 years (IQR: 60; 73 years). Myocardial injury occurred in 87 patients (48%). The logistic regression identified the following as myocardial injury predictors: bladder tumor (odds ratio [OR] 10.40 [95% confidence interval 95% CI] 2.51; 43.20, P=0.001), esophageal tumor (OR 7.39 [95% CI 2.27; 24.08], P=0.001), longer anesthesia time (OR 1.24 [95% CI 1.09; 1.43], P=0.002), calcium score of 401-1000 (OR 5.92 [95% CI 1.29; 27.08, P=0.022]), and calcium score >1000 (OR 4.62 [95% CI 1.18; 18.04, P=0.028]). CONCLUSIONS: In cancer patients undergoing high-risk surgery, high calcium score on coronary computed tomography angiography identified patients who developed postoperative myocardial injury. Coronary computed tomography angiography might be considered in the surgical risk stratification of this population
Phenotypic clustering analysis of patients rejected for mitral valve interventions: implications for future transcatheter technologies
No full textAims Although several treatment options are available for patients with severe mitral regurgitation (MR), a significant proportion of patients remain ineligible for any mitral valve (MV) intervention. We aimed to analyse the phenotypic characteristics of surgical high-risk patients ineligible for MV interventions using an unsupervised phenotypic clustering approach. Methods and results Between 2014 and 2022, the CHOICE-MI registry included 984 patients with MR undergoing screening for transcatheter MV replacement at 33 international sites. For this study, only patients with screening failure receiving medical therapy alone were included. Patients receiving transcatheter or surgical treatment were excluded. A cluster analysis using K-means was performed on baseline clinical, demographic, and imaging variables to identify different patient phenotypes. Among 284 patients with MR (77.4 ± 8.82 years, 56.0% female, EuroSCORE II: 6.6 ± 5.8%) considered ineligible for any MV intervention, two clinically distinct phenogroups (PGs) were identified using unsupervised hierarchical clustering of principal components: PG1, elderly women with primary MR, preserved left ventricular function, and annular calcification; and PG2, patients with secondary MR, advanced heart failure, and high prevalence of comorbidities. One-year all-cause mortality did not differ between the PGs (PG1: 21.4%, PG2: 23.4%, P = 0.89). Predictors of mortality were albumin, renal function, and extracardiac arteriopathy for PG1 and albumin, coronary artery disease, and prior myocardial infarction for PG2. Conclusion This study identified two major subgroups among patients ineligible for mitral interventions showing profound differences in clinical and anatomical profiles. Identifying these factors may drive technological evolution to address the unmet clinical need for therapeutic options in MR patients. ClinicalTrials.gov identifier NCT04688190 (CHOICE-MI Registry)
Recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin (hf-SCIg) for inflammatory myositis: a multicenter retrospective real-world observational study
No full textBackground: Subcutaneous immunoglobulin (SCIg) is a promising alternative to intravenous Ig (IVIg) for the treatment of idiopathic inflammatory myositis (IIM), thanks to its more favorable safety profile, reduced costs, and lower impact on patients’ quality of life. We assessed the short- and long-term effectiveness and safety of recombinant human hyaluronidase-facilitated SCIg (hf-SCIg) in patients with IIM treated at different referral centers in Italy. Methods: A multicenter, retrospective, real-life cohort study was conducted on consecutive adult patients diagnosed with IIM according to the EULAR/ACR criteria, treated with hf-SCIg for remission induction or maintenance. Hf-SCIg effectiveness was assessed in terms of variation in the Medical Research Council (MRC) score, serum creatine kinase (CK) values, clinical disease manifestations and daily prednisone dosage. Safety data were also collected. Results: Twenty-six patients with IIM treated with hf-SCIg for remission induction (n = 5) or maintenance (n = 21) were included in the study (18 females; median age at diagnosis of 59 (IQR 42–64) years)). In most patients, hf-SCIg was started following previous IVIg treatment (23, 89 %) and was initiated in combination with oral corticosteroids (21, 81 %) and/or traditional or biologic DMARDs. Short-term use of hf-SCIg for remission induction appeared associated with a corticosteroid-sparing effect, without worsening of MRC score. Long-term hf-SCIg treatment for up to 24 months maintained clinical stability and serum CK levels with further improvement of MRC score. Hf-SCIg was well tolerated, with mild adverse events mostly related to local site reactions. Conclusions: Hf-SCIg seems effective and safe for induce and maintain clinical remission in patients with IIM