Archivio istituzionale della Ricerca - Università degli Studi di Parma
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    Negative impact of corticosteroid use on outcome in patients with advanced BTCs treated with cisplatin, gemcitabine, and durvalumab: A large real‐life worldwide population

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    In recent years, there has been increasing interest in the possible prognostic impact of concomitant medications in patients with cancer treated with immunotherapy combinations. This real-world analysis aims to evaluate the impact of concomitant medications on survival outcomes in patients with advanced biliary tract cancer (BTCs) treated with cisplatin, gemcitabine and durvalumab (CGD) therapy. The study cohort included patients with a diagnosis of advanced BTCs who were taking concomitant medications for their comorbidities before the start of CGD. The primary objectives were overall survival (OS) and progression-free survival (PFS). The initial population consisted of 666 patients, who were retrospectively collected from 41 sites in 12 countries. Data on concomitant medications were available for 493 patients. After a median follow-up of 8.8 months (95% CI: 7.8-9.8), patients who did not take steroids (prednisone >10 mg/day or equivalent) or nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, before the start of CGD, had longer OS and PFS in univariate analysis. The multivariate analysis confirmed longer OS for patients who did not take steroids. Patients who did not take steroids had an OS of 14.8 months (95% CI: 13.1-29.1) versus 5.0 months (95% CI: 2.14-11.32) of patients who took prednisone >10 mg/day or equivalent. No differences were reported in terms of overall response rate (ORR), disease control rate (DCR) (p = 1.0 and p = .16, respectively), and safety profile between the two groups. Our analysis suggests that patients who did not receive steroids before the start of GCD had longer survival and highlighted the relevance of balancing concomitant medications and chemoimmunotherapy

    liberare il tempo

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    Short-term outcomes of minimally invasive gastrectomy in population with obesity versus population without obesity: the obesity paradox

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    This study aims to compare the short-term outcomes after minimally invasive gastrectomy between obese and non-obese population. Our analysis included data of 713 patients from ten departments of surgery. They were divided in non-obese group and obese group with 617 and 96 patients respectively. Significant differences were found in terms of mortality at 90 days (obese: 0 vs non-obese: 27, p = 0.037). Intraoperative data showed no significant differences in terms of conversion (obese: 4 vs non-obese: 43, p = 0.303). About postoperative complications, significant differences between the two groups were found only in terms of surgical infection (obese: 13 vs non-obese: 38, p = 0.009). About oncological outcomes, no differences were found about retrieved lymph nodes (obese: 30.71 ± 18.44 vs non-obese: 32.93 ± 17.62, p = 0.596) and about surgical radicality (R0) (obese:94 vs non-obese:594, p = 0.415). Obesity doesn’t worsen postoperative outcomes and minimally invasive gastrectomy in obese patients is related to a lower postoperative mortality

    Differential Impact of Risk Factors for Cognitive Decline in Heterosexual and Sexual Minority Older Adults in England

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    Background/Objectives: Sexual minority older adults (SMOAs) report greater subjective cognitive decline (SCD) than heterosexual older adults (HOAs). This study aimed to compare the impact of multiple psycho-social risk factors on objective and subjective cognitive decline in HOAs and SMOAs. Methods: Two samples of self-identified HOAs and SMOAs were selected from the English Longitudinal Study of Ageing. Reliable change indices for episodic and semantic memory were created to assess cognitive decline. SCD was self-reported for memory and general cognition. Depressive symptoms, loneliness, marital status and socio-economic status were investigated as risk factors. Results: No between-group differences were found in cognitive decline. Higher depression was associated with greater SCD risk and worse semantic memory decline. The latter effect was stronger in SMOAs. The findings were largely replicated in the sensitivity analysis. Conclusions: Poor mental health may represent the strongest driver of cognitive decline in SMOAs and to a greater extent than in HOAs

    The Synthesis, Characterization, and Biological Evaluation of a Fluorenyl-Methoxycarbonyl-Containing Thioxo-Triazole-Bearing Dipeptide: Antioxidant, Antimicrobial, and BSA/DNA Binding Studies for Potential Therapeutic Applications in ROS Scavenging and Drug Transport

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    We report on the synthesis and characterization of a novel fluorenyl-methoxycarbonyl (Fmoc)-containing thioxo-triazole-bearing dipeptide 5, evaluated for potential therapeutic applications. The compound was tested for its antioxidant and antimicrobial properties, demonstrating significant effects in scavenging reactive oxygen species (ROS) and inhibiting microbial growth, particularly when combined with plant extracts from an endemic Peonia species from the Caucasus. Circular dichroism (CD) binding studies with bovine serum albumin (BSA) and calf thymus DNA revealed important interactions, suggesting the dipeptide's potential in biomedically relevant conditions that involve DNA modulation. Molecular docking and CD spectra deconvolution provided additional insights into the binding mechanisms and structural characteristics of the formed complexes with the biomolecular targets. The Fmoc group enhances the dipeptide's lipophilicity, which may facilitate its interaction with cellular membranes, supporting efficient drug delivery. A computational evaluation at the omega B97XD/aug-cc-pVDZ level of theory was carried out, confirming the experimental results and revealing a powerful potential of the peptide as an antioxidant, through FMOs, MEP analysis, and antioxidant mechanism assessments. Together, these findings suggest that this dipeptide could be valuable as an antimicrobial and antioxidant agent, with potential applications in pathologies involving oxidative stress, DNA modulation, and microbial infections

    Prefazione: Appennini Migranti. Etnografia di un paese montano

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    Sarcomatoid Differentiation in Renal Cell Carcinoma: Clinical and Pathologic Heterogeneity and Outcomes With Immune Checkpoint Inhibitors—Data From the ARON-1 Study

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    Purpose: Sarcomatoid renal cell carcinoma (sRCC) represents a kidney malignancy with a sarcomatoid component associated with poor prognosis. Immunotherapy (IO)-based combinations demonstrated promising activity in sRCC, yet real-world evidence (RWE) remains limited. We aimed to characterize the clinicopathologic features and outcomes of patients with metastatic sRCC treated with first-line immune-based combinations. Patients and methods: This retrospective analysis from the ARON-1 study included 350 patients with histologically confirmed metastatic sRCC treated with first-line IO + IO, or IO + tyrosine kinase inhibitor across 66 centers in 21 countries (2016-2024). Overall survival (OS) was analyzed using Kaplan-Meier and Cox regression methods. Correlations between 2-year OS and clinical variables were assessed using Pearson's coefficient. Results: After a median follow-up of 19.1 months, median OS was 26.9 months (95% CI, 21.6 to 43.3). OS was longer in males (43.3 v 15.3 months in females; P < .001), in whom underwent nephrectomy (32.3 v 20.7 months; P = .002), and in patients without hepatic (32.3 v 15.3 months; P < .001), without skeletal (41.0 v 20.0 months; P = .007), or without lymph node metastases (43.3 v 24.6 months; P = .037). Median OS varied by International Metastatic RCC Database Consortium (IMDC) risk group: 66.5, 29.4, and 11.7 months in favorable-, intermediate-, and poor-risk patients, respectively (P < .001). Different IO regimens showed variable outcomes by risk subgroup. Limitations include retrospective design and lack of central pathology review. Conclusion: First-line IO-based combinations provide clinically meaningful survival in sRCC, with outcomes affected by sex, metastatic sites, and IMDC risk. This RWE may support a tailored therapeutic approach on the basis of baseline prognostic factors

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    Archivio istituzionale della Ricerca - Università degli Studi di Parma
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