Near-infrared quantum dots labelled with a tumor selective tetrabranched peptide for in vivo imaging

Near-infrared quantum dots (NIR QDs) are a new class of fluorescent labels with excellent bioimaging features, such as high fluorescence intensity, good fluorescence stability, sufficient electron density, and strong tissue-penetrating ability. For all such features, NIR QDs have great potential for early cancer diagnosis, in vivo tumor imaging and high resolution electron microscopy studies on cancer cells

Development and validation of the ID-EC - The ITALIAN version of the identify chronic migraine

Background: Case-finding tools, such as the Identify Chronic Migraine (ID-CM) questionnaire, can improve detection of CM and alleviate its significant societal burden. We aimed to develop and validate the Italian version of the ID-CM (ID-EC) in paper and as a smart app version in a headache clinic-based setting. Methods: The study investigators translated and adapted to the Italian language the original ID-CM questionnaire (ID-EC) and further implemented it as a smart app. The ID-EC was tested in its paper and electronic version in consecutive patients referring to 9 Italian tertiary headache centers for their first in-person visit. The scoring algorithm of the ID-EC paper version was applied by the study investigators (case-finding) and by patients (self-diagnosis), while the smart app provided to patients automatically the diagnosis. Diagnostic accuracy of the ID-EC was assessed by matching the questionnaire results with the interview-based diagnoses performed by the headache specialists during the visit according to the criteria of International Classification of Headache Disorders, III edition, beta version. Results: We enrolled 531 patients in the test of the paper version of ID-EC and 427 in the validation study of the smart app. According to the clinical diagnosis 209 patients had CM in the paper version study and 202 had CM in the smart app study. 79.5% of patients returned valid paper questionnaires, while 100% of patients returned valid and complete smart app questionnaires. The paper questionnaire had a 81.5% sensitivity and a 81.1% specificity for case-finding and a 30.7% sensitivity and 90.7% specificity for self-diagnosis, while the smart app had a 64.9% sensitivity and 90.2% specificity. Conclusions: Our data suggest that the ID-EC, developed and validated in tertiary headache centers, is a valid case-finding tool for CM, with sensitivity and specificity values above 80% in paper form, while the ID-EC smart app is more useful to exclude CM diagnosis in case of a negative result. Further studies are warranted to assess the diagnostic accuracy of the ID-EC in general practice and population-based settings

Investigations into the killing activity of an antimicrobial peptide active against extensively antibiotic-resistant K. pneumoniae and P. aeruginosa

SET-M33 is a multimeric antimicrobial peptide active against Gram-negative bacteria in vitro and in vivo. Insights into its killing mechanism could elucidate correlations with selectivity. SET-M33 showed concentration-dependent bactericidal activity against colistin-susceptible and resistant isolates of P. aeruginosa and K. pneumoniae. Scanning and transmission microscopy studies showed that SET-M33 generated cell blisters, blebs, membrane stacks and deep craters in K. pneumoniae and P. aeruginosa cells. NMR analysis and CD spectra in the presence of sodium dodecyl sulfate micelles showed a transition from an unstructured state to a stable α-helix, driving the peptide to arrange itself on the surface of micelles. SET-M33 kills Gram-negative bacteria after an initial interaction with bacterial LPS. The molecule becomes then embedded in the outer membrane surface, thereby impairing cell function. This activity of SET-M33, in contrast to other similar antimicrobial peptides such as colistin, does not generate resistant mutants after 24h of exposure, non-specific interactions or toxicity against eukaryotic cell membranes, suggesting that SET-M33 is a promising new option for the treatment of Gram-negative antibiotic-resistant infections

Systematic versus on-demand early palliative care: results from a multicentre, randomised clinical trial

Background Early palliative care (EPC) in oncology has been shown to have a positive impact on clinical outcome, quality-of-care outcomes, and costs. However, the optimal way for activating EPC has yet to be defined. Methods This prospective, multicentre, randomised study was conducted on 207 outpatients with metastatic or locally advanced inoperable pancreatic cancer. Patients were randomised to receive ‘standard cancer care plus on-demand EPC’ (n = 100) or ‘standard cancer care plus systematic EPC’ (n = 107). Primary outcome was change in quality of life (QoL) evaluated through the Functional Assessment of Cancer Therapy – Hepatobiliary questionnaire between baseline (T0) and after 12 weeks (T1), in particular the integration of physical, functional, and Hepatic Cancer Subscale (HCS) combined in the Trial Outcome Index (TOI). Patient mood, survival, relatives' satisfaction with care, and indicators of aggressiveness of care were also evaluated. Findings The mean changes in TOI score and HCS score between T0 and T1 were −4.47 and −0.63, with a difference between groups of 3.83 (95% confidence interval [CI] 0.10–7.57) (p = 0.041), and −2.23 and 0.28 (difference between groups of 2.51, 95% CI 0.40–4.61, p = 0.013), in favour of interventional group. QoL scores at T1 of TOI scale and HCS were 84.4 versus 78.1 (p = 0.022) and 52.0 versus 48.2 (p = 0.008), respectively, for interventional and standard arm. Until February 2016, 143 (76.9%) of the 186 evaluable patients had died. There was no difference in overall survival between treatment arms. Interpretations Systematic EPC in advanced pancreatic cancer patients significantly improved QoL with respect to on-demand EPC

Programa intensivo ERASMUS: TOPCART. Documentación Geométrica del Patrimonio (memoria de actividades 2010-2011)

[EN] Data contained in this record come from the following accademic activity (from which it is possible to locate additional records related with the Monastery):● LDGP_inv_002: "Intensive Program ERASMUS: TOPCART. Geometric Documentation of the Heritage (administrative and academic documentation)", http://hdl.handle.net/10810/9906[ES] Los datos de este registro provienen de la una actividad académica que también aparece descrita en el repositorio y desde donde se puede acceder a otros trabajos relacionados con el Monasterio:● LDGP_inv_002: "Programa intensivo ERASMUS: TOPCART. Documentación Geométrica del Patrimonio (documentación administrativa y académica)", http://hdl.handle.net/10810/9906[EN] The main objective this project is looking for is the exchange of practical methodologies, in topics related with the measure and representation of heritage, between teachers and specially students from different countries. For the achievement of this aim we expect the participation of a group of about 30 students and 8 lecturers from Germany, Italy, Greece, Lithuania and Spain.Activities will be focused on the development of concrete projects in documentation of heritage, specifically in the San Prudencio Monastery (La Rioja, Spain). In this site, digital techniques for the acquisition of geometric information from GPS equipment, surveying total stations, laser scanner and photogrammetry systems, will be put into practice.Obtained data will be processed as follows: first of all, they will be documented by adding necessary metadata in order to ensure their use in the future, then, they will be treated to obtain cartographic representations and virtual models which can be distributed on the Internet.As results we expect: metric data of the monument, graphic models for difussion and collaboration partnertships.[ES] El objetivo principal que se persigue en este proyecto es el intercambio de metodológico práctico, en materias afines a la medida y la representación del patrimonio, entre profesores y fundamentalmente alumnos, de diferentes países. Para la consecución de este fin se espera la participación de un grupo de aproximadamente 25 alumnos y 8 profesores de (Alemania, Italia, Grecia, Lituania y España).Las actividades se centrarán en el desarrollo de proyectos concretos de documentación de elementos patrimoniales, en concreto el apartado práctico se desarrollará en el Monasterio de San Prudencio (La Rioja, España). En el se aplicarán técnicas digitales de registro de información geométrica, constituidas por receptores GPS, estaciones totales topográficas, escáneres láser y sistemas fotogramétricos.Los datos obtenidos serán tratados de la siguiente manera: en primer lugar serán documentados, mediante la adición de la metainformación necesaria para garantizar su utilidad a lo largo del tiempo, seguidamente serán procesados con el fin de obtener las representaciones cartográficas y modelos virtuales de representación que puedan ser difundidas por medio de Internet.Como resultados se pretenden: un conjunto de registros métricos del momento de la intervención, modelos gráficos de difusión y finalmente relaciones de colaboración interpersonal e interinstitucional.European Commission, DG Education and Culture (Erasmus 2009-1-ES1-ERAIP-0013, 2010-1-ES1-ERA10-0024); Organismo Autónomo Programas Educativos Europeos (OAPEE); Gobierno de La Rioja (Spain); Universidad de La Rioja; Clavijo City Council; Logroño City Council; Ilustre Colegio de Ingenieros Técnicos en Topografía (Delegación de La Rioja)[ES] Memoria de proyecto (PDF) [es el último fichero de la lista, el enlace directo es https://addi.ehu.es/bitstream/10810/7053/1053/ldgp_mem011-1_Clavijo_SanPrudencio.pdf] + 11 imágenes de la visita preliminar en abril de 2009, en formato JPEG + 19 nubes de puntos en formato txt (comprimido en ZIP junto a un fichero de metadatos y una imagen que sirve de croquis y que también se presenta suelta) + 27 fotografías tomadas desde un helicóptero radicontrolado en 2011 por el grupo H (JPEG) + 18 fotografías métricas del edificio en forma de -L- tomadas desde el Sur + 13 fotografías métricas del edificio en forma de -L- tomadas desde el Este + 95 fotografías métricas del interior del edificio en forma de -L- (JPEG) + 35 fotografías métricas tomadas desde el cerro que se encuentra al sur (JPEG) + 8 fotografías métricas que forman 4 pares estereoscópicos (2 del grupo B y 2 del grupo D) (JPEG) + 183 fotografías métricas que forman 91 tripletas (grupos B, C y D) (JPEG). [NOTA: este registro no está cerrado, se irán incorporando nuevos materiales de forma progresiva][EN] General report (PDF) [it is the last file of the list, the direct link is https://addi.ehu.es/bitstream/10810/7053/1053/ldgp_mem011-1_Clavijo_SanPrudencio.pdf] + 11 pictures taken during the preliminary visit in April 2009 (JPEG format) + 19 point clouds in plain text (compressed in a ZIP file together with a file with metadata and an image PNG as sketch, these image are also presented on their own) + 27 photographs taken from a remote-controlled helicopter for the group H in 2011(JPEG) + 18 metric pictures of the L-shaped building taken from the South (JPEG) + 13 metric pictures of the L-shaped building taken from the East (JPEG) + 95 metric pictures of the inside part of the L-shaped building (JPEG) + 35 metric photographs taken from the hill opposite in the Southern + 8 metric photographs in four stereopairs (2 from group B and 2 from group D) (JPEG) + 183 metric photographs arranged in 91 triplets from groups B, C and D (JPEG). [NOTE: this record is not closed, more data will be uploaded progressively

Suitability of external controls for drug evaluation in Duchenne muscular dystrophy

OBJECTIVE: To evaluate the suitability of real-world data (RWD) and natural history data (NHD) for use as external controls in drug evaluations for ambulatory Duchenne muscular dystrophy (DMD). METHODS: The consistency of changes in the 6-minute walk distance (Δ6MWD) was assessed across multiple clinical trial placebo arms and sources of NHD/RWD. Six placebo arms reporting 48-week Δ6MWD were identified via literature review and represented 4 sets of inclusion/exclusion criteria (n = 383 patients in total). Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total). Mean Δ6MWD was compared between each placebo arm and RWD/NHD source after subjecting the latter to the inclusion/exclusion criteria of the trial for baseline age, ambulatory function, and steroid use. Baseline covariate adjustment was investigated in a subset of patients with available data. RESULTS: Analyses included ∼1,200 patient-years of follow-up. Differences in mean Δ6MWD between trial placebo arms and RWD/NHD cohorts ranged from -19.4 m (i.e., better outcomes in RWD/NHD) to 19.5 m (i.e., worse outcomes in RWD/NHD) and were not statistically significant before or after covariate adjustment. CONCLUSIONS: We found that Δ6MWD was consistent between placebo arms and RWD/NHD subjected to equivalent inclusion/exclusion criteria. No evidence for systematic bias was detected. These findings are encouraging for the use of RWD/NHD to augment, or possibly replace, placebo controls in DMD trials. Multi-institution collaboration through the Collaborative Trajectory Analysis Project rendered this study feasible

Severe asthma: One disease and multiple definitions

Introduction: There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used. Thus, according to the parameters chosen, each patient may result in having severe asthma or not. The aim of this study was to evaluate how the choice of a specific definition of severe asthma can change the allocation of patients. Methods: Data collected from the Severe Asthma Network Italy (SANI) registry were analyzed. All the patients included were then reclassified according to the definitions of U-BIOPRED, NICE, WHO, ATS/ERS, GINA, ENFUMOSA, and TENOR. Results: 540 patients, were extracted from the SANI database. We observed that 462 (86%) met the ATS/ERS criteria as well as the GINA criteria, 259 (48%) the U-Biopred, 222 (41%) the NICE, 125 (23%) the WHO, 313 (58%) the Enfumosa, and 251 (46%) the TENOR criteria. The mean eosinophil value were similar in the ATS/ERS, U-Biopred, and Enfumosa (528, 532 and 516 cells/mcl), higher in WHO and Tenor (567 and 570 cells/mcl) and much higher in the NICE classification (624 cells/mcl). Lung function tests resulted similarly in all groups, with WHO (67%) and ATS/ERS-GINA (73%), respectively, showing the lower and upper mean FEV1 values. Conclusions: The present observations clearly evidence the heterogeneity in the distribution of patients when different definitions of severe asthma are used. However, the recent definition of severe asthma, provided by the GINA document, is similar to that indicated in 2014 by ATS/ERS, allowing mirror reclassification of the patients examined. This lack of homogeneity could complicate the access to biological therapies. The definition provided by the GINA document, which reflects what suggested by ATS/ERS, could partially overcome the problem

Insight from an Italian Delphi Consensus on EVAR feasibility outside the instruction for use: the SAFE EVAR Study

BACKGROUND: The SAfety and FEasibility of standard EVAR outside the instruction for use (SAFE-EVAR) Study was designed to define the attitude of Italian vascular surgeons towards the use of standard endovascular repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA) outside the instruction for use (IFU) through a Delphi consensus endorsed by the Italian Society of Vascular and Endovascular Surgery (Societa Italiana di Chirurgia Vascolare ed Endovascolare - SICVE). METHODS: A questionnaire consisting of 26 statements was developed, validated by an 18 -member Advisory Board, and then sent to 600 Italian vascular surgeons. The Delphi process was structured in three subsequent rounds which took place between April and June 2023. In the first two rounds, respondents could indicate one of the following five degrees of agreement: 1) strongly agree; 2) partially agree; 3) neither agree nor disagree; 4) partially disagree; 5) strongly disagree; while in the third round only three different choices were proposed: 1) agree; 2) neither agree nor disagree; 3) disagree. We considered the consensus reached when >70% of respondents agreed on one of the options. After the conclusion of each round, a report describing the percentage distribution of the answers was sent to all the participants. RESULTS: Two -hundred -forty-four (40.6%) Italian Vascular Surgeons agreed to participate the first round of the Delphi Consensus; the second and the third rounds of the Delphi collected 230 responders (94.3% of the first -round responders). Four statements (15.4%) reached a consensus in the first rounds. Among the 22 remaining statements, one more consensus (3.8%) was achieved in the second round. Finally, seven more statements (26.9%) reached a consensus in the simplified last round. Globally, a consensus was reached for almost half of the proposed statements (46.1%). CONCLUSIONS: The relatively low consensus rate obtained in this Delphi seems to confirm the discrepancy between Guideline recommendations and daily clinical practice. The data collected could represent the source for a possible guidelines' revision and the proposal of specific Good Practice Points in all those aspects with only little evidence available