The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

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

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

A new infrageneric classification of Mucuna (Leguminosae-Papilionoideae): supported by morphology, molecular phylogeny and biogeography

The previous infrageneric classification of Mucuna (Leguminosae, Papilionoideae) recognized two subgenera, M. subg. Mucuna and M. subg. Stizolobium, but that classification is not supported fully by molecular phylogenetic analyses, which reveal three main clades in Mucuna (rather than the traditional two). A new taxon M. subg. Macrocarpa is proposed based on the results of a molecular phylogenetic analysis, supported by fruit characters and biogeography. Historically, the representatives of this new subgenus were considered as members of M. subg. Mucuna, but species of subgenus Macrocarpa differ from species of the other two subgenera by their longer ovaries containing a higher number of ovules and, consequently, longer pods containing more seeds, and by the different fruit length to width ratio. This study presents a new infrageneric classification of the genus Mucuna. The six species of M. subg. Macrocarpa are reviewed, and species descriptions, typifications (including five new lectotypes), a distribution map, and a species identification key are presented413606616CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP245590/2012-92012/04635-

Eriosema hatschbachii (Leguminosae, Papilionoideae), a new species from Minas Gerais, Brazil.

Eriosema hatschbachii, a new species of Leguminosae (Papilionoideae) from Minas Gerais, Brazil, is described and illustrated. The taxon is morphologically similar to E. floribundum Benth. and E. pycnanthum Benth. var. pycnanthum, but differs mainly in having many parallel secondary veins on the leaflets (similar to the venation seen on nearly all species of the genus Tephrosia) and erect stems with leaves only near the apex

Molecular phylogenetic insights into the evolution of Eriosema (Fabaceae):a recent tropical savanna-adapted genus

Eriosema comprises c. 150 species and has a pantropical distribution and two centres of diversity, Africa and America. The species occur in tropical savannas and grasslands, including the cerrado in Brazil. They have adapted to these environments by developing specialized underground organs, and an abundance of trichomes. Here we present the first comprehensive molecular phylogenetic analysis of Eriosema, including species from its entire distribution range and generating 391 new DNA sequences. We sampled 140 species from nine genera of Cajaninae, of which 94 (60% of the genus) were Eriosema. Our analyses were based on the nuclear ITS and plastid rpl32 and trnQ regions, and used maximum likelihood and Bayesian phylogenetic analyses of individual and combined data sets. In all analyses, Eriosema was resolved as monophyletic, but its interspecific relationships are not well resolved. Rhynchosia is not monophyletic, and some African Rhynchosia spp. emerged together as sister to Eriosema. Our study supports the monophyly of Adenodolichos, Dunbaria, Flemingia and Cajanus, but Chrysoscias and Bolusafra formed a clade that is sister to a group of Rhynchosia spp. Paracalyx was resolved as paraphyletic and nested among African Rhynchosia spp. Divergence time analysis suggested that the Eriosema lineages diverged 6.5–10.7 Mya. Two major lineages have diversified in Eriosema, one including most of the African species (4.41–6.68 Mya), the other mainly composed of the South American cerrado species (3.56–5.78 Mya). These results revealed that Eriosema is a recent and tropical savanna-adapted group, and its diversification occurred in the late Miocene in parallel with the expansion of C4 grasslands