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

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

Discovery of novel and potent benzhydryl-tropane trypanocides highly selective for Trypanosoma cruzi

A benzhydryl tropinone oxime that is potently toxic to Trypanosoma cruzi has been previously identified. An SAR investigation determined that no part of the original compound was superfluous and all early SAR probes led to significant drops in activity. The only alteration that could be achieved without loss of activity was replacement of the aryl chloride substituent with chloro homologues. This led to the discovery of a trifluoromethyl-containing analogue with an EC50 against T. cruzi of 30 nM and a cytotoxicity selectivity index of over 1000 relative to rat skeletal myoblast L-6 cells

Comparative study of the grasshopper zoniopoda tarsata (romaLeide) and paulinia acuminata (Pauliniidae) based on chromosome and C-banding analysis

In most Acridoidea the basic karyotype is composed by 11 telocentric chromosomes and a telocentric X (2n=23, X0) in males and 12 telocentric chromosomes in females (2n=24, XX). In this paper we comparatively analyzed meiosis of Z. tarsata (Acrididae, Romaleinae) and P. acuminata (Pauliniidae) after C-banding and DAPI staining in order to investigate differences due to heterochromatin amount and localization. Z. tarsata and P. acuminata showed a karyotype composed by 11 somatic telocentric chromosomes and a telocentric X, corresponding to 2n=23, X0 diploid karyotype in males. After C-banding procedure Z. tarsata pachytene bivalents showed 12 densely stained spots including the X chromosome, 4 of these were observed in interstitial locations and the remaining in pericentric position of the telocentric bivalents. In P. acuminata 4 C-banded spots were observed, 2 of these in interstitial locations and the remaining in pericentric position. After pachytene DAPI staining, bivalents showed specific bright stained areas corresponding to those detected after C-banding in Z. tarsata, the same was observed in P. acuminata. These differences demonstrate that despite chromosome similarity between these taxa heterochromatin evolution seems to follow a different path, allowing a clear differentiation between these two karyotypes

Comparative study of the grasshopper zoniopoda tarsata (romaLeide) and paulinia acuminata (Pauliniidae) based on chromosome and C-banding analysis

In most Acridoidea the basic karyotype is composed by 11 telocentric chromosomes and a telocentric X (2n=23, X0) in males and 12 telocentric chromosomes in females (2n=24, XX). In this paper we comparatively analyzed meiosis of Z. tarsata (Acrididae, Romaleinae) and P. acuminata (Pauliniidae) after C-banding and DAPI staining in order to investigate differences due to heterochromatin amount and localization. Z. tarsata and P. acuminata showed a karyotype composed by 11 somatic telocentric chromosomes and a telocentric X, corresponding to 2n=23, X0 diploid karyotype in males. After C-banding procedure Z. tarsata pachytene bivalents showed 12 densely stained spots including the X chromosome, 4 of these were observed in interstitial locations and the remaining in pericentric position of the telocentric bivalents. In P. acuminata 4 C-banded spots were observed, 2 of these in interstitial locations and the remaining in pericentric position. After pachytene DAPI staining, bivalents showed specific bright stained areas corresponding to those detected after C-banding in Z. tarsata, the same was observed in P. acuminata. These differences demonstrate that despite chromosome similarity between these taxa heterochromatin evolution seems to follow a different path, allowing a clear differentiation between these two karyotypes

Choice of second-line systemic therapy in stage IV small cell lung cancer (SCLC) - A decision-making analysis amongst European lung cancer experts.

OBJECTIVES Stage IV small cell lung cancer (SCLC) is associated with short survival and progression after first-line systemic therapy frequently occurs within months. Although topotecan is approved for second-line treatment, its efficacy is limited, and treatment heterogeneity exists. MATERIAL AND METHODS The decision-making patterns for second line treatment of 13 European medical oncologists with expertise in SCLC were analyzed. RESULTS The two criteria most relevant to decision-making were the performance status and the interval of recurrence since first-line treatment. With an interval of less than 3 months since the end of first-line chemotherapy, 62 % of the experts recommended cyclophosphamide, doxorubicin and vincristine (CAV) for fit patients and 54 % recommended topotecan for unfit patients. For an interval of more than 6 months, a clear consensus for a re-challenge with a platinum doublet was achieved (92 %). However, there was no consensus on the second-line therapy with an interval of 3-6 months since the end of first-line therapy. CONCLUSION Real world practice may differ from recommendations in general guidelines and cannot always be directly derived from trial results as other factor such as habits, patient's preference, convenience or costs have to be factored in

Treatment of brain metastases in small cell lung cancer: Decision-making amongst a multidisciplinary panel of European experts

BACKGROUND Brain metastases (BM) are common in patients with small cell lung cancer (SCLC). In recent years, the role of whole brain radiotherapy (WBRT) for brain metastases in lung cancer is being reevaluated, especially in the context of new systemic treatments available for SCLC. With this analysis, we investigate decision-making in SCLC patients with BM among European experts in medical oncology and radiation oncology. METHODS We analyzed decision-making from 13 medical oncologists (selected by IASLC) and 13 radiation oncologists (selected by ESTRO) specialized in SCLC. Management strategies of individual experts were converted into decision trees and analyzed for consensus. RESULTS AND CONCLUSION In asymptomatic patients, chemotherapy alone is the most commonly recommended first line treatment. In asymptomatic patients with limited volume of brain metastases, a higher preference for chemotherapy without WBRT among medical oncologists compared to radiation oncologists was observed. For symptomatic patients, WBRT followed by chemotherapy was recommended most commonly. For limited extent of BM in symptomatic patients, some experts chose stereotactic radiotherapy as an alternative to WBRT. Significant variation in clinical decision-making was observed among European SCLC experts for the first line treatment of patients with SCLC and BM

Randomized Phase III Trial of Erlotinib versus Docetaxel in Patients with Advanced Squamous Cell Non–Small Cell Lung Cancer Failing First-Line Platinum-Based Doublet Chemotherapy Stratified by VeriStrat Good versus VeriStrat Poor. The European Thoracic Oncology Platform (ETOP) EMPHASIS-lung Trial

Introduction Docetaxel and erlotinib are registered second-line treatments for wild-type EGFR NSCLC. Previous studies suggested a predictive value of the VeriStrat test in second-line therapy of NSCLC, classifying patients as either VeriStrat good or VeriStrat poor. EMPHASIS-lung aimed at exploring this predictive effect in patients with squamous cell NSCLC. The trial closed prematurely because of low accrual and results from other trials. Our analysis includes an exploratory combined analysis with results from the PROSE trial. Methods EMPHASIS-lung was a randomized phase III multicenter trial exploring the differential effect of second-line erlotinib versus docetaxel on progression-free survival (PFS) in VeriStrat good versus VeriStrat poor patients with squamous cell NSCLC. Results A total of 80 patients were randomized, with 72.5% categorized as VeriStrat good. Patient characteristics were balanced between VeriStrat status and treatment groups. The median PFS times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 4.1 and 1.6 months, respectively, versus 1.9 and 2.1 months, respectively, in the VeriStrat poor cohort. The median overall survival (OS) times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 7.8 and 8.4 months, respectively, and 4.4 and 5.2 months, respectively, in the VeriStrat poor cohort. An additional exploratory analysis was performed; in it, 47 patients from the squamous cell subgroup of PROSE were included in a combined analysis, contributing with 45 PFS and 41 OS events. Conclusions The final analysis of EMPHASIS-lung did not show a differential effect on PFS for erlotinib versus docetaxel stratified by VeriStrat status. Similarly, in the combined analysis, no significant treatment by VeriStrat status interaction was observed (interaction p = 0.24 for PFS and 0.45 for OS, stratified by study). © 2017 International Association for the Study of Lung Cance