34 research outputs found
The strange connection between epidermal growth factor receptor tyrosine kinase inhibitors and dapsone: from rash mitigation to the increase in anti-tumor activity
No full textThe presence of an aberrantly activated epidermal growth factor receptor (EGFR) in many epithelial tumors, due to its overexpression, activating mutations, gene amplification and/or overexpression of receptor ligands, represent the fundamental basis underlying the use of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Drugs inhibiting the EGFR have different mechanisms of action; while erlotinib and gefitinib inhibit the intracellular tyrosine kinase, monoclonal antibodies like cetuximab and panitumumab bind the extracellular domain of the EGFR both activating immunomediated anti-cancer effect and inhibiting receptor function. On the other hand, interleukin-8 has tumor promoting as well as neo-angiogenesis enhancing effects and several attempts have been made to inhibit its activity. One of these is based on the use of the old sulfone antibiotic dapsone that has demonstrated several interleukin-8 system inhibiting actions. Erlotinib typically gives a rash that has recently been proven to come out via up-regulated keratinocyte interleukin-8 synthesis with histological features reminiscent of typical neutrophilic dermatoses. In this review, we report experimental evidence that shows the use of dapsone to improve quality of life in erlotinib-treated patients by ameliorating rash as well as short-circuiting a growth-enhancing aspect of erlotinib based on increased interleukin-8 secretion.The presence of an aberrantly activated epidermal growth factor receptor (EGFR) in many epithelial tumors, due to its overexpression, activating mutations, gene amplification and/or overexpression of receptor ligands, represent the fundamental basis underlying the use of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Drugs inhibiting the EGFR have different mechanisms of action; while erlotinib and gefitinib inhibit the intracellular tyrosine kinase, monoclonal antibodies like cetuximab and panitumumab bind the extracellular domain of the EGFR both activating immunomediated anti-cancer effect and inhibiting receptor function. On the other hand, interleukin-8 has tumor promoting as well as neo-angiogenesis enhancing effects and several attempts have been made to inhibit its activity. One of these is based on the use of the old sulfone antibiotic dapsone that has demonstrated several interleukin-8 system inhibiting actions. Erlotinib typically gives a rash that has recently been proven to come out via up-regulated keratinocyte interleukin-8 synthesis with histological features reminiscent of typical neutrophilic dermatoses. In this review, we report experimental evidence that shows the use of dapsone to improve quality of life in erlotinib-treated patients by ameliorating rash as well as short-circuiting a growth-enhancing aspect of erlotinib based on increased interleukin-8 secretion
Etnografia digitale, netnografia e autoetnografia: ricerche tra vecchi punk, giovani neopagani e membri di una vasta comunità BDSM della Repubblica ceca
No full textIl capitolo presenta l'esperienza personale dell'autore, con l'utilizzo dei dati e delle esperienze raccolte attraverso internet, la netnografia come forma di ricerca qualitativa e l'accettazione personale dell'autoetnografia per la comprensione di sé, dell'altro e della cultura. Saranno analizzati 12 studi e ricerche realizzate dallo stesso autore, da solo o in qualità di coautore, tra gli anni 2005 e 2019, su temi di ricerca differenti, ma concentrati su selezionate sottoculture attive nella Repubblica Ceca. Il capitolo è concepito come un'introspezione diacronica in cui l'autore descrive i suoi primi tentativi di utilizzare pagine web e discussioni in internet come fonte di citazioni in articoli scientifici, fino al raggiungimento di una metodologia netnografica più matura.The chapter presents the personal experience of the author, with the use of data and experiences collected through the internet, the netnography as a form of qualitative research, and the personal acceptance of the autoethnography for the understanding of self, other, and culture. It will be analyzed 12 studies and researches realized by the same author, alone or as co-author, between the years 2005 and 2019, on different, but connected research topics concentred on selected sub-cultures active in the Czech Republic. The chapter is conceived as a diachronic introspection where the author describes his first attempts to use web pages and internet discussions as a source of quotations in scientific papers, up to the achievement of a more mature netnographic methodology
Cardiomyopathy and sudden cardiac death: bridging clinical practice with cutting-edge research
No full textSudden cardiac death (SCD) prevention in cardiomyopathies such as hypertrophic (HCM), dilated (DCM), non-dilated left ventricular (NDLCM), and arrhythmogenic right ventricular car- diomyopathy (ARVC) remains a crucial but complex clinical challenge, especially among younger populations. Accurate risk stratification is hampered by the variability in phenotypic expression and genetic heterogeneity inherent in these conditions. This article explores the multifaceted strategies for preventing SCD across a spectrum of cardiomyopathies and emphasizes the integration of clinical evaluations, genetic insights, and advanced imaging techniques such as cardiac magnetic resonance (CMR) in assessing SCD risks. Advanced imaging, particularly CMR, not only enhances our under- standing of myocardial architecture but also serves as a cornerstone for identifying at-risk patients. The integration of new research findings with current practices is essential for advancing patient care and improving survival rates among those at the highest risk of SCD. This review calls for ongoing research to refine risk stratification models and enhance the predictive accuracy of both clinical and imaging techniques in the management of cardiomyopathies
Author Correction: EGFR and HER2 exon 20 insertions in solid tumours: from biology to treatment (Nature Reviews Clinical Oncology, (2022), 19, 1, (51-69), 10.1038/s41571-021-00558-1)
No full textAppropriate ICD Interventions for Ventricular Arrhythmias Are Predicted by Higher Syntax Scores I and II in Patients with Ischemic Heart Disease
No full textThe occurrence of ventricular arrhythmias (VAs) in ischemic heart disease (IHD) patients is related to the presence and extent of fibrotic/scar tissue. As coronary atherosclerosis is the underlying cause of myocardial ischemia and fibrosis, in IHD patients implanted with an implantable cardioverter defibrillator (ICD) we investigated the relation between the VA burden and the complexity of coronary atherosclerotic lesions
Endocardial Ablation of Atrial Flutter with Involvement of the Vein of Marshall: A Case Report
No full text: Background: Atypical atrial flutter (AFL) is a complex clinical challenge, particularly in patients with prior atrial fibrillation (AF) treated with pulmonary vein isolation (PVI). Arrhythmias involving the vein of Marshall (VOM) often require extensive lesion sets, including ethanol infusion, to effectively target the epicardial substrate. To minimize tissue damage, an alternative strategy has been proposed, emphasizing advanced electroanatomical mapping, entrainment maneuvers, and highly targeted ablation techniques. Case Presentation: We describe a 72-year-old woman with recurrent atrial arrhythmias following pulmonary vein isolation (PVI), who presented with palpitations as her primary symptom. After ineffective pharmacological therapy, she underwent a catheter ablation procedure. Electroanatomical mapping revealed significant left atrial scarring and suggested a macroreentrant circuit involving the VOM. Entrainment maneuvers confirmed the VOM's involvement. A single targeted endocardial ablation guided by the ablation index terminated the arrhythmia within 12 s, without the need for ethanol infusion or extensive lesion sets. Discussion: This case underscores the VOM's role in sustaining atypical AFL post-PVI and highlights the effectiveness of precise electroanatomical mapping combined with targeted endocardial ablation. Unlike broader ablation or ethanol infusion strategies, a focused lesion at the critical isthmus achieved arrhythmia termination with minimal tissue damage. Conclusions: Endocardial ablation at the site of entrainment can safely and effectively treat VOM-related AFL, offering symptom relief and restoration of sinus rhythm. This approach may reduce procedural risks and expand the feasibility of VOM-related arrhythmia management in centers without access to ethanol infusion
Patient with Vulnerable Coronary Plaque and Treatment with Evolocumab: A Clinical Case
No full textBackground/Objectives: Vulnerable coronary plaques are strongly associated with acute coronary events, posing significant therapeutic challenges despite statin therapy. This case report evaluates the impact of Evolocumab, a PCSK-9 inhibitor, on stabilizing high-risk plaques and promoting phenotypic transformation, assessed through coronary CT angiography (CCTA). Methods: A 50-year-old male with chronic coronary syndrome and a history of myocardial infarction underwent a CCTA, revealing a high-risk plaque (approximately 50%) in the proximal LAD. Despite achieving LDL-C targets with statin therapy, the plaque showed vulnerability features. Evolocumab (140 mg subcutaneously every two weeks) was added to therapy, combined with dietary counseling and dual antiplatelet therapy. Results: A follow-up CCTA at 24 months demonstrated significant reductions in plaque volume and positive remodeling, with a transformation from a mixed phenotype to a predominantly calcified plaque. LDL-C levels decreased from 71 mg/dL to 18 mg/dL. The patient remained asymptomatic, with no cardiovascular events reported during the follow-up. Conclusions: This case highlights the role of PCSK-9 inhibitors in stabilizing high-risk plaques, achieving structural changes that promote stability beyond LDL-C reduction. Advanced imaging techniques such as CCTA proved essential for risk stratification and monitoring therapy efficacy. Evolocumab offers a promising adjunctive treatment for high-risk patients unsuitable for elective revascularization, potentially redefining the standard of care for plaque stabilization in this setting
A new schedule of fotemustine in temozolomide-pretreated patients with relapsing glioblastoma
No full textIn the present study we investigated the feasibility and effectiveness of a new biweekly schedule of fotemustine (FTM) in patients with recurrent glioblastoma, after at least one previous treatment. The primary endpoint was progression-free survival at 6 months; secondary objectives were clinical response, overall survival, disease-free survival, and toxicity. Forty patients (median age 52.8 years; median Karnofsky Performance Status at progression 90) underwent second-line chemotherapy with FTM. Selected patients were previously treated with a standard radiotherapy course with concomitant temozolomide (TMZ). After tumor relapse or progression proven by magnetic resonance imaging (MRI), all patients underwent chemotherapy with FTM, given intravenously at dose of 80 mg/m2 every 2 weeks for five consecutive administrations (induction phase), and then every 3 weeks at 100 mg/m2 as maintenance. A total of 329 infusions were administered; the median number of cycles administered was 8. All patients completed the induction phase, and 29 patients received at least one maintenance infusion. Response to treatment was assessed using MacDonald criteria. One complete response [2.5%, 95% confidence interval (CI): 0-10%], 9 partial responses (22.5%, 95% CI: 15-37%), and 16 stable diseases (40%, 95% CI: 32-51%) were observed. Median time to progression was 6.7 months (95% CI: 3.9-9.1 months). Progression-free survival at 6 months was 61%. Median survival from beginning of FTM chemotherapy was 11.1 months. The schedule was generally well tolerated; the main toxicities were hematologic (grade 3 thrombocytopenia in two cases). To the best of our knowledge, this is the first report specifically dealing with the use of a biweekly induction schedule of FTM. The study demonstrates that FTM has therapeutic efficacy as single-drug second-line chemotherapy with a favorable safety profile. © 2010 The Author(s).In the present study we investigated the feasibility and effectiveness of a new biweekly schedule of fotemustine (FTM) in patients with recurrent glioblastoma, after at least one previous treatment. The primary endpoint was progression-free survival at 6 months; secondary objectives were clinical response, overall survival, disease-free survival, and toxicity. Forty patients (median age 52.8 years; median Karnofsky Performance Status at progression 90) underwent second-line chemotherapy with FTM. Selected patients were previously treated with a standard radiotherapy course with concomitant temozolomide (TMZ). After tumor relapse or progression proven by magnetic resonance imaging (MRI), all patients underwent chemotherapy with FTM, given intravenously at dose of 80 mg/m2 every 2 weeks for five consecutive administrations (induction phase), and then every 3 weeks at 100 mg/m2 as maintenance. A total of 329 infusions were administered; the median number of cycles administered was 8. All patients completed the induction phase, and 29 patients received at least one maintenance infusion. Response to treatment was assessed using MacDonald criteria. One complete response [2.5%, 95% confidence interval (CI): 0-10%], 9 partial responses (22.5%, 95% CI: 15-37%), and 16 stable diseases (40%, 95% CI: 32-51%) were observed. Median time to progression was 6.7 months (95% CI: 3.9-9.1 months). Progression-free survival at 6 months was 61%. Median survival from beginning of FTM chemotherapy was 11.1 months. The schedule was generally well tolerated; the main toxicities were hematologic (grade 3 thrombocytopenia in two cases). To the best of our knowledge, this is the first report specifically dealing with the use of a biweekly induction schedule of FTM. The study demonstrates that FTM has therapeutic efficacy as single-drug second-line chemotherapy with a favorable safety profile. © 2010 The Author(s)
La netnografia. Strumenti e tecniche per la ricerca etnografica online
No full text2014 - 2015L’obiettivo del presente contributo è indagare, da un punto di vista eminentemente metodologico, la
netnografia, evidenziando opportunità e limiti del suo utilizzo nell’ambito della ricerca sociale.
Dopo aver illustrato le motivazioni alla base della necessità di sviluppare un approccio di ricerca
innovativo e specifico per lo studio delle comunicazioni ed interazioni che avvengono attraverso
Internet, il lavoro procede alla definizione dell’approccio netnografico e all’individuazione dei suoi
principali ambiti di applicazione.
Successivamente, vengono illustrate le origini della netnografia, evidenziando similarità e
differenze con l’etnografia tradizionale.
I capitoli centrali del lavoro sono dedicati alla presentazione delle singole fasi di svolgimento di una
ricerca netnografica, dalla definizione degli obiettivi cognitivi alla redazione del rapporto finale di
ricerca.
Nel corso di questi capitoli, sono evidenziate le principali questioni metodologiche e, soprattutto, le
sfide poste al ricercatore sociale dalla trasposizione online e dalla conseguente necessità di
riconfigurazione di alcuni concetti fondamentali della ricerca etnografica (viaggio, campo, raccolta,
osservazione).
Il lavoro richiama l’attenzione sulle questioni connesse alle strategie di presentazione del
ricercatore, con particolare riferimento alla possibilità di condurre una ricerca completamente
coperta (lurking), evidenziando vantaggi e limiti di questa opzione. Nella tesi viene, poi,
approfondito il concetto di partecipazione illustrando i diversi gradi e le differenti forme che essa
può assumere durante lo svolgimento di un’indagine netnografica e proponendone una tipologia.
Un intero capitolo del lavoro è dedicato ai criteri di controllo da esercitare per valutare la bontà
della ricerca prodotta (conformità, congruenza) e al problema della generalizzabilità dei risultati di
una ricerca netnografica.
Nella parte finale del lavoro vengono presentate due ricerche empiriche, basate sull’applicazione
della netnografia, che riguardano due comunità di pratica associate alla fruizione appassionata di
prodotti mediali.
I due casi di studio, oltre che interessanti dal punto di vista sostantivo, forniscono esempi concreti di
applicazione delle questioni metodologiche delineate nei capitoli precedenti del lavoro. [a cura dell'Autore]The aim of this work is to investigate, from a methodological point of view, the netnographic
approach, highlighting opportunities and limits of its use for social research.
After explaining the reasons why social researchers need to develop an innovative and specific
approach in order to study communications and interactions that occur through the Internet, the
work provides a definition of netnography identifying its distinctive features and its main areas of
interest.
Subsequently, the work describes the origins of netnography, highlighting similarities and
differences with traditional ethnography.
The central chapters of the thesis are aimed at presenting the different steps for conducting a
netnographic research, from the definition of the research aim and questions to the editing of the
final research report. Within these chapters, the main methodological issues related to netnography
are presented, underlining the importance of redefining some fundamental concepts of ethnographic
research (such as travel, field, data collection and observation).
The work is focused, in particular, on the issues of researcher's presentation, examining the
possibility of conducting a fully covered research (lurking) and highlighting advantages and
limitations of this option. Moreover, the concept of participation is analysed in depth, illustrating
the different degrees and forms that it can assume during a netnographic investigation.
An entire chapter of the thesis is focused on the criteria for assessing the trustworthiness of research
(conformity, congruence) and on the issue of generalizing results.
In the final part of the work, two empirical research based on netnography are shown. These two
case studies provide concrete examples of application of the methodological issues outlined in the
previous chapters. [edited by Author]XIV n.s
