Continuing trastuzumab beyond disease progression: outcomes analysis in patients with metastatic breast cancer

INTRODUCTION: We performed a retrospective analysis of HER2-overexpressing metastatic breast cancer patients to describe clinical outcomes of those who, despite progression of the disease (PD), maintained trastuzumab for multiple chemotherapy lines. We also compared survival of these patients with that of those who halted trastuzumab at first PD. METHODS: We identified 101 patients treated between July 2000 and January 2007. Nineteen were still receiving the first-line trastuzumab-based treatment without evidence of PD and were not included in this analysis. Of the remaining 82 patients, 59 retained trastuzumab for one or more additional lines of chemotherapy after PD, according to our institution policy. Twenty-three patients who changed treating institution and stopped trastuzumab at first progression were used as a control group. RESULTS: For patients retaining trastuzumab, the median follow-up was 39.6 months. Clinical outcomes showed the typical degradation between first and second lines of therapy which we would expect by halting trastuzumab at first progression. Response rates were 35\% and 16\% and median times to progression were 7.25 and 5.25 months for the first and second lines of trastuzumab therapy, respectively. The median overall survival (OS) rates were 70 months for patients who retained trastuzumab and 56 months for patients who halted the drug (hazard ratio [HR] 0.87, 95\% confidence interval [CI] 0.51 to 1.18; P = 0.52). If we consider OS from the start of trastuzumab therapy, the figures are 53.9 and 34.8 months, respectively (HR 0.78, 95\% CI 0.58 to 1.32; P = 0.2). CONCLUSION: A nonstatistically significant trend of improved survival for patients retaining trastuzumab is observed. This is in line with most retrospective analyses and recent randomized data. Retaining trastuzumab after progression is a reasonable option, but further randomized data are warranted to better define its role in comparison with other available options.

Contribuciones potenciales al bienestar humano de los mamíferos en Argentina

Mammals are key components of biodiversity mediating ecosystem functions, mainly because of the diversity of forms and functions of this group. Understanding and making explicit the role of mammals underpinning Nature's Contributions to People (NCP) or directly contributing to human well-being would help to influence policy formulation towards sustainable development and nature conservation. Through a workshop held at the XXXII Jornadas Argentinas de Mastozoología and subsequent collaborative work, we compiled information related to Mammal's Contributions to People in Argentina (MCP-Arg) based on participants' interpretation of the available literature and their field experience. Argentinian mammals contribute to 12 of the 18 defined NCPs. We derived numerous MCP-Arg from studies that focused mainly on ecological processes and conservation, revealing an information gap in MCP- Arg description, quantification, and mapping. All taxa contribute similarly to the overall contributions, highlighting the importance of preserving mammal diversity. Conservation should also be framed at the local community rather than regional scales, aiming to preserve ecological functioning and contributions to human well-being, especially within regulation contributions. Our results show destructive feedback between threats and habitat-related contributions, with habitat degradation being the greatest threat to mammalian contributions and habitat maintenance the most threatened one. Our research indicates that a substantial amount of knowledge about MCP-Arg is available through narratives and interpretations. Considering the NCP approach to mammalian research, we can make significant contributions to both mammal conservation and human well-being.Debido a su diversidad de formas y funciones, los mamíferos son componentes clave de la biodiversidad y cumplen importantes funciones ecosistémicas. Para formular políticas que permitan un desarrollo sostenible y la conservación de la naturaleza, es fundamental comprender y explicitar el papel de los mamíferos en sustentar las Contribuciones de la Naturaleza a las Personas (CNP). Durante un taller realizado en las XXXII Jornadas Argentinas de Mastozoología y un posterior estudio colaborativo, hemos recopilado información relacionada con las CNP de mamíferos en Argentina (CMP-Arg) en base a la interpretación de la literatura disponible y la experiencia de campo. En la Argentina, los mamíferos contribuyen en 12 de las 18 CNP definidas. Deducimos numerosas CMP-Arg de estudios centrados principalmente en procesos ecológicos y de conservación, que muestran un vacío de información en cuanto a descripción, cuantificación y mapeo de CMP-Arg. Todos los taxones realizan aportes similares a las contribuciones totales, lo que destaca la importancia de preservar la diversidad de mamíferos. Los esfuerzos de conservación deben enmarcarse no solo a escala regional, sino también a escala local, con el objetivo de preservar las CNP. Nuestros resultados han mostrado una asociación entre amenazas y contribuciones relacionadas con el hábitat: la degradación de este ha sido la principal amenaza para las contribuciones y su mantenimiento la contribución más amenazada. Nuestra investigación muestra que una cantidad importante de conocimiento sobre CMP-Arg está disponible a través de narrativas y representaciones sociales. Mediante la implementación del enfoque del CNP en la investigación mastozoológica, podemos hacer aportes significativos tanto para la conservación de los mamíferos como para el bienestar humano.Fil: Alonso Roldán, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; Argentina. Universidad Tecnologica Nacional. Facultad Regional Chubut. Grupo de Investigacion En Gestion, Desarrollo Territorial y Ambiente.; ArgentinaFil: Camino, Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Centro de Ecología Aplicada del Litoral. Universidad Nacional del Nordeste. Centro de Ecología Aplicada del Litoral; Argentina. Sociedad Zoológica de Londres; Reino Unido. Proyecto Quimilero; ArgentinaFil: Argoitia, María Antonella. Universidad Nacional del Nordeste; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Campos, Claudia Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; ArgentinaFil: Caruso, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Eder, Elena Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Baldi, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; Argentina. Wildlife Conservation Society; Estados UnidosFil: Birochio, Diego Enrique. Universidad Nacional de Rio Negro. Centro de Investigaciones y Transferencia de Rio Negro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Rio Negro; ArgentinaFil: Cappa, Flavio Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; ArgentinaFil: Lassaga, Maria Victoria. Universidad Nacional de Córdoba; Argentina. Natura International; ArgentinaFil: Olmedo, María Luz. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Programa de Investigación de Biodiversidad Argentina; Argentina. Programa de Conservación de los Murciélagos de Argentina; ArgentinaFil: Formoso, Anahí Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; Argentina. Universidad del Chubut; ArgentinaFil: D'agostino, Valeria Carina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: González Noschese, Camila Sofía. Programa de Conservación de los Murciélagos de Argentina; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Programa de Investigación de Biodiversidad Argentina; ArgentinaFil: Udrizar Sauthier, Daniel Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Juárez, Cecilia Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Formosa. Facultad de Recursos Naturales. Centro de Ecologia y Diversidad del Chaco.; ArgentinaFil: Degrati, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Iglesias, Martin. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Grupo de Estudios sobre Biodiversidad en Agroecosistemas; ArgentinaFil: Coelho, Lorena. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Sosa Drouville, Ailin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentina. Universidad Nacional del Comahue; ArgentinaFil: Priotto, Jose Waldemar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente; Argentin

World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

BACKGROUND: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. METHODS: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. FINDINGS: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629-0·741) to 0·833 (0·783-0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. INTERPRETATION: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. FUNDING: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

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

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

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011

Tiber Personal Rapid Transit

The project “Tiber Personal Rapid Transit” have been presented by the author at the Rome City Vision Competition1 2010, an ideas competition, which challenges architects, engineers, designers, students and creatives individuals to develop visionary urban proposals with the intention of stimulating and supporting the contemporary city, in this case Rome. The Tiber PRT proposal tries to answer the competition questions with the definition of a provocative idea: a Personal Rapid transit System on the Tiber river banks. The project is located in the central section of the Tiber river and aims at the renewal of the river banks with the insertion of a Personal Rapid Transit infrastructure. The project area include the riverbank of Tiber from Rome Transtevere RFI station to Piazza del Popolo, an area where main touristic and leisure attractions are located. The intervention area is actually no used by the city users and residents and constitute itself a strong barrier in the heart of the historic city

RICOSTRUZIONE MORFOLOGICA E RECUPERO AMBIENTALE DEI TORRENTI

Le attivit\ue0 connesse con il recupero ambientale dei corsi d'acqua richiedono un approccio multidisciplinare. La monografia si prefigge di fornire le principali conoscenze sulle peculiarit\ue0 morfologiche, sulla dinamica d'alveo e sulle sistemazioni idrauliche dei corsi d'acqua montani. Il lavoro si articola in quattro capitoli. Il primo capitolo tratta dei principali criteri di classificazione dei sistemi fluviali. Il secondo capitolo entra nella specifica classificazione morfologica dei torrenti alpini. Nel terzo capitolo viene presentata la teoria della 'ricostruzione morfologica' e la sua applicazione nella progettazione di opere di consolidamento in massi a basso impatto ambientale (step pool artificiali). Nell'ultimo capitolo \ue8 trattata la progettazione ed esecuzione delle briglie in legname e pietrame della tipologia a cassone