Archivio istituzionale della ricerca - Università dell'Insubria
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An integrated perspective on the interactions between Quercus cerris fine roots and microbial community in top- and sub-layers of urban rhizosphere
The rhizosphere in urban environments is crucial to plant health and ecosystem sustainability. However, little is known about the spatial variability of the rhizosphere in urban forest ecosystems, especially for holobionts based on large organisms like trees. Thus, we aimed to identify the variations of the fine root functional traits of Quercus cerris and of the microbial community composition and their reciprocal dependencies analyzing the rhizosphere of the top- and sub-layer soil of non-urban, peri-urban and urban sites. Our findings showed that in non-urban forests, fine roots are mostly shallow and interact with diverse microbial phyla in the topsoil influencing necromass and, thus, carbon cycling. In peri-urban forests, fine root traits vary by depth, leading to higher specific root length in the top-layer and contributing to possible microhabitat fragmentation. In urban areas, more interactions occur at greater depths, mainly influencing root length and biomass, though without significant changes possibly indicating environmental disturbance. Although it is impossible to dissect every single interaction between roots and microbial phyla, underrepresented microbial phyla were demonstrated to play significant roles in shaping the root-microbiome interplay. These preliminary observations need further investigation to provide more insights into the reciprocal interplay spatially occurring in the rhizosphere
Hysterectomy or not for borderline ovarian tumor in menopause?
Background: The role of hysterectomy for borderline ovarian tumor (BOT) among postmenopausal women is still unclear. Objective(s): To assess the impact of hysterectomy on survival outcomes in postmenopausal women with BOT. Study design: This study was a national, multicenter, observational, retrospective, cohort study including all consecutive eligible postmenopausal patients who underwent primary surgery for BOT in 20 Italian centers from January 2005 to December 2017. Patients were divided into two groups: hysterectomy group vs no-hysterectomy group. Primary outcome was disease-free survival (DFS) at 5 years of follow-up; secondary outcomes were overall survival (OS) and disease-specific survival (DSS) at 5 years of follow-up, hazard ratio (HR) for recurrence, death of any cause and death due to BOT, peri-operative complications rates. Results: 483 patients were included, 144 (29.8 %) women in the no-hysterectomy group and 339 (70.2 %) in the hysterectomy group. Recurrences were significantly more common in the no-hysterectomy group compared to hysterectomy one (8.3 % vs 2.7 %; p = 0.012). The 5-year DFS rate was lower in the no-hysterectomy group than that in the hysterectomy one [92.4 % vs 98.5 %; p = 0.007]. At univariate analyses, women who underwent hysterectomy showed HR of 0.312 (95 %CI:0.131–0.740; p = 0.008) for recurrence. At multivariate analysis, hysterectomy was found to be an independent protective factor for recurrence (HR: 0.253, 95 %CI:0.103–0.618, p < 0.003). Conclusions: In postmenopausal women with BOT, hysterectomy is associated with a decreased risk of recurrence, while it does not affect the risk of death from any cause or death due to the disease. Based on these findings, hysterectomy should be routinely integrated into the surgical staging of BOT in postmenopausal women
Cytokine and Metabolomic Signatures of Mepolizumab Response Across Upper and Lower Airway Compartments in Severe Eosinophilic Asthma: An Exploratory Analysis
Background: Mepolizumab improves asthma control in severe eosinophilic asthma (SEA). However, its multidimensional effects on airway and systemic biomarkers are still incompletely understood. Methods: In this prospective study, 15 SEA patients were evaluated at baseline (T-0), 6 (T-6), and 12 months (T-12) after starting mepolizumab. Lung function, FeNO values, asthma control, blood eosinophil count (BEC), cytokines, and metabolomic profiles (H-1-NMR) were evaluated in serum, nasal secretions, and exhaled breath condensate (EBC). Univariate and multivariate (PCA, OPLS-DA) analyses were performed. Results: Mepolizumab reduced exacerbations, from a median of 2 at T-0 to 0 at both T-6 (p = 0.001) and T-12 (p = 0.003). ACT improved from 18.7 +/- 4.7 at baseline to 23.0 +/- 2.8 at T-6 (p = 0.026) and 23.4 +/- 3.3 at T-12 (p = 0.032), while FEV1 increased by 270 mL at T-6 (p = 0.032) and remained stable at T-12. Median BEC decreased from 450.0 (350.0-560.0) to 65.0 (50.0-87.5) cells/mu L at T-6 and to 50.0 (35.0-160.0) at T-12 (p < 0.001), while FeNO showed a non-significant downward trend. IL-13 significantly decreased in serum and nasal secretions at T-6 and T-12, while IL-5 increased in nasal secretions at both timepoints and remained unchanged in serum. IL-2 showed opposite trends in serum and nasal samples, whereas GM-CSF and IFN-gamma increased in nasal secretions at T-12. Metabolomic profiling suggested compartment-specific changes, with decreased short-chain alcohols in EBC, increased amino acids in nasal secretions and serum at T-6, and elevated pyruvate in serum at T-12, although none reached statistical significance in univariate analysis. Conclusions: Mepolizumab induced consistent clinical, immunologic, and metabolic changes across compartments, supporting the use of integrated cytokine and H-1-NMR metabolomic profiling as a complementary approach for response assessment in SEA
Determinants of 5-year survival in patients with advanced NSCLC with PD-L1≥50% treated with first-line pembrolizumab outside of clinical trials: results from the Pembro-real 5Y global registry
Background Pembrolizumab monotherapy is an established front-line treatment for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS)≥50%. However, real-world data on its long-term efficacy remains sparse. Methods This study assessed 5-year outcomes of first-line pembrolizumab monotherapy in a large, multicenter, real-world cohort of patients with advanced NSCLC and PD-L1 TPS≥50%, referred to as Pembro-real 5Y. Individual patient-level data (IPD) from the experimental arm of the KEYNOTE-024 trial were extracted (KN024 IPD cohort) to compare the long-term outcomes between the two cohorts. To further assess the reproducibility of clinical trial results, we reconstructed the "KN024 look-alike"cohort by excluding patients with an Eastern Cooperative Oncology Group-performance status (ECOG-PS)≥2, those requiring corticosteroids with doses ≥10 mg of prednisolone/equivalent, patients with positive/unknown epidermal growth factor receptor/anaplastic lymphoma kinase genotype, and those with pre-existing autoimmune disease. We additionally provided a hierarchical organization of determinants of long-term benefit through a conditional inference tree analysis. Results The study included 1050 patients from 61 institutions across 14 countries, with a median follow-up of 70.3 months. The 5-year survival rate was 26.9% (95% CI: 23.8% to 30.2%), and median OS was 21.8 months (95% CI: 19.1 to 25.7), while 32 (3.0%) patients who achieved a complete response remained progression-free at the data cut-off. The KN024 look-alike cohort had a 5-year survival rate of 29.3% (95% CI: 25.5% to 33.6%) and a median OS of 27.5 months (95% CI: 22.8 to 31.3). Neither the overall study population nor the KN024 look-alike cohort exhibited significantly different OS compared with the KN024 IPD cohort. By the data cut-off, 1015 patients (96.7%) had permanently discontinued treatment: 659 (64.9%) due to progressive disease, 156 (15.4%) due to toxicity, 77 (7.6%) due to treatment completion, and 106 (10.4%) due to other reasons. Overall, 222 participants (21.1%) were treated for a minimum period of 24 months, among them the 5-year survival rates were: 31.7%, 72.7%, 78.6%, 84.2% for patients who discontinued treatment due to progressive disease, toxicity, treatment completion, and other reasons, respectively. Conclusion This study provides valuable real-world evidence that confirms the long-term efficacy of pembrolizumab outside of clinical trials. Hierarchical organization indicates ECOG-PS, age and PD-L1-TPS as the most important predictors of 5-year survival, potentially informing clinical practice
Towards Precision Medicine in Sinonasal Tumors: Low-Dimensional Radiomic Signature Extraction from MRI
Background: Sinonasal tumors are rare, accounting for 3–5% of head and neck neoplasms. Machine learning (ML) and radiomics have shown promise in tumor classification, but current models lack detailed morphological and textural characterization. Methods: This study analyzed MRI data from 145 patients (76 malignant and 69 benign) across multiple centers. Radiomic features were extracted from T1-weighted (T1-w) images with contrast and T2-weighted (T2-w) images based on manually annotated tumor volumes. A dedicated ML pipeline assessed the effectiveness of different radiomic features and their integration with clinical variables. The DNetPRO algorithm was used to extract signatures combining radiomic and clinical data. Results: The results showed that ML classification using both data types achieved a median Matthews Correlation Coefficient (MCC) of 0.60 ± 0.07. The best-performing DNetPRO models reached an MCC of 0.73 (T1-w + T2-w) and 0.61 (T1-w only). Key clinical features included symptoms and tumor size, while radiomic features provided additional diagnostic insights, particularly regarding gray-level distribution in T2-w and texture complexity in T1-w images. Conclusions: Despite its potential, ML-based radiomics faces challenges in clinical adoption due to data variability and model diversity. Standardization and interpretability are crucial for reliability. The DNetPRO approach helps explain feature importance and relationships, reinforcing the clinical relevance of integrating radiomic and clinical data for sinonasal tumor classification
Survival and perioperative outcomes of pelvic exenteration in primary advanced and recurrent endometrial carcinoma: A systematic review and meta-analysis
Objective: To assess survival and perioperative complications and mortality of pelvic exenteration (PE) in recurrent and advanced endometrial carcinoma (EC) patients. Methods: A systematic review and a meta-analysis was performed searching 7 electronic databases from their inception to May 2024 for all peer-reviewed studies that reported as a study outcome at least the 5 years-overall survival (OS) of PE in recurrent and/or advanced EC patients.Our outcomes were 5 year-OS from PE as primary outcome, and all extractable outcomes about PE survival [overall OS, 5 year- and overall disease specific survival (DSS), 5 year- and overall progression free survival (PFS)] and perioperative mortality and complications.Rates of survival outcomes and perioperative mortality and complications were calculated as individual and pooled estimates, with 95 % confidence intervals (CI).Subgroup analyses were planned for all study outcomes based on recurrent or advanced EC, separately. Results: 6 studies with 166 patients were included. In women underwent PE for advanced or recurrent EC, pooled rate was: 41.7 % (95 % CI: 25.6–57.8 %) for 5 year-OS; 30.4 % (95 % CI: 14.9–45.8 %) for 5 year-DSS; 26.6 % (95 % CI: 10.6–42.5 %) for overall DSS; 51.8 % (95 % CI: 25.6–78.0 %) for 5 year-PFS; 9.7 % (95 % CI: 5.7–16.1 %) for perioperative mortality; 56.1 % (95 % CI: 32.3–76.4 %) for perioperative complications. Subgroup analyses were suitable exclusively in the “recurrent EC” subgroup and showed even worsened outcomes. Conclusions: In women with advanced or recurrent EC, PE shows not encouraging survival outcomes, with relatively high rates of perioperative mortality and complications. These outcomes further worsened in the subgroup of only recurrent EC. However, they should be confirmed by more updated studies
Correction: Ex situ germination of European acorns: data from 93 batches of 12 Quercus species (Annals of Forest Science, (2024), 81, (50), 10.1186/s13595-024-01267-2)
Following publication of the original article (Medina et al. 2024), the authors identified an error in the funding declaration. The originally published funding statement was: This research was funded by grant TRANS-ECO (TED2021-130976B-100) from Ministry of Science and Innovation/NextGeneration, grant RESISTRES (C-EXP267-UGR23) from University of Granada/Junta de Andalucía/FEDER, and grant RESTAURABIEN (RTI2018-096187-J-100) from the Spanish Ministry of Science, Innovation and Universities/FEDER, the PEN-CAFoRR (Pan-European Network for Climate Adaptive Forest Restoration and Reforestation) COST Action (European Cooperation in Science and Technology), and local funders for the fieldwork of each co-author. The updated funding statement is: This research was funded by grant TED2021-130976B-I00 funded by MICIU/AEI/10.13039/501100011033 and by the European Union Next GenerationEU/PRTR, grant RESISTRES (C-EXP267-UGR23) from University of Granada/Junta de Andalucía/FEDER, and grant RESTAURABIEN (RTI2018-096187-J-100) from the Spanish Ministry of Science, Innovation and Universities/FEDER, the PEN-CAFoRR (Pan-European Network for Climate Adaptive Forest Restoration and Reforestation) COST Action (European Cooperation in Science and Technology), and local funders for the fieldwork of each co-author. The original article (Medina et al. 2024) has been corrected