Archivio istituzionale della ricerca - Università dell'Insubria
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Modeling large cell neuroendocrine carcinoma of the lung for molecular, therapeutic and microenvironmental inferences: current knowledge and future perspectives
No full textIntroduction: Large cell neuroendocrine carcinoma (LCNEC) of the lung is a high-grade non-small cell carcinoma featuring neuroendocrine morphology and neuroendocrine markers. Despite being credited since decades as an independent tumor entity, it continues to represent a diagnostic and therapeutic challenge probably because makes up a heterogeneous melting pot of genetic and epigenetic alterations closely intertwined with host microenvironment. Areas covered: LCNEC of the lung was untangled according to three converging outlooks: (i) diagnostic criteria and molecular alterations as conveyors of pathogenetic diversification; (ii) microenvironmental changes, including immune system, as culprits behind tumor development; and (iii) available clinical trials, including immune-oncology studies as clinical decision-making drivers. Expert opinion: LCNEC of the lung unveils different developmental trajectories, which may account for troubles in diagnosis and clinical decision-making but, at the same time, offer a rationale for personalized targeted treatments or immunotherapy in patient subsets. Currently, the question is fascinating: are we actually ready for a radical route change in the understanding of LCNEC? The answer is still open, but future studies will need to frame LCNEC in its own overarching context among lung cancers according to a holistic vision, which does not limit us to its perception as being ‘just one tumor.’
Intravenous Amino-acid Infusion to Prevent Acute Kidney Injury after Cardiac Surgery: A Review of the Evidence
No full textBackground: Acute kidney injury (AKI) is a frequent and important complication of cardiac surgery. Decreased perfusion is a key mechanism. This decreased perfusion may be attenuated by intravenous amino acids (AAs) through recruitment of renal functional reserve. Methods: The study investigators performed a PubMed search of all articles published from 1980 to August 30, 2024, with combined search criteria of “renal functional reserve,” “amino acids,” “cardiac surgery,” and “cardiopulmonary bypass” by using MEDLINE (PubMed), Embase, and the Cochrane Central Register of Clinical Trials. Included were studies describing the effect of AAs on renal functional reserve and studies of adult cardiac surgery patients with information on renal function. A narrative review was developed. Results: Multiple experimental and human studies over >40 years have recurrently and consistently shown that the administration of an oral protein load or intravenous AAs increase renal blood flow and glomerular filtration rate by >30%. Moreover, several pilot investigations in cardiac surgery with cardiopulmonary bypass consistently showed renal benefits with intravenous AAs. Finally, a pivotal trial of 3511 cardiac surgery patients (the PROTECTION trial) recently confirmed such beneficial effects in a double-blind multicenter international setting. Conclusions: Intravenous AAs consistently recruit renal functional reserve and improve kidney function in cardiac surgery patients. These findings have been confirmed by the PROTECTION (Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery) trial. Intravenous AA therapy is the only proven treatment to prevent and/or attenuate the severity of cardiac surgery−associated AKI
Biomarker testing implementation for molecularly targeted therapy in non-small cell lung cancer patients
No full textBackground: Recent advancements in identifying druggable molecular drivers in lung adenocarcinoma (LUAD), have transformed treatment paradigms. In recent years, Next Generation Sequencing (NGS) has gained momentum as an essential tool for in-depth simultaneous analysis of multiple genes, thereby streamlining the diagnostic process in LUAD. Despite this, the implementation of NGS testing in both the US and Europe remains suboptimal. Aims: In compliance with a decree issued by the Italian Ministry of Health, Lombardy Region recently launched an initiative to implement NGS testing in patients with advanced LUAD. In this context, a real-world prospective observational study was planned to assess the efficacy of the regional network of molecular laboratories in testing nine biomarkers (KRAS p.G12C, EGFR, BRAF, HER2, MET mutations; ALK, ROS1, NTRK1-3, RET rearrangements), for on-label molecularly targeted drugs. Results: In 2023, out of the 2784 advanced/metastatic LUAD patients expected in Lombardy, 2343 (84.2%) were successfully evaluated with an NGS panel including all the nine biomarkers for on-label drugs. Actionable aberrations were identified in 45.5% of the patients (1068/2343), predominantly involving EGFR, KRAS, and ALK genes. Conclusion: Our data provide evidence that establishing a structured network of NGS hubs is mandatory to ensure access of advanced LUAD patients to molecularly targeted treatments
Come grida manzoniane. Esempi di costituzioni tardoimperiali contro il vagabondaggio e l’iniuria potentium
No full textIl contributo si occupa del ruolo del defensor civitatis in epoca tardoantica, in particolare durante il regno di Teodosio I. La trasformazione del defensor
in un funzionario di nomina locale da parte delle curie, con
competenze sempre maggiori in campo fiscale, amministrativo e
addirittura giudiziario. La stessa inefficacia dei provvedimenti nei
confronti dei latrones alle dipendenze di potentiores locali caratterizza
le grida aventi ad oggetto i “bravi” e i loro protettori, di cui si
fa beffe Alessandro Manzoni nell’apertura dei Promessi Sposi: non si
tratta di cadere nel pericoloso quanto suggestivo trabocchetto dei
corsi e ricorsi storici, ma di cogliere i tratti ricorrenti di un fenomeno
sociale che percorse la storia europea dagli albori del Medioevo
fino alla sua coda alle soglie dell’età moderna
Tirbanibulin 1% real-world use in 679 actinic keratoses patients during warm season (SUMM-AK study)
Get PDFRadioprotection-based cephalometric analysis: validation of AB-ratio for sagittal assessment of malocclusion
No full textObjective: This study aimed to validate the AB-ratio metric, a novel 3D cephalometric tool for assessing skeletal malocclusions, and to evaluate its reliability in comparison to the traditional ANB angle and Wits appraisal, with a focus on minimizing radiation exposure in orthodontic diagnostics. Methods: A retrospective CBCT analysis was conducted on 352 full-cranium scans. Twelve anatomical landmarks were manually annotated. ANB (°), Wits (mm) and AB-ratio were calculated. Following the assessment of data non-normality using the Shapiro-Wilk test and the removal of outliers via Tukey's fences, statistical analyses were conducted using Spearman's rank correlation coefficient (ρ) and Kendall's tau (τ) to evaluate associations. Additionally, the Siegel non- parametric linear regression estimator was applied to assess the relationships between AB-ratio and ANB, as well as between AB-ratio and Wits. Cohen's kappa coefficient (κ) and percentage of agreement also evaluated the contingency between methods. Significance (p) was set at 0.05. Results: A strong and significant correlation (ρ=0.787; τ=0.569; p < 0.001) was found between the AB-ratio and ANB angle while a moderate correlation was reported between AB-ratio and Wits (ρ=0.733; τ=0.551; p < 0.001). Linear regressions provided the following equations: AB-ratio=0.04*ANB+0.76 and AB-ratio=0.03*Wits+0.99. The κ scores of diagnostic concordances between AB-ratio and ANB and Wits were 0.562 and 0.089, respectively, showing different agreements (75.44% vs 31.67%). All tests comparing ANB and Wits showed lower correlations (ρ=0.659; τ=0.484) and agreement (κ =0.042; 29.89%). Conclusions: The AB-ratio metric might significantly enhance 3D cephalometric analysis by providing reliable assessments of skeletal malocclusions while adhering to radioprotection principles. The AB-ratio classified sagittal discrepancies with norms of 0.84±0.08 for Class I, <0.76 for Class III, and >0.92 for Class II malocclusions. Clinical significance: The AB-ratio offers a reliable 3D alternative to the ANB angle and Wits appraisal for diagnosing skeletal malocclusions, with strong and moderate correlation and moderate and poor classification agreement, respectively
Fra memoria e heritage: la spazializzazione del passato in Terra santa (e la scoperta dello spazio sociale di Maurice Halbwachs)
No full textIl contributo riflette sulla relazione fra heritage e memoria a partire dagli studi di Halbwachs sulla
memoria collettiva. Il tema della memoria occupa una posizione piuttosto marginale negli studi sul patrimonio, le
due nozioni tendono talvolta a sovrapporsi o a coincidere, e la memoria finisce per essere data per scontata. L’articolo:
a) illustra le geografie della memoria collettiva negli studi pionieri di Halbwachs, che riconosce allo spazio socializzato
un’importanza fondamentale nella produzione e nel consolidamento delle memorie e delle identità sociali; b) approfondisce
la spazializzazione della memoria in Terra santa, rileggendo una memoria di viaggio familiare alla luce degli studi di
Halbwachs sulla produzione storica dei Luoghi santi in Palestina e a Gerusalemme: c) offre alcune considerazioni finali
sul rapporto per nulla lineare fra heritage e memoria, sostenendo che le porzioni di “memoria collettiva” che un certo
gruppo sociale in un certo momento storico distilla come particolarmente significative per la propria identità di gruppo,
ne costituiscono il “patrimonio” che per ciò stesso viene rappresentato come prova della propria esistenza e originalità
Environmental formation of sulfonated-PCBs and OH-sulfonated-PCBs: Is it greater under aerobic or anaerobic conditions?
Get PDFThe aerobic and anaerobic degradation of PCBs is well documented in literature. On the other hand, OH-sulfonated- and sulfonated-PCBs are newly discovered metabolites, therefore, little information is known about their fate in the environment. For instance, their formation in anaerobic conditions was never investigated. In the current paper, aerobic, anaerobic-aerobic (two steps mode) and anaerobic treatments were set up to compare for the first time the OH-, OH-sulfonated- and sulfonated-PCB production in different oxic and anoxic conditions. For this purpose, leaves of Quercus ilex were used as microbial inoculum in 40 mL vials spiked with PCB 155 used as individual contaminant. In general, all three classes were produced in every condition. The aerobic treatment was the best one, as the highest concentrations and number of congeners were detected. Then, the more oxygen decreases, the lower the concentration of metabolites formed: aerobiosis > anaerobiosis-aerobiosis > anaerobiosis. In addition, the same chlorination families for each class were formed, except for the anaerobiosis-aerobiosis treatment, where a hexa-Cl-sulfonated-PCB was also detected