50 research outputs found

    First report outside Eastern Europe of West Nile virus lineage 2 related to the Volgograd 2007 strain, northeastern Italy, 2014

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    open11noWest Nile virus (WNV) is a Flavivirus transmitted to vertebrate hosts by mosquitoes, maintained in nature through an enzootic bird-mosquito cycle. In Europe the virus became of major public health and veterinary concern in the 1990s. In Italy, WNV re-emerged in 2008, ten years after the previous outbreak and is currently endemic in many areas of the country. In particular, the northeastern part of Italy experience continuous viral circulation, with human outbreaks caused by different genovariants of WNV lineage 1, Western-European and Mediterranean subcluster, and WNV lineage 2, Hungarian clade. Alongside the WNV National Surveillance Program that has been in place since 2002, regional surveillance plans were implemented after 2008 targeting mosquitoes, animals and humans.openRavagnan, Silvia; Montarsi, Fabrizio; Cazzin, Stefania; Porcellato, Elena; Russo, Francesca; Palei, Manlio; Monne, Isabella; Savini, Giovanni; Marangon, Stefano; Barzon, Luisa; Capelli, GioiaRavagnan, Silvia; Montarsi, Fabrizio; Cazzin, Stefania; Porcellato, Elena; Russo, Francesca; Palei, Manlio; Monne, Isabella; Savini, Giovanni; Marangon, Stefano; Barzon, Luisa; Capelli, Gioi

    Label-Free Quantification of Anticancer Drug Imatinib in Human Plasma with Surface Enhanced Raman Spectroscopy

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    Therapeutic drug monitoring (TDM) for anticancer drug imatinib has been suggested as the best way to improve the treatment response and minimize the risk of adverse reactions in chronic myelogenous leukemia (CML) and gastrointestinal stromal tumor (GIST) patients. TDM of oncology treatments with standard analytical methods, such as liquid chromatography-tandem mass spectrometry (LC-MS/ MS) is, however, complex and demanding. This paper proposes a new method for quantitation of imatinib in human plasma, based on surface enhanced raman spectroscopy (SERS) and multivariate calibration using partial least-squares regression (PLSR). The best PLSR model was obtained with three latent variables in the range from 123 to 5000 ng/mL of imatinib, providing a standard error of prediction (SEP) of 510 ng/mL. The method was validated in accordance with international guidelines, through the estimate of figures of merit, such as precision, accuracy, systematic error, analytical sensitivity, limits of detection, and quantitation. Moreover, the feasibility and clinical utility of this approach have also been verified using real plasma samples taken from deidentified patients. The results were in good agreement with a clinically validated LC-MS/MS method. The new SERS method presented in this preliminary work showed simplicity, short analysis time, good sensitivity, and could be considered a promising platform for TDM of imatinib treatment in a point-of-care setting

    Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

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    Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

    Impact of dysgeusia on nutritional status in cancer patients undergoing autologous hematopoietic stem cell transplantation (HSCT)

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    openLa patologia oncologica rappresenta una delle patologie croniche con la maggior prevalenza di malnutrizione calorico-proteica, in particolare stimata da tra il 20 e il 70%. Le patologie oncologiche a più elevata prevalenza di malnutrizione sono quelle che interessano l’apparato gastrointestinale, il distretto testa-collo e il polmone, vista la sede di malattia e le caratteristiche metaboliche della neoplasia. Tra gli effetti collaterali delle terapie, quelli che impattano sulla sfera nutrizionale e che sono di più frequente riscontro sono inappetenza, nausea e vomito. La disgeusia è un aspetto ancora non molto analizzato. Parimenti, patologie quali le patologie ematologiche e della linea germinale presentano un minor tasso di malnutrizione. Anche in questo ambito, i dati in letteratura sono carenti. L’obiettivo di questa tesi è valutare lo stato nutrizionale nei pazienti che vengono sottoposti a trapianto autologo di midollo e i rapporti con la disgeusia. Sono stati inclusi tutti i pazienti sottoposti a trapianto autologo di CSE presso l’Istituto Oncologico Veneto, nel periodo che va da giugno a novembre 2023. Tutti i pazienti sono stati valutati mediante rilevazione di parametri antropometrici (peso e altezza, calcolo del BMI), test di screening NRS 2002, analisi della composizione corporea tramite bioimpedenziometria e valutazione della forza dell’arto superiore non dominante mediante dinamometro hand-grip. È stato somministrato il questionario CiTAS per valutare la disgeusia ed è stata effettuata una stima degli introiti per os mediante Recall 24h. Lo studio ha coinvolto 5 soggetti, con età media di 57 anni, con tempo di degenza medio di 3 settimane e mezzo. Durante la degenza in stanza a bassa carica microbica si è rilevato un calo ponderale rispetto all’ingresso mediamente di 7,2 kg (- 8.5%, pari al 12,6% nelle femmine e al 6% nei maschi); si è rilevata una riduzione anche dell’angolo di fase pari in media a 0,9°; non si è rilevata una riduzione di massa magra nei maschi, mentre le femmine hanno presentato un calo medio di 1,9 kg/mq. Per quanto riguarda la misurazione dell’hand-grip, è risultato diminuito sia nei maschi, che nelle femmine. L’introito calorico alla dimissione era diminuito del 43% rispetto all’ingresso, mentre quello proteico si presentava diminuito del 20% circa. Tutti i valori riscontrati hanno evidenziato un peggioramento dello stato nutrizionale, infatti all’arruolamento solo il 20% dei pazienti era a rischio nutrizionale secondo il test di screening NRS 2002, mentre alla dimissione il 100% del campione era a rischio. Utilizzando i criteri GLIM per valutare l’effettiva presenza di malnutrizione, questa è stata riscontrata di grado moderato nei maschi e severo nelle femmine. Andando a valutare i valori risultanti dal questionario CiTAS, è emerso come questi siano fortemente aumentati nelle fasi centrali della degenza, contestualmente al periodo in cui si è ricavato l’introito calorico-proteico più basso, risultando alla dimissione più elevati di 1,4 punti rispetto alla prima valutazione, evidenziando un peggioramento della disgeusia. In particolare, poi, si è visto come il punteggio del CiTAS correli in modo significativo e direttamente proporzionale con la diminuzione degli introiti calorici, mentre non sembra esserci significatività nella correlazione tra CiTAS e calo ponderale o introiti proteici. Possiamo concludere, a seguito di questo lavoro, che il trapianto autologo di CSE porti ad un’alterazione dello stato nutrizionale, e che questa possa essere influenzata dalla disgeusia e dagli scarsi introiti calorici con cui essa correla fortemente. È importante sottolineare come sia fondamentale il riconoscimento precoce della malnutrizione in questi soggetti, affinché possano essere seguiti anche dal punto di vista nutrizionale, prevenendo le conseguenze della malnutrizione

    Fluorescent Imprinted Nanoparticles for the Effective Monitoring of Irinotecan in Human Plasma

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    Fluorescent, imprinted nanosized polymers for the detection of irinotecan have been synthesised using a napthalimide polymerisable derivative (2-allyl-6-[2-(aminoethyl)-amino] napthalimide) as functional monomer. The imprinted polymers contain ethylene glycol dimethacrylate (EGDMA) as a cross-linker and were prepared by high dilution radical polymerisation in dimethylsulphoxide (DMSO). The material was able to rebind irinotecan up to 18 nmol/mg with good specificity. Fluorescence emission at 525 nm (excitation at 448 nm) was quenched by increasing concentrations of irinotecan via a static mechanism and also in analytically useful environments as mixtures of human plasma and organic solvents. This allowed the direct detection of irinotecan (in the 10 nM-30 \ub5M range) in human plasma treated with acetonitrile; the limit of detection (LOD) was 9.4 nM, with within-run variability of 10% and day-to-day variability of 13%

    Development and Validation of a High- Performance Liquid Chromatography– Tandem Mass Spectrometry Method for the Simultaneous Determination of Irinotecan and Its Main Metabolites in Human Plasma and Its Application in a Clinical Pharmacokinetic Study

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    Irinotecan is currently used in several cancer regimens mainly in colorectal cancer (CRC). This drug has a narrow therapeutic range and treatment can lead to side effects, mainly neutropenia and diarrhea, frequently requiring discontinuing or lowering the drug dose. A wide inter-individual variability in irinotecan pharmacokinetic parameters and pharmacodynamics has been reported and associated to patients’ genetic background. In particular, a polymorphism in the UGT1A1 gene (UGT1A1*28) has been linked to an impaired detoxification of SN-38 (irinotecan active metabolite) to SN-38 glucuronide (SN-38G) leading to increased toxicities. Therefore, therapeutic drug monitoring of irinotecan, SN-38 and SN-38G is recommended to personalize therapy. In order to quantify simultaneously irinotecan and its main metabolites in patients’ plasma, we developed and validated a new, sensitive and specific HPLC–MS/MS method applicable to all irinotecan dosages used in clinic. This method required a small plasma volume, addition of camptothecin as internal standard and simple protein precipitation. Chromatographic separation was done on a Gemini C18 column (3 ÎŒM, 100 mm x 2.0 mm) using 0.1% acetic acid/bidistilled water and 0.1% acetic acid/acetonitrile as mobile phases. The mass spectrometer worked with electrospray ionization in positive ion mode and selected reaction monitoring. The standard curves were linear (R20.9962) over the concentration ranges (10–10000 ng/mL for irinotecan, 1–500 ng/mL for SN-38 and SN-38G and 1–5000 ng/mL for APC) and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy, determined on three quality control levels for all the analytes, were always <12.3% and between 89.4% and 113.0%, respectively. Moreover, we evaluated this bioanalytical method by re-analysis of incurred samples as an additional measure of assay reproducibility. This method wassuccessfully applied to a pharmacokinetic study in metastatic CRC patients enrolled in a genotype-guided phase Ib study of irinotecan administered in combination with 5-fluorouracil/ leucovorin and bevacizumab

    Development and Validation of a High-Performance Liquid Chromatography–Tandem Mass Spectrometry Method for the Simultaneous Determination of Irinotecan and Its Main Metabolites in Human Plasma and Its Application in a Clinical Pharmacokinetic Study

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    <div><p>Irinotecan is currently used in several cancer regimens mainly in colorectal cancer (CRC). This drug has a narrow therapeutic range and treatment can lead to side effects, mainly neutropenia and diarrhea, frequently requiring discontinuing or lowering the drug dose. A wide inter-individual variability in irinotecan pharmacokinetic parameters and pharmacodynamics has been reported and associated to patients’ genetic background. In particular, a polymorphism in the <i>UGT1A1</i> gene (<i>UGT1A1*28</i>) has been linked to an impaired detoxification of SN-38 (irinotecan active metabolite) to SN-38 glucuronide (SN-38G) leading to increased toxicities. Therefore, therapeutic drug monitoring of irinotecan, SN-38 and SN-38G is recommended to personalize therapy. In order to quantify simultaneously irinotecan and its main metabolites in patients’ plasma, we developed and validated a new, sensitive and specific HPLC–MS/MS method applicable to all irinotecan dosages used in clinic. This method required a small plasma volume, addition of camptothecin as internal standard and simple protein precipitation. Chromatographic separation was done on a Gemini C18 column (3 ÎŒM, 100 mm x 2.0 mm) using 0.1% acetic acid/bidistilled water and 0.1% acetic acid/acetonitrile as mobile phases. The mass spectrometer worked with electrospray ionization in positive ion mode and selected reaction monitoring. The standard curves were linear (R<sup>2</sup> ≄0.9962) over the concentration ranges (10–10000 ng/mL for irinotecan, 1–500 ng/mL for SN-38 and SN-38G and 1–5000 ng/mL for APC) and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy, determined on three quality control levels for all the analytes, were always <12.3% and between 89.4% and 113.0%, respectively. Moreover, we evaluated this bioanalytical method by re-analysis of incurred samples as an additional measure of assay reproducibility. This method was successfully applied to a pharmacokinetic study in metastatic CRC patients enrolled in a genotype-guided phase Ib study of irinotecan administered in combination with 5-fluorouracil/leucovorin and bevacizumab.</p></div
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