A phase II trial of bryostatin 1 in patients with non-Hodgkin's lymphoma

Bryostatin 1 is a naturally occurring macrocyclic lactone with promising antitumour and immunomodulatory function in preclinical and phase I clinical investigations. In this phase II study, 17 patients with progressive non-Hodgkin's lymphoma of indolent type (NHL), previously treated with chemotherapy, received a median of 6 (range 1–9) intravenous infusions of 25 μg/m2bryostatin 1 given once weekly over 24 hours. In 14 evaluable patients no responses were seen. Stable disease was attained in one patient for 9 months. The principal toxicities were myalgia and phlebitis. Treatment was discontinued early because of toxicity alone (phlebitis) in 2 patients, toxicity in addition to progressive disease in 3 patients (myalgia and phlebitis n = 2; thrombocytopenia n = 1) and progressive disease in 5 patients. The results fail to demonstrate efficacy of this regimen of bryostatin 1 in the treatment of NHL. In light of preclinical data that demonstrate synergy between bryostatin 1 and several cytotoxic agents and cytokines, clinical studies to investigate bryostatin 1 in combination are warranted. We also present data to demonstrate that central venous lines may be used in future studies to avoid phlebitis. © 2001 Cancer Research Campaign http://www.bjcancer.co

Vulnerability of drug‐resistant EML4‐ALK rearranged lung cancer to transcriptional inhibition

A subset of lung adenocarcinomas is driven by the EML4‐ALK translocation. Even though ALK inhibitors in the clinic lead to excellent initial responses, acquired resistance to these inhibitors due to on‐target mutations or parallel pathway alterations is a major clinical challenge. Exploring these mechanisms of resistance, we found that EML4‐ALK cells parental or resistant to crizotinib, ceritinib or alectinib are remarkably sensitive to inhibition of CDK7/12 with THZ1 and CDK9 with alvocidib or dinaciclib. These compounds robustly induce apoptosis through transcriptional inhibition and downregulation of anti‐apoptotic genes. Importantly, alvocidib reduced tumour progression in xenograft mouse models. In summary, our study takes advantage of the transcriptional addiction hypothesis to propose a new treatment strategy for a subset of patients with acquired resistance to first‐, second‐ and third‐generation ALK inhibitors

Clinical expert guidelines for the management of cough in lung cancer: report of a UK task group on cough

Background Cough is a common and distressing symptom in lung cancer patients. The clinical management of cough in lung cancer patients is suboptimal with limited high quality research evidence available. The aim of the present paper is to present a clinical guideline developed in the UK through scrutiny of the literature and expert opinion, in order to aid decision making in clinicians and highlight good practice. Methods Two systematic reviews, one focusing on the management of cough in respiratory illness and one Cochrane review specifically on cancer, were conducted. Also, data from reviews, phase II trials and case studies were synthesized. A panel of experts in the field was also convened in an expert consensus meeting to make sense of the data and make clinical propositions. Results A pyramid of cough management was developed, starting with the treatment of reversible causes of cough/specific pathology. Initial cough management should focus on peripherally acting and intermittent treatment; more resistant symptoms require the addition of (or replacement by) centrally acting and continuous treatment. The pyramid for the symptomatic management starts from the simpler and most practical regimens (demulcents, simple linctus) to weak opioids to morphine and methadone before considering less well-researched and experimental approaches. Conclusion The clinical guidelines presented aim to provide a sensible clinical approach to the management of cough in lung cancer. High quality research in this field is urgently required to provide more evidence-based recommendations

Bases epidemiológicas y estrategias de sanitización de sarna en pera William's en el alto valle de Rio Negro y Neuquén

Con el propósito de vislumbrar el comportamiento de la sarna de peral causada por Venturia pirina, y avanzar en el manejo de la enfermedad en la región (Río Negro y Neuquén), los objetivos de este estudio fueron: (i) Evaluar la liberación y captura de esporas en relación a las condiciones climáticas (CC) y presencia de síntomas de la enfermedad, en dos huertos comerciales de pera William’s con antecedentes, y (ii) comparar la degradación de hojarasca entera y triturada en combinación con urea y bioformulados i.a. Trichoderma, como estrategia de sanitización. Las CC y capturas se monitorearon durante septiembre a diciembre 2022. La captura de ascosporas se registró con eventos de rocío, precipitaciones y horas de hoja mojada, aumentado la incidencia de la enfermedad en enero, resultando los conidios el principal inóculo. La degradación de hojarasca evaluada de junio a octubre 2022 como pérdida de peso (%) a los 60, 90 y 120 días de inicio del ensayo, fue significativamente mayor con la trituración para todas las combinaciones.Fil: Vexenat De Giorgi, Leticia. Universidad Nacional del Comahue. Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue; Argentina.Fil: Vexenat De Giorgi, Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Lutz, M. Cecilia. Universidad Nacional del Comahue. Facultad de Ciencias Agrarias; Argentina.Fil: Lutz, M. Cecilia. Universidad Nacional del Comahue. Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue; Argentina.Fil: Lutz, M. Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Reyes, Fernanda. Universidad Nacional del Comahue. Instituto deTierras, Agua y Medio Ambiente; Argentina.Fil: Reyes, Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Basso, Carla N. Universidad Nacional del Comahue. Facultad de Ciencias Agrarias; Argentina.Fil: Basso, Carla N. Universidad Nacional del Comahue. Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue; Argentina.Fil: Basso, Carla N. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Blackhall, Valeria. Universidad Nacional del Comahue. Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue; Argentina.Fil: Blackhall, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Sosa, M. Cristina. Universidad Nacional del Comahue. Facultad de Ciencias Agrarias; Argentina.Fil: Sosa, M. Cristina. Universidad Nacional del Comahue. Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue; Argentina.Fil: Sosa, M. Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

The State of the World’s Urban Ecosystems: what can we learn from trees, fungi and bees?

Trees are a foundation for biodiversity in urban ecosystems and therefore must be able to withstand global change and biological challenges over decades and even centuries to prevent urban ecosystems from deteriorating. Tree quality and diversity should be prioritized over simply numbers to optimize resilience to these challenges. Successful establishment and renewal of trees in cities must also consider belowground (e.g., mycorrhizas) and aboveground (e.g., pollinators) interactions to ensure urban ecosystem longevity, biodiversity conservation and continued provision of the full range of ecosystem services provided by trees. Positive interactions with nature inspire people to live more sustainable lifestyles that are consistent with stopping biodiversity loss and to participate in conservation actions such as tree‐planting and supporting pollinators. Interacting with nature simultaneously provides mental and physical health benefits to people. Since most people live in cities, here we argue that urban ecosystems provide important opportunities for increasing engagement with nature and educating people about biodiversity conservation. While advocacy on biodiversity must communicate in language that is relevant to a diverse audience, over‐simplified messaging, may result in unintended negative outcomes. For example, tree planting actions typically focus on numbers rather than diversity while the call to save bees has inspired unsustainable proliferation of urban beekeeping that may damage wild bee conservation through increased competition for limited forage in cities and disease spread. Ultimately multiple ecosystem services must be considered (and measured) to optimize their delivery in urban ecosystems and messaging to promote the value of nature in cities must be made widely available and more clearly defined

Preventing species extinctions: A global conservation consortium for Erica

Societal Impact Statement Human-caused habitat destruction and transformation is resulting in a cascade of impacts to biological diversity, of which arguably the most fundamental is species extinctions. The Global Conservation Consortia (GCC) are a means to pool efforts and expertise across national boundaries and between disciplines in the attempt to prevent such losses in focal plant groups. GCC Erica coordinates an international response to extinction threats in one such group, the heaths, or heathers, of which hundreds of species are found only in South Africa's spectacularly diverse Cape Floristic Region. Summary Effectively combating the biodiversity crisis requires coordinated conservation efforts. Botanic Gardens Conservation International (BGCI) and numerous partners have established Global Conservation Consortia (GCC) to collaboratively develop and implement comprehensive conservation strategies for priority threatened plant groups. Through these networks, institutions with specialised collections and staff can leverage ongoing work to optimise impact for threatened plant species. The genus Erica poses a challenge similar in scale to that of the largest other GCC group, Rhododendron, but almost 700 of the around 800 known species of Erica are concentrated in a single biodiversity hotspot, the Cape Floristic Region (CFR) of South Africa. Many species are known to be threatened, suffering the immediate impacts of habitat destruction, invasive species, changes in natural fire regimes and climate change. Efforts to counter these threats face general challenges: disproportionate burden of in situ conservation falling on a minority of the community, limited knowledge of species-rich groups, shortfalls in assessing and monitoring threat, lack of resources for in situ and limitations of knowledge for ex situ conservation efforts and in communicating the value of biological diversity to a public who may never encounter it in the wild. GCC Erica brings together the world's Erica experts, conservationists and the botanical community, including botanic gardens, seed banks and organisations in Africa, Madagascar, Europe, the United States, Australia and beyond. We are collaboratively pooling our unique sets of skills and resources to address these challenges in working groups for conservation prioritisation, conservation in situ, horticulture, seed banking, systematic research and outreach.publishedVersio

EPAC-Lung:Pooled analysis of circulating tumor cells in advanced non-small cell lung cancer

Background: We assessed the clinical validity of circulating tumor cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a European pooled analysis of individual patient data. This is the largest study of its kind and the first to examine between-centre heterogeneity of CTC identification in NSCLC.Methods: Nine European NSCLC CTC centers were asked to provide reported/unreported anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 - March 2017. We used Cox regression models, stratified by centre, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinico-pathological models using likelihood ratio (LR) statistics and c-indices.Results: Seven out of nine eligible centers provided data for 550 eligible patients, including 209 patients whose prognostic information was previously unpublished. CTC counts of ≥ 2 and ≥5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: HR 1.72, p < 0·001; ≥5 CTCs: HR 2.21, p < 0·001) and overall survival (≥2 CTCs: HR 2·18, p < 0·001; ≥5 CTCs: HR 2·75, p < 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinico-pathological models (log-transformed CTCs p < 0·0001; ≥2 CTCs p < 0·0001; ≥5 CTCs p < 0·0001), while more moderate improvements were observed with the use of c-index models. There was minor evidence of between-center heterogeneity in the effect on PFS, but not OS.No difference in CTC profile was observed between key NSCLC molecular subsets such as EGFR, ALK, and KRAS.Conclusions: These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC. CTC count improves prognostication when added to full clinico-pathological predictive models. ≥2 CTCs is an appropriate cutoff to move towards establishing clinical utility

Anti-fibrinolytic agents in post partum haemorrhage: a systematic review

BACKGROUND: Post partum haemorrhage is a leading cause of maternal death worldwide. It also contributes to maternal morbidity as women may require a hysterectomy to control bleeding, or may require a blood transfusion, which can transmit viral infections. Anti-fibrinolytic agents have been proposed as a treatment for post partum haemorrhage. We conducted a systematic review to assess the effectiveness and safety of anti-fibrinolytic agents in post partum bleeding. METHODS: All randomised controlled trials of anti-fibrinolytic agents given for bleeding during the postpartum period were included in this review. We searched Medline, PubMed, EMBASE, Cochrane Central Register of Controlled trials, Web of Science, metaRegister of controlled trials, LILACS, Reproductive Health Library, African healthline, POPLINE, MedCarib, CINAHL, Clinicaltrials.gov and the reference lists of eligible trials. Two authors extracted data. Methodological quality was assessed by evaluating allocation concealment. The primary outcome was maternal mortality. Secondary outcomes were blood loss, blood transfusion, hysterectomy, mean haemoglobin concentration, thrombo-embolic events and other adverse effects. RESULTS: We identified three randomised controlled trials involving 461 participants. The trials compared tranexamic acid with no treatment and reported blood loss after delivery. In all three trials, allocation concealment was either inadequate or unclear. The administration of tranexamic acid was associated with a reduction in blood loss of 92 millilitres (95%CI 76 to 109). The most frequently reported adverse effect of tranexamic acid was nausea, although the increase was easily compatible with the play of chance (RR 4.63, 95%CI 0.23 to 95.14). CONCLUSION: Tranexamic acid may reduce blood loss in post partum haemorrhage. However, the quality of the currently available evidence is poor. Adequately powered, high quality randomised controlled trials are needed